Systemic Sclerosis
Conditions
Brief summary
This study will assess the efficacy and safety of tocilizumab compared with placebo in participants with SSc across approximately 120 planned global study sites. The study will consist of a 48-week, double-blind, placebo-controlled period followed by a 48-week open-label treatment period. Participants will be assigned, in a 1:1 ratio, to double-blind treatment with active tocilizumab or matching placebo. In the open-label period, eligible participants from either arm may receive active tocilizumab.
Interventions
DRUGPlacebo
Participants will receive matching placebo subcutaneous (SC) injections once weekly for 48 weeks of double-blind treatment.
DRUGTocilizumab
Participants will receive 162 mg SC tocilizumab once weekly for 48 weeks of double-blind treatment. The same regimen will be given to all eligible participants for 48 weeks of open-label treatment.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of SSc according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria, meeting criteria for active disease and with total disease duration of less than or equal to (\</=) 60 months * mRSS of 10-35 units, inclusive * Agreement to remain abstinent or use an effective contraceptive method among males and females with childbearing potential
Exclusion criteria
* Pregnant or lactating females * Major surgery within 8 weeks prior to screening * Scleroderma limited to the face or areas distal to the elbows or knees * Rheumatic autoimmune disease other than SSc * Immunization with a live or attenuated vaccine within 4 weeks prior to Baseline * Known hypersensitivity to human, humanized, or murine monoclonal antibodies * Moderately severe nervous system, renal, endocrine, pulmonary, cardiovascular, or gastrointestinal (GI) disease not related to SSc, including diverticulitis or ulcerative lower GI disorders, or myocardial infarction (MI) within 6 months prior to screening * Active or significant history of infection, including treatment with intravenous (IV) antibiotics within 4 weeks or oral antibiotics within 2 weeks prior to screening * Significant history of tuberculosis (TB) * Primary or secondary immunodeficiency * Malignant disease, with the exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix * History of drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period | From baseline to week 48 | The efficacy of TCZ vs placebo is evaluated in terms of in mean change in mRSS. Skin thickness will be assessed by palpation and rated using an mRSS that ranges from 0 (normal) to 3 (severe skin thickening) across 17 different body sites. The total score is the sum of the individual skin scores from all of these sites and ranges from 0 to 51 units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period | From Baseline to Week 48 | The proportion of participants with threshold improvements in mRSS at Week 48 relative to baseline. |
| Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period | Baseline to week 48 | FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded. |
| Change in Forced Vital Capacity (FVC) During Double-blind Period | From Baseline to Week 48 | FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded. |
| Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period | From Baseline to Week 48 | The Health Assessment Questionnaire Disability Index (HAQ-DI) consists of 20 questions referring to eight component sets consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored on a 4-point scale from 0 to 3: 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. Overall score was computed as the sum of component set scores and divided by the number of component sets answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. The total score indicates the patient's self-assessed level of disability. This outcome measure represents the change in mean score from baseline. A negative change from baseline indicates improvement. |
| Change in Patient Global Assessment Score During Double-blind Period | From Baseline to Week 48 | The Patient's Global Assessment represents the patient's overall assessment of current SSc status on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating has no effect at all (symptom free), and 100 on the extreme right end indicating worst possible effect. |
| Change in Physician Global Assessment Score During Double-blind Period | From Baseline to Week 48 | The Physician's Global Assessment is to be completed on the basis of examination and overall assessment of the patient. The physician's assessment of the patient's SSc status will be scored on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating has no effect at all (symptom free), and 100 on the extreme right end indicating worst possible effect. |
| Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period | From Baseline to Week 48 | Time to treatment failure is defined as the time from randomization to the time of death, decline in percent-predicted FVC \> 10% relative to baseline, \> 20% increase in mRSS and an increase in mRSS of equal to or more than 5 points, or occurrence of a predefined SSc-related complication as adjudicated by the Clinical Adjudication Committee (whichever occurs first) during the 48-week double-blind treatment period. The median TTF was not estimable and is not presented for either treatment arm because of the low number of patients with events at Week 48. |
| Summary of Adverse Events During Double-blind Period | From Baseline until Week 48 | Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 20.1. NMSC = Non-Melanoma Skin Cancer |
| Incidence and Severity of Adverse Events During Double-blind Period | From Baseline until Week 48 | Adverse events listed according to MedDRA version 20.1 preferred terms and severity grade. |
| Number of Participants With Adverse Events Leading to Death During Double-blind Period | From Baseline up to Week 48 | Reason of death is coded using MedDRA 20.1 |
| Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | From Baseline up to Week 48 | Adverse event terms coded using MedDRA 20.1. Includes only those serious events adjudicated as SSC-related complications by an independent external committee. |
| Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | From Baseline up to Week 48 | A laboratory event occurred if the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade for a post-baseline laboratory measurement increased from baseline. |
| Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | From Baseline to Week 48 | A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator. |
| Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline | Baseline | Incidence of anti-Tocilizumab at baseline |
| Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | From Baseline to Week 48 | Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug. |
| Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Double-blind period (up to Week 48) | Incidence of anti-Tocilizumab antibodies during the study relative to the prevalence of anti-Tocilizumab antibodies at baseline. Samples that are positive for anti-TCZ in the screening assay will be further analyzed by a confirmation assay to confirm specificity. If the confirmation assay is positive, two additional tests will be performed: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype. |
| Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab | Baseline; during Weeks 8, 16, 24, 36, 48, 96, and/or at treatment discontinuation (up to 96 weeks); and 8 weeks after treatment discontinuation (up to 104 weeks overall) | Pre-specified analysis of the relationship between Anti-Tocilizumab Antibody status and safety, efficacy, and PK endpoints were not analyzed via subgroup analyses as there was only 1 patient with ADA-positive status. |
| Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | From Predose up to Week 48 | Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | From Baseline to Week 48 | Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | From Baseline to Week 48 | Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | From Baseline to Week 48 | Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | From Baseline to Week 48 | Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | From Baseline to Week 48 | Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | From Baseline to Week 48 | Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | From Baseline to Week 48 | Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | From Baseline to Week 48 | Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | From Baseline up to Week 48 | Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | From Baseline up to Week 48 | Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | From Baseline to Week 48 | Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter |
| Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | From Baseline to Week 48 | Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter |
| Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | From Baseline to Week 48 | In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml. |
| Summary of Adverse Events Up to Week 96 | Up to Week 96 | Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 21.1. NMSC = Non-Melanoma Skin Cancer |
| Number of Participants With Adverse Events Leading to Death Up to Week 96 | Up to Week 96 | — |
| Incidence and Severity of Adverse Events Up to Week 96 | Up to Week 96 | Adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) severity grade: 1 = mild, 2 = moderate, 3 = severe and/or requiring medical intervention but not life-threatening, 4 = life-threatening consequences, and 5 = death. |
| Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Up to Week 96 | Serum Soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug. |
| Percentage of Participants With Change in Digital Ulcer Count at Week 96 | From Baseline to Week 96 | A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator. |
| Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96 | Open-label period from Week 48 to 96 | Reported were the percentage of participants with post-baseline treatment-induced anti-TCZ antibodies. Positive samples underwent additional analyses: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype. |
| Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Up to Week 96 | Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Up to Week 96 | Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | From Baseline up to Week 96 | Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug. |
| Serum Tocilizumab Concentration, Mean, Up to Week 96 | Up to Week 96 | Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter |
Countries
Argentina, Belgium, Bulgaria, Canada, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Lithuania, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Romania, Spain, Switzerland, United Kingdom, United States
Participant flow
Pre-assignment details
Overall 212 participants were randomized on to the study, 107 to the placebo arm and 105 to the tocilizumab arm. One participant in placebo arm withdrew consent prior to receiving any treatment and one participant in the tocilizumab arm was withdrawn due to randomization error prior to receiving any treatment.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Placebo, Then Tocilizumab Open Label Participants received double-blind matching placebo from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96. | 106 |
| Double-Blind Tocilizumab, Then Tocilizumab Open Label Participants received double-blind tocilizumab from Baseline to Week 48. Participants then received open-label tocilizumab from Weeks 48 to 96. | 104 |
| Total | 210 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double Blind Period | Adverse Event | 3 | 2 |
| Double Blind Period | Death | 1 | 1 |
| Double Blind Period | Other | 0 | 1 |
| Double Blind Period | Withdrawal by Subject | 9 | 5 |
| Open Label Period | Adverse Event | 1 | 3 |
| Open Label Period | Death | 0 | 1 |
| Open Label Period | Lost to Follow-up | 1 | 0 |
| Open Label Period | Other | 0 | 2 |
| Open Label Period | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Double-Blind Tocilizumab, Then Tocilizumab Open Label | Total | Double-Blind Placebo, Then Tocilizumab Open Label |
|---|---|---|---|
| Age, Continuous | 47.0 Years STANDARD_DEVIATION 12.2 | 48.2 Years STANDARD_DEVIATION 12.4 | 49.3 Years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 39 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 168 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 25 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 85 Participants | 175 Participants | 90 Participants |
| Sex: Female, Male Female | 81 Participants | 171 Participants | 90 Participants |
| Sex: Female, Male Male | 23 Participants | 39 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 106 | 1 / 104 | 1 / 89 | 1 / 92 |
| other Total, other adverse events | 59 / 106 | 60 / 104 | 46 / 89 | 28 / 92 |
| serious Total, serious adverse events | 18 / 106 | 13 / 104 | 7 / 89 | 10 / 92 |
Outcome results
Primary
Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period
The efficacy of TCZ vs placebo is evaluated in terms of in mean change in mRSS. Skin thickness will be assessed by palpation and rated using an mRSS that ranges from 0 (normal) to 3 (severe skin thickening) across 17 different body sites. The total score is the sum of the individual skin scores from all of these sites and ranges from 0 to 51 units.
Time frame: From baseline to week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-Blind Placebo | Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period | -4.41 Units on a scale |
| Double-Blind Tocilizumab | Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period | -6.14 Units on a scale |
Comparison: Difference in least square means between the TCZ group and the Placebo group at week 48. Null hypothesis: There is no difference between the TCZ group and the placebo group in mean change in mRSS from baseline to Week 48.p-value: 0.098395% CI: [-3.78, 0.32]Repeated Measure
Secondary
Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period
FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded.
Time frame: Baseline to week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-Blind Placebo | Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period | -3.910 Percent Predicted FVC |
| Double-Blind Tocilizumab | Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period | -0.600 Percent Predicted FVC |
p-value: 0.0015Van Elteren
Secondary
Change in Forced Vital Capacity (FVC) During Double-blind Period
FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-Blind Placebo | Change in Forced Vital Capacity (FVC) During Double-blind Period | -0.19 Liters of air |
| Double-Blind Tocilizumab | Change in Forced Vital Capacity (FVC) During Double-blind Period | -0.02 Liters of air |
p-value: 0.000195% CI: [0.083, 0.25]Repeated Measure
Secondary
Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period
The Health Assessment Questionnaire Disability Index (HAQ-DI) consists of 20 questions referring to eight component sets consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored on a 4-point scale from 0 to 3: 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. Overall score was computed as the sum of component set scores and divided by the number of component sets answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. The total score indicates the patient's self-assessed level of disability. This outcome measure represents the change in mean score from baseline. A negative change from baseline indicates improvement.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-Blind Placebo | Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period | -0.06 Scores on a Scale |
| Double-Blind Tocilizumab | Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period | -0.11 Scores on a Scale |
p-value: 0.448995% CI: [-0.192, 0.085]Repeated Measure
Secondary
Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | -5.3 Units on a scale | Standard Deviation 7.77 |
| Double-Blind Placebo | Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -5.3 Units on a scale | Standard Deviation 7.77 |
| Double-Blind Placebo | Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | -5.3 Units on a scale | Standard Deviation 7.77 |
| Double-Blind Tocilizumab | Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | -8.0 Units on a scale | Standard Deviation 5.85 |
| Double-Blind Tocilizumab | Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -7.5 Units on a scale | Standard Deviation 5.06 |
| Double-Blind Tocilizumab | Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | -7.0 Units on a scale | Standard Deviation 6.26 |
Secondary
Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | -4.264 Percent | Standard Deviation 8.155 |
| Double-Blind Placebo | Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -4.264 Percent | Standard Deviation 8.155 |
| Double-Blind Placebo | Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | -4.264 Percent | Standard Deviation 8.155 |
| Double-Blind Tocilizumab | Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | 0.144 Percent | Standard Deviation 6.474 |
| Double-Blind Tocilizumab | Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -0.161 Percent | Standard Deviation 6.44 |
| Double-Blind Tocilizumab | Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | -0.297 Percent | Standard Deviation 7.895 |
Secondary
Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | -5.5 Units on a scale |
| Double-Blind Placebo | Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -5.5 Units on a scale |
| Double-Blind Placebo | Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | -5.5 Units on a scale |
| Double-Blind Tocilizumab | Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | -8.0 Units on a scale |
| Double-Blind Tocilizumab | Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -7.0 Units on a scale |
| Double-Blind Tocilizumab | Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | -6.0 Units on a scale |
Secondary
Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | -3.910 Percent |
| Double-Blind Placebo | Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -3.910 Percent |
| Double-Blind Placebo | Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | -3.910 Percent |
| Double-Blind Tocilizumab | Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Low Exposure | 0.525 Percent |
| Double-Blind Tocilizumab | Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | Medium Exposure | -1.600 Percent |
| Double-Blind Tocilizumab | Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48 | High Exposure | 0.000 Percent |
Secondary
Change in Patient Global Assessment Score During Double-blind Period
The Patient's Global Assessment represents the patient's overall assessment of current SSc status on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating has no effect at all (symptom free), and 100 on the extreme right end indicating worst possible effect.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-Blind Placebo | Change in Patient Global Assessment Score During Double-blind Period | -7.66 mm |
| Double-Blind Tocilizumab | Change in Patient Global Assessment Score During Double-blind Period | -10.10 mm |
p-value: 0.433995% CI: [-8.57, 3.7]Repeated Measure
Secondary
Change in Physician Global Assessment Score During Double-blind Period
The Physician's Global Assessment is to be completed on the basis of examination and overall assessment of the patient. The physician's assessment of the patient's SSc status will be scored on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating has no effect at all (symptom free), and 100 on the extreme right end indicating worst possible effect.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-Blind Placebo | Change in Physician Global Assessment Score During Double-blind Period | -19.99 mm |
| Double-Blind Tocilizumab | Change in Physician Global Assessment Score During Double-blind Period | -22.45 mm |
p-value: 0.437895% CI: [-8.72, 3.79]Repeated Measure
Secondary
Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab
Pre-specified analysis of the relationship between Anti-Tocilizumab Antibody status and safety, efficacy, and PK endpoints were not analyzed via subgroup analyses as there was only 1 patient with ADA-positive status.
Time frame: Baseline; during Weeks 8, 16, 24, 36, 48, 96, and/or at treatment discontinuation (up to 96 weeks); and 8 weeks after treatment discontinuation (up to 104 weeks overall)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-Blind Placebo | Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab | NA Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab | NA Units on a scale |
Secondary
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 20.4 Units on a scale | Standard Deviation 6.95 |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 18.6 Units on a scale | Standard Deviation 7.78 |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 17.9 Units on a scale | Standard Deviation 8.71 |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 16.9 Units on a scale | Standard Deviation 9.38 |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 16.2 Units on a scale | Standard Deviation 10.24 |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 14.8 Units on a scale | Standard Deviation 9.89 |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 13.7 Units on a scale | Standard Deviation 7.07 |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 19.8 Units on a scale | Standard Deviation 6.82 |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 15.6 Units on a scale | Standard Deviation 7.5 |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 17.9 Units on a scale | Standard Deviation 7.35 |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 12.8 Units on a scale | Standard Deviation 7.2 |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 16.7 Units on a scale | Standard Deviation 7.31 |
Secondary
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 19.0 Units on a scale |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 18.0 Units on a scale |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 17.0 Units on a scale |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 16.0 Units on a scale |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 14.0 Units on a scale |
| Double-Blind Placebo | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 14.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 11.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 19.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 15.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 17.5 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 11.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 15.0 Units on a scale |
Secondary
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 20.4 Units on a scale | Standard Deviation 6.95 |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 18.6 Units on a scale | Standard Deviation 7.78 |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 17.9 Units on a scale | Standard Deviation 8.71 |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 16.9 Units on a scale | Standard Deviation 9.38 |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 16.2 Units on a scale | Standard Deviation 10.24 |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 14.8 Units on a scale | Standard Deviation 9.89 |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 13.2 Units on a scale | Standard Deviation 4.97 |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 20.3 Units on a scale | Standard Deviation 5.56 |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 14.7 Units on a scale | Standard Deviation 5.61 |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 17.9 Units on a scale | Standard Deviation 5.84 |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 12.2 Units on a scale | Standard Deviation 6.03 |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 16.2 Units on a scale | Standard Deviation 5.58 |
Secondary
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 19.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 18.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 17.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 16.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 14.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 14.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 13.5 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 20.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 14.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 16.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 12.5 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 15.0 Units on a scale |
Secondary
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 20.4 Units on a scale | Standard Deviation 6.95 |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 18.6 Units on a scale | Standard Deviation 7.78 |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 17.9 Units on a scale | Standard Deviation 8.71 |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 16.9 Units on a scale | Standard Deviation 9.38 |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 16.2 Units on a scale | Standard Deviation 10.24 |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 14.8 Units on a scale | Standard Deviation 9.89 |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 13.4 Units on a scale | Standard Deviation 6.2 |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 19.1 Units on a scale | Standard Deviation 6.24 |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 14.6 Units on a scale | Standard Deviation 6.66 |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 17.2 Units on a scale | Standard Deviation 6.17 |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 11.6 Units on a scale | Standard Deviation 5.72 |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 16.2 Units on a scale | Standard Deviation 6.1 |
Secondary
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-\<41 ug/ml, Medium = 41-\<=61.1 ug/ml, High = 61.1-\<=145 ug/ml.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 19.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 18.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 17.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 16.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 14.0 Units on a scale |
| Double-Blind Placebo | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 14.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 36 | 13.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Baseline | 18.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 24 | 14.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 8 | 17.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 48 | 11.0 Units on a scale |
| Double-Blind Tocilizumab | Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48 | Week 16 | 16.0 Units on a scale |
Secondary
Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48
Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Predose up to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Baseline | 34.72 mm/hr | Standard Deviation 18.49 |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Week 4 | 31.38 mm/hr | Standard Deviation 19 |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Week 24 | 28.49 mm/hr | Standard Deviation 20.86 |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Week 48 | 26.59 mm/hr | Standard Deviation 18.62 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Week 48 | 10.82 mm/hr | Standard Deviation 15.53 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Baseline | 34.83 mm/hr | Standard Deviation 16.29 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Week 24 | 8.46 mm/hr | Standard Deviation 8.63 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48 | Week 4 | 14.29 mm/hr | Standard Deviation 12.98 |
Secondary
Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48
Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Baseline | 33.0 mm/hr |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Week 4 | 30.00 mm/hr |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Week 24 | 25.00 mm/hr |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Week 48 | 22.50 mm/hr |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Week 48 | 5.50 mm/hr |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Baseline | 33.50 mm/hr |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Week 24 | 5.00 mm/hr |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48 | Week 4 | 9.50 mm/hr |
Secondary
Erythrocyte Sedimentation Rate (ESR) Up to Week 96
Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: Up to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Baseline | 34.72 mm/hr | Standard Deviation 18.49 |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 4 | 31.38 mm/hr | Standard Deviation 19 |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 24 | 28.49 mm/hr | Standard Deviation 20.86 |
| Double-Blind Placebo | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 48 | 26.23 mm/hr | Standard Deviation 18.53 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 24 | 8.46 mm/hr | Standard Deviation 8.63 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Baseline | 34.83 mm/hr | Standard Deviation 16.29 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 4 | 14.29 mm/hr | Standard Deviation 12.98 |
| Double-Blind Tocilizumab | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 48 | 10.89 mm/hr | Standard Deviation 15.39 |
| Placebo, Then Tocilizumab Open Label | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 72 | 9.54 mm/hr | Standard Deviation 9.47 |
| Placebo, Then Tocilizumab Open Label | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 96 | 9.67 mm/hr | Standard Deviation 8.67 |
| Tocilizumab, Then Tocilizumab Open Label | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 72 | 8.29 mm/hr | Standard Deviation 10.13 |
| Tocilizumab, Then Tocilizumab Open Label | Erythrocyte Sedimentation Rate (ESR) Up to Week 96 | Week 96 | 8.06 mm/hr | Standard Deviation 8.86 |
Secondary
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
Adverse event terms coded using MedDRA 20.1. Includes only those serious events adjudicated as SSC-related complications by an independent external committee.
Time frame: From Baseline up to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | INFECTED SKIN ULCER | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | PAIN | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | CARDIAC FAILURE CHRONIC | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | WEIGHT DECREASED | 0 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | OSTEOMYELITIS | 0 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | SCLERODERMA | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | MYOCARDITIS | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | HYPOKINESIA | 0 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | WOUND INFECTION | 0 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | ADJUSTMENT DISORDER | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | MICROVASCULAR CORONARY ARTERY DISEASE | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | SCLERODERMA RENAL CRISIS | 0 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | ILEUS PARALYTIC | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | DIGITAL PITTING SCAR | 1 Number of Participants |
| Double-Blind Placebo | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | CARDIAC FAILURE | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | DIGITAL PITTING SCAR | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | CARDIAC FAILURE | 1 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | CARDIAC FAILURE CHRONIC | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | MICROVASCULAR CORONARY ARTERY DISEASE | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | MYOCARDITIS | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | INFECTED SKIN ULCER | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | OSTEOMYELITIS | 1 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | WOUND INFECTION | 1 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | ILEUS PARALYTIC | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | PAIN | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | WEIGHT DECREASED | 1 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | SCLERODERMA | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | HYPOKINESIA | 1 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | ADJUSTMENT DISORDER | 0 Number of Participants |
| Double-Blind Tocilizumab | Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period | SCLERODERMA RENAL CRISIS | 1 Number of Participants |
Secondary
Incidence and Severity of Adverse Events During Double-blind Period
Adverse events listed according to MedDRA version 20.1 preferred terms and severity grade.
Time frame: From Baseline until Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LIGAMENT SPRAIN GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CONSTIPATION GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPEPSIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTRIC DISORDER GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTRIC POLYPS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE INDURATION GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE PRURITUS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAINFUL RESPIRATION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PLEURAL EFFUSION GRADE 4 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ARTHROPOD STING GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY ANAEMIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NEUTROPENIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NEUTROPENIA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ACUTE MYOCARDIAL INFARCTION GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GLAUCOMA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GLAUCOMA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NASOPHARYNGITIS GRADE 1 | 6 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NASOPHARYNGITIS GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | URINARY TRACT INFECTION GRADE 1 | 5 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | URINARY TRACT INFECTION GRADE 2 | 5 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | URINARY TRACT INFECTION GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROENTERITIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROENTERITIS GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HERPES ZOSTER GRADE 2 | 5 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HERPES ZOSTER GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PHARYNGITIS GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PHARYNGITIS GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INFECTED SKIN ULCER GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INFECTED SKIN ULCER GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INFECTED SKIN ULCER GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BRONCHITIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BRONCHITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INFLUENZA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INFLUENZA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LATENT TUBERCULOSIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LATENT TUBERCULOSIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMONIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMONIA GRADE 3 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SINUSITIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SINUSITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SINUSITIS GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CYSTITIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CYSTITIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LOCALISED INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LOCALISED INFECTION GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ORAL CANDIDIASIS GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PARONYCHIA GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PARONYCHIA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VULVOVAGINAL MYCOTIC INFECTION GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CANDIDA INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CANDIDA INFECTION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FOLLICULITIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FOLLICULITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROINTESTINAL INFECTION GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HORDEOLUM GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RHINITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SOFT TISSUE INFECTION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SOFT TISSUE INFECTION GRADE 4 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TINEA PEDIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TINEA PEDIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VIRAL UPPER RESPIRATORY TRACT INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VIRAL UPPER RESPIRATORY TRACT INFECTION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABSCESS JAW GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ACUTE SINUSITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BACTERAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BODY TINEA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CAMPYLOBACTER GASTROENTERITIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROENTERITIS VIRAL GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROINTESTINAL BACTERIAL OVERGROWTH GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROINTESTINAL VIRAL INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GINGIVITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HERPES SIMPLEX GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INFECTIOUS MONONUCLEOSIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LARYNGITIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LICE INFESTATION GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OESOPHAGEAL CANDIDIASIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ORAL HERPES GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOMYELITIS GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PELVIC INFLAMMATORY DISEASE GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERIODONTITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERIORBITAL CELLULITIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PHARYNGITIS STREPTOCOCCAL GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PULMONARY TUBERCULOSIS GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PULPITIS DENTAL GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PYELONEPHRITIS CHRONIC GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RASH PUSTULAR GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION BACTERIAL GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SEPSIS GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN BACTERIAL INFECTION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TONSILLITIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TOOTH INFECTION GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VIRAL INFECTION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION STAPHYLOCOCCAL GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MYOSITIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRALGIA GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRALGIA GRADE 2 | 8 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRALGIA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BACK PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BACK PAIN GRADE 2 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE SPASMS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE SPASMS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE SPASMS GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN EXTREMITY GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN EXTREMITY GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN EXTREMITY GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULOSKELETAL PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULOSKELETAL PAIN GRADE 2 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BURSITIS GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BURSITIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MYALGIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MYALGIA GRADE 2 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRITIS GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INTERVERTEBRAL DISC PROTRUSION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INTERVERTEBRAL DISC PROTRUSION GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MYOSITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOCHONDROSIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FOOT DEFORMITY GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SCLERODERMA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SCLERODERMA GRADE 4 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SJOGREN'S SYNDROME GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SJOGREN'S SYNDROME GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SPINAL OSTEOARTHRITIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SPINAL OSTEOARTHRITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EXTREMITY CONTRACTURE GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FIBROMYALGIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FLANK PAIN GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | JOINT STIFFNESS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | JOINT SWELLING GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE CONTRACTURE GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE FATIGUE GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULAR WEAKNESS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULOSKELETAL CHEST PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MYOPATHY GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NECK PAIN GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOPENIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOPOROSIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOPOROTIC FRACTURE GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN JAW GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | POLYARTHRITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TENOSYNOVITIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TENOSYNOVITIS STENOSANS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ULCER GRADE 1 | 5 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ULCER GRADE 2 | 7 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ULCER GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PRURITUS GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PRURITUS GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RASH GRADE 1 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RASH GRADE 2 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ERYTHEMA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ECZEMA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ECZEMA GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ROSACEA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ROSACEA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN TIGHTNESS GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DERMATITIS CONTACT GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INGROWING NAIL GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INGROWING NAIL GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MACULE GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NIGHT SWEATS GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN DISCOLOURATION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN FISSURES GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN HYPERTROPHY GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN INDURATION GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | URTICARIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | URTICARIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ALOPECIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLISTER GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CHLOASMA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | COLD SWEAT GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DECUBITUS ULCER GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DERMATITIS ACNEIFORM GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DERMATITIS ATOPIC GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIGITAL PITTING SCAR GRADE 4 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DRY SKIN GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ECCHYMOSIS GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EXCESSIVE GRANULATION TISSUE GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERTRICHOSIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ONYCHOLYSIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN OF SKIN GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAPULE GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RASH ERYTHEMATOUS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RASH MACULO-PAPULAR GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN DEPIGMENTATION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN FIBROSIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN HYPOPIGMENTATION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN OEDEMA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VITILIGO GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIARRHOEA GRADE 1 | 5 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIARRHOEA GRADE 2 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROOESOPHAGEAL REFLUX DISEASE GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTROOESOPHAGEAL REFLUX DISEASE GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NAUSEA GRADE 1 | 5 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NAUSEA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CONSTIPATION GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPEPSIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPHAGIA GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPHAGIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | STOMATITIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | STOMATITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VOMITING GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VOMITING GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISCOMFORT GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISCOMFORT GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISTENSION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISTENSION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN UPPER GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DENTAL CARIES GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FAECES SOFT GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HAEMORRHOIDS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HAEMORRHOIDS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TOOTHACHE GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANAL HAEMORRHAGE GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CHRONIC GASTRITIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIVERTICULUM INTESTINAL GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DRY MOUTH GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DUODENITIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GASTRITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HAEMATOCHEZIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ILEUS PARALYTIC GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LOOSE TOOTH GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OESOPHAGEAL DISORDER GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OESOPHAGEAL HYPOMOTILITY GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERIODONTAL DISEASE GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMATOSIS INTESTINALIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RANULA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SWOLLEN TONGUE GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FATIGUE GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FATIGUE GRADE 2 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OEDEMA PERIPHERAL GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OEDEMA PERIPHERAL GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ASTHENIA GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ASTHENIA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CALCINOSIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE ERYTHEMA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE ERYTHEMA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE ERYTHEMA GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE REACTION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE REACTION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PAIN GRADE 4 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CHEST PAIN GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CYST GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CYST GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INFLUENZA LIKE ILLNESS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DEATH GRADE 5 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FEELING HOT GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GRANULOMA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE EXTRAVASATION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NODULE GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MALAISE GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERIPHERAL SWELLING GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PYREXIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SENSATION OF FOREIGN BODY GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VESSEL PUNCTURE SITE PAIN GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT DECREASED GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT DECREASED GRADE 2 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ALANINE AMINOTRANSFERASE INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ALANINE AMINOTRANSFERASE INCREASED GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ALANINE AMINOTRANSFERASE INCREASED GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ASPARTATE AMINOTRANSFERASE INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ASPARTATE AMINOTRANSFERASE INCREASED GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ASPARTATE AMINOTRANSFERASE INCREASED GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC ENZYME INCREASED GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC ENZYME INCREASED GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC ENZYME INCREASED GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT INCREASED GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TRANSAMINASES INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TRANSAMINASES INCREASED GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CHOLESTEROL INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CHOLESTEROL INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | UPPER RESPIRATORY TRACT INFECTION GRADE 1 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | UPPER RESPIRATORY TRACT INFECTION GRADE 2 | 7 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | UPPER RESPIRATORY TRACT INFECTION GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CREATINE PHOSPHOKINASE INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CREATINE PHOSPHOKINASE INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD BILIRUBIN INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD URINE PRESENT GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CAROTID INTIMA-MEDIA THICKNESS INCREASED GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | COMPUTERISED TOMOGRAM THORAX ABNORMAL GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HAEMOGLOBIN DECREASED GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LIVER FUNCTION TEST ABNORMAL GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LOW DENSITY LIPOPROTEIN INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PROTEIN URINE PRESENT GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TRANSFERRIN SATURATION INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TUBERCULIN TEST POSITIVE GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | URINE BILIRUBIN INCREASED GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | UROBILINOGEN URINE INCREASED GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WHITE BLOOD CELLS URINE POSITIVE GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | COUGH GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | COUGH GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INTERSTITIAL LUNG DISEASE GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INTERSTITIAL LUNG DISEASE GRADE 2 | 5 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EPISTAXIS GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EPISTAXIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA EXERTIONAL GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA EXERTIONAL GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA EXERTIONAL GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OROPHARYNGEAL PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OROPHARYNGEAL PAIN GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PRODUCTIVE COUGH GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSPHONIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HAEMOPTYSIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMONITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RHINITIS ALLERGIC GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RHINORRHOEA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HEADACHE GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HEADACHE GRADE 2 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIZZINESS GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIZZINESS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NEUROPATHY PERIPHERAL GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | POST HERPETIC NEURALGIA GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CARPAL TUNNEL SYNDROME GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSGEUSIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPOAESTHESIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPOKINESIA GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MEMORY IMPAIRMENT GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NERVE COMPRESSION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NEURALGIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PARAESTHESIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PARKINSONISM GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PRESYNCOPE GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RADICULAR PAIN GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SENSORY LOSS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SOMNOLENCE GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LIMB INJURY GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LIMB INJURY GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LIMB INJURY GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FALL GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FALL GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EAR INJURY GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LACERATION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LACERATION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SCAR GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SCAR GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WOUND GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WOUND GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANIMAL BITE GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANKLE FRACTURE GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CONTUSION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CRANIOCEREBRAL INJURY GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EXCORIATION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FACE INJURY GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INJURY CORNEAL GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | JOINT INJURY GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LIMB TRAUMATIC AMPUTATION GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MENISCUS INJURY GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE RUPTURE GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE STRAIN GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ROAD TRAFFIC ACCIDENT GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ABRASION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SPINAL COMPRESSION FRACTURE GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | THERMAL BURN GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA GRADE 1 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA GRADE 2 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY ANAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY ANAEMIA GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LYMPHOPENIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LYMPHOPENIA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA MEGALOBLASTIC GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EOSINOPHILIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LEUKOCYTOSIS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LEUKOPENIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LYMPHADENOPATHY MEDIASTINAL GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MICROANGIOPATHIC HAEMOLYTIC ANAEMIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MICROCYTIC ANAEMIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | THROMBOCYTOPENIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DECREASED APPETITE GRADE 1 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSLIPIDAEMIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSLIPIDAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERCHOLESTEROLAEMIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERCHOLESTEROLAEMIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERTRIGLYCERIDAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIABETES MELLITUS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIABETIC KETOACIDOSIS GRADE 4 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DIABETIC METABOLIC DECOMPENSATION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FOLATE DEFICIENCY GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GOUT GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERGLYCAEMIA GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERLIPIDAEMIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPONATRAEMIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OBESITY GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT FLUCTUATION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PALPITATIONS GRADE 1 | 4 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PALPITATIONS GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BUNDLE BRANCH BLOCK RIGHT GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BUNDLE BRANCH BLOCK RIGHT GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERICARDIAL EFFUSION GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERICARDIAL EFFUSION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANGINA PECTORIS GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ATRIAL FIBRILLATION GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ATRIAL TACHYCARDIA GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BRADYCARDIA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CARDIAC FAILURE GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CARDIAC FAILURE CHRONIC GRADE 5 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MICROVASCULAR CORONARY ARTERY DISEASE GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MYOCARDIAL INFARCTION GRADE 5 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MYOCARDITIS GRADE 5 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERICARDITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SUPRAVENTRICULAR EXTRASYSTOLES GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TACHYCARDIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANXIETY GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ANXIETY GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | INSOMNIA GRADE 1 | 2 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | STRESS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ADJUSTMENT DISORDER GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DEPRESSED MOOD GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DEPRESSION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GENERALISED ANXIETY DISORDER GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SLEEP DISORDER GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CHALAZION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLEPHARITIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CATARACT GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CONJUNCTIVAL HAEMORRHAGE GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DRY EYE GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | EYELID OEDEMA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | KERATITIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VISUAL IMPAIRMENT GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RAYNAUD'S PHENOMENON GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RAYNAUD'S PHENOMENON GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD PRESSURE FLUCTUATION GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERTENSION GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPOTENSION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PERIPHERAL ISCHAEMIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | THROMBOPHLEBITIS GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VASCULITIS GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ACUTE KIDNEY INJURY GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | DYSURIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HAEMATURIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NEPHROLITHIASIS GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RENAL COLIC GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RENAL CYST GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | RENAL PAIN GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SCLERODERMA RENAL CRISIS GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | AMENORRHOEA GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BREAST CYST GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CERVICAL POLYP GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | ERECTILE DYSFUNCTION GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | GENITAL RASH GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MENSTRUATION IRREGULAR GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | OVARIAN CYST RUPTURED GRADE 2 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PENILE PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | B-CELL LYMPHOMA GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BENIGN BONE NEOPLASM GRADE 3 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BENIGN LUNG NEOPLASM GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | BREAST CANCER GRADE 3 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | LUNG ADENOCARCINOMA GRADE 4 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | SKIN PAPILLOMA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | FOOD ALLERGY GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPERSENSITIVITY GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | TYPE I HYPERSENSITIVITY GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MICROSTOMIA GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | MICROSTOMIA GRADE 2 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | PRESBYACUSIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | VERTIGO GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HYPOTHYROIDISM GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | THYROID MASS GRADE 1 | 1 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC STEATOSIS GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | NEEDLE ISSUE GRADE 1 | 0 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events During Double-blind Period | CATARACT OPERATION GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LIMB TRAUMATIC AMPUTATION GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OEDEMA PERIPHERAL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CONSTIPATION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RENAL CYST GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DUODENITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ASTHENIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTRIC DISORDER GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MENISCUS INJURY GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTRIC POLYPS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ASTHENIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE INDURATION GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INSOMNIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE PRURITUS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CALCINOSIS GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAINFUL RESPIRATION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE RUPTURE GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PLEURAL EFFUSION GRADE 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE ERYTHEMA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ARTHROPOD STING GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | THYROID MASS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE ERYTHEMA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE STRAIN GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NEUTROPENIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE ERYTHEMA GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERICARDIAL EFFUSION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | STRESS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE REACTION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GLAUCOMA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ROAD TRAFFIC ACCIDENT GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE REACTION GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NASOPHARYNGITIS GRADE 1 | 10 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RENAL PAIN GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NASOPHARYNGITIS GRADE 2 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | URINARY TRACT INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ABRASION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | URINARY TRACT INFECTION GRADE 2 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | URINARY TRACT INFECTION GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ADJUSTMENT DISORDER GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROENTERITIS GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN GRADE 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROENTERITIS GRADE 2 | 4 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SPINAL COMPRESSION FRACTURE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HERPES ZOSTER GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CHEST PAIN GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HERPES ZOSTER GRADE 3 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LUNG ADENOCARCINOMA GRADE 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PHARYNGITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CYST GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PHARYNGITIS GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | THERMAL BURN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INFECTED SKIN ULCER GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CYST GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INFECTED SKIN ULCER GRADE 2 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DEPRESSED MOOD GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INFECTED SKIN ULCER GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INFLUENZA LIKE ILLNESS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BRONCHITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BRONCHITIS GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DEATH GRADE 5 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INFLUENZA GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SCLERODERMA RENAL CRISIS GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INFLUENZA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MALAISE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LATENT TUBERCULOSIS GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FEELING HOT GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LATENT TUBERCULOSIS GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMONIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GRANULOMA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMONIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY ANAEMIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DEPRESSION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJECTION SITE EXTRAVASATION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY ANAEMIA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SINUSITIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NODULE GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SINUSITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PRESBYACUSIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SINUSITIS GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERIPHERAL SWELLING GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY ANAEMIA GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PYREXIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GENERALISED ANXIETY DISORDER GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CYSTITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SENSATION OF FOREIGN BODY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CYSTITIS GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LYMPHOPENIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LOCALISED INFECTION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VESSEL PUNCTURE SITE PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LOCALISED INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | AMENORRHOEA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ORAL CANDIDIASIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT DECREASED GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PARONYCHIA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LYMPHOPENIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PARONYCHIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT DECREASED GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VULVOVAGINAL MYCOTIC INFECTION GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NEUTROPENIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CANDIDA INFECTION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ALANINE AMINOTRANSFERASE INCREASED GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CANDIDA INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SLEEP DISORDER GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FOLLICULITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ALANINE AMINOTRANSFERASE INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FOLLICULITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANAEMIA MEGALOBLASTIC GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROINTESTINAL INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ALANINE AMINOTRANSFERASE INCREASED GRADE 3 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HORDEOLUM GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN PAPILLOMA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RHINITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ASPARTATE AMINOTRANSFERASE INCREASED GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SOFT TISSUE INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EOSINOPHILIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SOFT TISSUE INFECTION GRADE 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ASPARTATE AMINOTRANSFERASE INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TINEA PEDIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CHALAZION GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TINEA PEDIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ASPARTATE AMINOTRANSFERASE INCREASED GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VIRAL UPPER RESPIRATORY TRACT INFECTION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LEUKOCYTOSIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VIRAL UPPER RESPIRATORY TRACT INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC ENZYME INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABSCESS JAW GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GLAUCOMA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ACUTE SINUSITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC ENZYME INCREASED GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BACTERAEMIA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LEUKOPENIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BODY TINEA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC ENZYME INCREASED GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CAMPYLOBACTER GASTROENTERITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BREAST CYST GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROENTERITIS VIRAL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT INCREASED GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROINTESTINAL BACTERIAL OVERGROWTH GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LYMPHADENOPATHY MEDIASTINAL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROINTESTINAL VIRAL INFECTION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TRANSAMINASES INCREASED GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GINGIVITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLEPHARITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HERPES SIMPLEX GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TRANSAMINASES INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INFECTIOUS MONONUCLEOSIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MICROANGIOPATHIC HAEMOLYTIC ANAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LARYNGITIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CHOLESTEROL INCREASED GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LICE INFESTATION GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NEEDLE ISSUE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OESOPHAGEAL CANDIDIASIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CHOLESTEROL INCREASED GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ORAL HERPES GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MICROCYTIC ANAEMIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOMYELITIS GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | UPPER RESPIRATORY TRACT INFECTION GRADE 1 | 7 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PELVIC INFLAMMATORY DISEASE GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CATARACT GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERIODONTITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | UPPER RESPIRATORY TRACT INFECTION GRADE 2 | 4 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERIORBITAL CELLULITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | THROMBOCYTOPENIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PHARYNGITIS STREPTOCOCCAL GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | UPPER RESPIRATORY TRACT INFECTION GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PULMONARY TUBERCULOSIS GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CERVICAL POLYP GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PULPITIS DENTAL GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CREATINE PHOSPHOKINASE INCREASED GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PYELONEPHRITIS CHRONIC GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DECREASED APPETITE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RASH PUSTULAR GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD CREATINE PHOSPHOKINASE INCREASED GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RESPIRATORY TRACT INFECTION BACTERIAL GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CONJUNCTIVAL HAEMORRHAGE GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SEPSIS GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD BILIRUBIN INCREASED GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN BACTERIAL INFECTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSLIPIDAEMIA GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TONSILLITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD URINE PRESENT GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TOOTH INFECTION GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FOOD ALLERGY GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VIRAL INFECTION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CAROTID INTIMA-MEDIA THICKNESS INCREASED GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSLIPIDAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WOUND INFECTION STAPHYLOCOCCAL GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | COMPUTERISED TOMOGRAM THORAX ABNORMAL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRALGIA GRADE 1 | 8 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DRY EYE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRALGIA GRADE 2 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HAEMOGLOBIN DECREASED GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRALGIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERCHOLESTEROLAEMIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BACK PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LIVER FUNCTION TEST ABNORMAL GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BACK PAIN GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ERECTILE DYSFUNCTION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE SPASMS GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LOW DENSITY LIPOPROTEIN INCREASED GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE SPASMS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERCHOLESTEROLAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE SPASMS GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PROTEIN URINE PRESENT GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN EXTREMITY GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EYELID OEDEMA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN EXTREMITY GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TRANSFERRIN SATURATION INCREASED GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN EXTREMITY GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERTRIGLYCERIDAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULOSKELETAL PAIN GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TUBERCULIN TEST POSITIVE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULOSKELETAL PAIN GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VERTIGO GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BURSITIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | URINE BILIRUBIN INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BURSITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIABETES MELLITUS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MYALGIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | UROBILINOGEN URINE INCREASED GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MYALGIA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | KERATITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ARTHRITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WHITE BLOOD CELLS URINE POSITIVE GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INTERVERTEBRAL DISC PROTRUSION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIABETIC KETOACIDOSIS GRADE 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INTERVERTEBRAL DISC PROTRUSION GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MYOSITIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | COUGH GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MYOSITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GENITAL RASH GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOCHONDROSIS GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | COUGH GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FOOT DEFORMITY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIABETIC METABOLIC DECOMPENSATION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SCLERODERMA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INTERSTITIAL LUNG DISEASE GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SCLERODERMA GRADE 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VISUAL IMPAIRMENT GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SJOGREN'S SYNDROME GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INTERSTITIAL LUNG DISEASE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SJOGREN'S SYNDROME GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FOLATE DEFICIENCY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SPINAL OSTEOARTHRITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SPINAL OSTEOARTHRITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERSENSITIVITY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EXTREMITY CONTRACTURE GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FIBROMYALGIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GOUT GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FLANK PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EPISTAXIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | JOINT STIFFNESS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RAYNAUD'S PHENOMENON GRADE 1 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | JOINT SWELLING GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EPISTAXIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE CONTRACTURE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERGLYCAEMIA GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCLE FATIGUE GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA EXERTIONAL GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULAR WEAKNESS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MENSTRUATION IRREGULAR GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MUSCULOSKELETAL CHEST PAIN GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA EXERTIONAL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MYOPATHY GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERLIPIDAEMIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NECK PAIN GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPNOEA EXERTIONAL GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOPENIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RAYNAUD'S PHENOMENON GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOPOROSIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OROPHARYNGEAL PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OSTEOPOROTIC FRACTURE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPONATRAEMIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN IN JAW GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OROPHARYNGEAL PAIN GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | POLYARTHRITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HEPATIC STEATOSIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TENOSYNOVITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PRODUCTIVE COUGH GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TENOSYNOVITIS STENOSANS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | IRON DEFICIENCY GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ULCER GRADE 1 | 8 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPHONIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ULCER GRADE 2 | 5 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLOOD PRESSURE FLUCTUATION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN ULCER GRADE 3 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HAEMOPTYSIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PRURITUS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OBESITY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PRURITUS GRADE 2 | 5 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMONITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RASH GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OVARIAN CYST RUPTURED GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RASH GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RHINITIS ALLERGIC GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ERYTHEMA GRADE 1 | 4 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WEIGHT FLUCTUATION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ECZEMA GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RHINORRHOEA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ECZEMA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERTENSION GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ROSACEA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HEADACHE GRADE 1 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ROSACEA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PALPITATIONS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN TIGHTNESS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HEADACHE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DERMATITIS CONTACT GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TYPE I HYPERSENSITIVITY GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INGROWING NAIL GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIZZINESS GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INGROWING NAIL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PALPITATIONS GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MACULE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIZZINESS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NIGHT SWEATS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPOTENSION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN DISCOLOURATION GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NEUROPATHY PERIPHERAL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN FISSURES GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BUNDLE BRANCH BLOCK RIGHT GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN HYPERTROPHY GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | POST HERPETIC NEURALGIA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN INDURATION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PENILE PAIN GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | URTICARIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CARPAL TUNNEL SYNDROME GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | URTICARIA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BUNDLE BRANCH BLOCK RIGHT GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ALOPECIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSGEUSIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BLISTER GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERIPHERAL ISCHAEMIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CHLOASMA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPOAESTHESIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | COLD SWEAT GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERICARDIAL EFFUSION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DECUBITUS ULCER GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPOKINESIA GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DERMATITIS ACNEIFORM GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPOTHYROIDISM GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DERMATITIS ATOPIC GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MEMORY IMPAIRMENT GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIGITAL PITTING SCAR GRADE 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ACUTE MYOCARDIAL INFARCTION GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DRY SKIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NERVE COMPRESSION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ECCHYMOSIS GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | THROMBOPHLEBITIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EXCESSIVE GRANULATION TISSUE GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NEURALGIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HYPERTRICHOSIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANGINA PECTORIS GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ONYCHOLYSIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PARAESTHESIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAIN OF SKIN GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | B-CELL LYMPHOMA GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PAPULE GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PARKINSONISM GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RASH ERYTHEMATOUS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ATRIAL FIBRILLATION GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RASH MACULO-PAPULAR GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PRESYNCOPE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN DEPIGMENTATION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VASCULITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN FIBROSIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RADICULAR PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN HYPOPIGMENTATION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ATRIAL TACHYCARDIA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SKIN OEDEMA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SENSORY LOSS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VITILIGO GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MICROSTOMIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIARRHOEA GRADE 1 | 6 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SOMNOLENCE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIARRHOEA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BRADYCARDIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROOESOPHAGEAL REFLUX DISEASE GRADE 1 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LIMB INJURY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTROOESOPHAGEAL REFLUX DISEASE GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ACUTE KIDNEY INJURY GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NAUSEA GRADE 1 | 3 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LIMB INJURY GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NAUSEA GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CARDIAC FAILURE GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LIMB INJURY GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BENIGN BONE NEOPLASM GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FALL GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPEPSIA GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CARDIAC FAILURE CHRONIC GRADE 5 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPEPSIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FALL GRADE 2 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPHAGIA GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSURIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DYSPHAGIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EAR INJURY GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | STOMATITIS GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MICROVASCULAR CORONARY ARTERY DISEASE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | STOMATITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LACERATION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VOMITING GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CATARACT OPERATION GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | VOMITING GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LACERATION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISCOMFORT GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MYOCARDIAL INFARCTION GRADE 5 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISCOMFORT GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SCAR GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISTENSION GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HAEMATURIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL DISTENSION GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SCAR GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ABDOMINAL PAIN UPPER GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MYOCARDITIS GRADE 5 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DENTAL CARIES GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WOUND GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FAECES SOFT GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BENIGN LUNG NEOPLASM GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HAEMORRHOIDS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | WOUND GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HAEMORRHOIDS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERICARDITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TOOTHACHE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANIMAL BITE GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANAL HAEMORRHAGE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | NEPHROLITHIASIS GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CHRONIC GASTRITIS GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANKLE FRACTURE GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DIVERTICULUM INTESTINAL GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SUPRAVENTRICULAR EXTRASYSTOLES GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | DRY MOUTH GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CONTUSION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | MICROSTOMIA GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | GASTRITIS GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CRANIOCEREBRAL INJURY GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | HAEMATOCHEZIA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | TACHYCARDIA GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ILEUS PARALYTIC GRADE 3 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | EXCORIATION GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LOOSE TOOTH GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RENAL COLIC GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OESOPHAGEAL DISORDER GRADE 1 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FACE INJURY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OESOPHAGEAL HYPOMOTILITY GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANXIETY GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PERIODONTAL DISEASE GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | INJURY CORNEAL GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | PNEUMATOSIS INTESTINALIS GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | BREAST CANCER GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | RANULA GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | JOINT INJURY GRADE 3 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | SWOLLEN TONGUE GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | CONSTIPATION GRADE 1 | 2 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FATIGUE GRADE 1 | 7 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | LIGAMENT SPRAIN GRADE 1 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | FATIGUE GRADE 2 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | ANXIETY GRADE 2 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events During Double-blind Period | OEDEMA PERIPHERAL GRADE 1 | 1 Number of participants |
Secondary
Incidence and Severity of Adverse Events Up to Week 96
Adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) severity grade: 1 = mild, 2 = moderate, 3 = severe and/or requiring medical intervention but not life-threatening, 4 = life-threatening consequences, and 5 = death.
Time frame: Up to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Incidence and Severity of Adverse Events Up to Week 96 | Grade 4 | 7 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events Up to Week 96 | Grade 2 | 63 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events Up to Week 96 | Grade 5 | 3 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events Up to Week 96 | Grade 3 | 21 Number of participants |
| Double-Blind Placebo | Incidence and Severity of Adverse Events Up to Week 96 | Grade 1 | 61 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events Up to Week 96 | Grade 3 | 18 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events Up to Week 96 | Grade 4 | 0 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events Up to Week 96 | Grade 5 | 1 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events Up to Week 96 | Grade 2 | 53 Number of participants |
| Double-Blind Tocilizumab | Incidence and Severity of Adverse Events Up to Week 96 | Grade 1 | 78 Number of participants |
| Placebo, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 3 | 9 Number of participants |
| Placebo, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 1 | 60 Number of participants |
| Placebo, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 2 | 41 Number of participants |
| Placebo, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 4 | 4 Number of participants |
| Placebo, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 5 | 1 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 4 | 5 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 2 | 35 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 1 | 53 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 3 | 8 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Incidence and Severity of Adverse Events Up to Week 96 | Grade 5 | 1 Number of participants |
Secondary
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
A laboratory event occurred if the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade for a post-baseline laboratory measurement increased from baseline.
Time frame: From Baseline up to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High Alkaline Phosphatase | 7 Number of Participants |
| Double-Blind Placebo | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High SGPT/ALT | 17 Number of Participants |
| Double-Blind Placebo | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High SGOT/AST | 17 Number of Participants |
| Double-Blind Placebo | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | Low Neutrophils, Segmented, Abs | 2 Number of Participants |
| Double-Blind Placebo | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | Low Platelet | 0 Number of Participants |
| Double-Blind Placebo | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High Bilirubin | 1 Number of Participants |
| Double-Blind Tocilizumab | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | Low Platelet | 9 Number of Participants |
| Double-Blind Tocilizumab | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High Alkaline Phosphatase | 1 Number of Participants |
| Double-Blind Tocilizumab | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | Low Neutrophils, Segmented, Abs | 27 Number of Participants |
| Double-Blind Tocilizumab | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High SGPT/ALT | 32 Number of Participants |
| Double-Blind Tocilizumab | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High Bilirubin | 13 Number of Participants |
| Double-Blind Tocilizumab | Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period | High SGOT/AST | 24 Number of Participants |
Secondary
Number of Participants With Adverse Events Leading to Death During Double-blind Period
Reason of death is coded using MedDRA 20.1
Time frame: From Baseline up to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death During Double-blind Period | CARDIAC FAILURE CHRONIC | 1 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death During Double-blind Period | MYOCARDITIS | 1 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death During Double-blind Period | MYOCARDIAL INFARCTION | 1 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death During Double-blind Period | DEATH | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death During Double-blind Period | DEATH | 1 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death During Double-blind Period | CARDIAC FAILURE CHRONIC | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death During Double-blind Period | MYOCARDIAL INFARCTION | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death During Double-blind Period | MYOCARDITIS | 0 Number of participants |
Secondary
Number of Participants With Adverse Events Leading to Death Up to Week 96
Time frame: Up to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death Up to Week 96 | DEATH | 0 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death Up to Week 96 | CARDIAC FAILURE CHRONIC | 1 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDIAL INFARCTION | 1 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDITIS | 1 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death Up to Week 96 | BRAIN INJURY | 0 Number of participants |
| Double-Blind Placebo | Number of Participants With Adverse Events Leading to Death Up to Week 96 | PULMONARY HYPERTENSION | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death Up to Week 96 | BRAIN INJURY | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death Up to Week 96 | PULMONARY HYPERTENSION | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDITIS | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDIAL INFARCTION | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death Up to Week 96 | CARDIAC FAILURE CHRONIC | 0 Number of participants |
| Double-Blind Tocilizumab | Number of Participants With Adverse Events Leading to Death Up to Week 96 | DEATH | 1 Number of participants |
| Placebo, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDITIS | 0 Number of participants |
| Placebo, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | BRAIN INJURY | 1 Number of participants |
| Placebo, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | DEATH | 0 Number of participants |
| Placebo, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | CARDIAC FAILURE CHRONIC | 0 Number of participants |
| Placebo, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDIAL INFARCTION | 0 Number of participants |
| Placebo, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | PULMONARY HYPERTENSION | 0 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | PULMONARY HYPERTENSION | 1 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDITIS | 0 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | MYOCARDIAL INFARCTION | 0 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | DEATH | 0 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | BRAIN INJURY | 0 Number of participants |
| Tocilizumab, Then Tocilizumab Open Label | Number of Participants With Adverse Events Leading to Death Up to Week 96 | CARDIAC FAILURE CHRONIC | 0 Number of participants |
Secondary
Percentage of Participants With Change in Digital Ulcer Count at Week 96
A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator.
Time frame: From Baseline to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 1 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by >4 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 3 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Baseline missing | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 4 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 4 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 1 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | No change | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 3 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 2 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 2 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by >4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 3 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | No change | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 1 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 2 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 3 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by >4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 1 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 2 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by >4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Baseline missing | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by >4 | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 2 | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 1 | 3.8 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | No change | 91.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 2 | 2.5 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 1 | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 3 | 1.3 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 4 | 1.3 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 3 | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Baseline missing | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 4 | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by >4 | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 2 | 1.2 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by >4 | 1.2 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 3 | 1.2 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by >4 | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | No change | 83.3 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 1 | 4.8 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 1 | 4.8 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Baseline missing | 1.2 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 4 | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 2 | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Increase by 3 | 1.2 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Percentage of Participants With Change in Digital Ulcer Count at Week 96 | Decrease by 4 | 1.2 Percentage of participants |
Secondary
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | No change | 85.4 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 1 | 3.4 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 2 | 1.1 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 3 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 4 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by >4 | 1.1 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 1 | 3.4 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 2 | 3.4 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 3 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 4 | 1.1 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by >4 | 0 Percentage of participants |
| Double-Blind Placebo | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Baseline missing | 1.1 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by >4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | No change | 87.2 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 1 | 4.3 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 1 | 5.3 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 2 | 1.1 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 2 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 3 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Baseline missing | 1.1 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by 4 | 0 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Decrease by 3 | 1.1 Percentage of participants |
| Double-Blind Tocilizumab | Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period | Increase by >4 | 0 Percentage of participants |
Secondary
Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period
The proportion of participants with threshold improvements in mRSS at Week 48 relative to baseline.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period | ≥ 20% | 50.0 Percentage of Participants |
| Double-Blind Placebo | Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period | ≥ 40% | 37.7 Percentage of Participants |
| Double-Blind Placebo | Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period | ≥ 60% | 22.6 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period | ≥ 20% | 72.1 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period | ≥ 40% | 42.3 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period | ≥ 60% | 17.3 Percentage of Participants |
Comparison: This statistical analysis applies to participants with ≥ 20% improvement in mRSS.p-value: 0.000795% CI: [9.2, 34.6]Cochran-Mantel-Haenszel
Comparison: This statistical analysis applies to participants with ≥ 40% improvement in mRSS.p-value: 0.513995% CI: [-8.7, 17.3]Cochran-Mantel-Haenszel
Comparison: This statistical analysis applies to participants with ≥ 60% improvement in mRSS.p-value: 0.327695% CI: [-16.2, 5.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96
Reported were the percentage of participants with post-baseline treatment-induced anti-TCZ antibodies. Positive samples underwent additional analyses: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype.
Time frame: Open-label period from Week 48 to 96
Population: Safety population: received at least one dose of study drug and provide data from at least one post dose safety assessment. Only samples from the Double Blind TCZ, then Open Label TCZ were measured by the lab after week 48. Data for the Double Blind Period were reported at the time of Primary Results disclosure up to Week 48.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96 | Treatment-Induced Anti-TCZ Antibodies | 0.0 Percentage of Participants |
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96 | Anti-TCZ Antibodies of Neutralizing Potential | 0.0 Percentage of Participants |
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96 | Anti-TCZ Antibodies of IgE | 0.0 Percentage of Participants |
Secondary
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48
Incidence of anti-Tocilizumab antibodies during the study relative to the prevalence of anti-Tocilizumab antibodies at baseline. Samples that are positive for anti-TCZ in the screening assay will be further analyzed by a confirmation assay to confirm specificity. If the confirmation assay is positive, two additional tests will be performed: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype.
Time frame: Double-blind period (up to Week 48)
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive Anti-TCZ Assay | 0.0 Percentage of Participants |
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive Confirmation Assay | 0.0 Percentage of Participants |
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive Neutralizing Assay | 0.0 Percentage of Participants |
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive IgE Assay | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive IgE Assay | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive Anti-TCZ Assay | 2.9 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive Neutralizing Assay | 1.0 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48 | Positive Confirmation Assay | 1.0 Percentage of Participants |
Secondary
Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline
Incidence of anti-Tocilizumab at baseline
Time frame: Baseline
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Placebo | Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline | 5.9 Percentage of Participants |
| Double-Blind Tocilizumab | Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline | 2.9 Percentage of Participants |
Secondary
Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48
Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline up to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Baseline | 7.43 mg/L | Standard Deviation 12.61 |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Week 4 | 9.81 mg/L | Standard Deviation 20.79 |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Week 24 | 9.89 mg/L | Standard Deviation 13.99 |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Week 48 | 7.52 mg/L | Standard Deviation 12.8 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Week 48 | 1.58 mg/L | Standard Deviation 6.22 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Baseline | 9.00 mg/L | Standard Deviation 14.76 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Week 24 | 0.56 mg/L | Standard Deviation 1.19 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48 | Week 4 | 0.85 mg/L | Standard Deviation 2.52 |
Secondary
Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96
Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline up to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Baseline | 7.42 mg/L | Standard Deviation 12.62 |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 4 | 10.05 mg/L | Standard Deviation 20.82 |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 24 | 9.89 mg/L | Standard Deviation 13.99 |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 48 | 7.40 mg/L | Standard Deviation 12.62 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 24 | 0.56 mg/L | Standard Deviation 1.19 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Baseline | 8.99 mg/L | Standard Deviation 14.76 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 4 | 0.85 mg/L | Standard Deviation 2.5 |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 48 | 1.75 mg/L | Standard Deviation 6.43 |
| Placebo, Then Tocilizumab Open Label | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 72 | 0.57 mg/L | Standard Deviation 0.8 |
| Placebo, Then Tocilizumab Open Label | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 96 | 0.90 mg/L | Standard Deviation 2.73 |
| Tocilizumab, Then Tocilizumab Open Label | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 72 | 0.92 mg/L | Standard Deviation 3.61 |
| Tocilizumab, Then Tocilizumab Open Label | Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96 | Week 96 | 0.97 mg/L | Standard Deviation 5.08 |
Secondary
Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48
Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline up to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Baseline | 3.82 mg/L |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Week 4 | 3.71 mg/L |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Week 24 | 4.15 mg/L |
| Double-Blind Placebo | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Week 48 | 3.67 mg/L |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Week 48 | 0.20 mg/L |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Baseline | 4.05 mg/L |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Week 24 | 0.20 mg/L |
| Double-Blind Tocilizumab | Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48 | Week 4 | 0.20 mg/L |
Secondary
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 4 | 1.11 pg/mL | Standard Deviation 28.78 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 8 | 2.43 pg/mL | Standard Deviation 31 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 16 | 3.07 pg/mL | Standard Deviation 31.71 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 24 | 0.13 pg/mL | Standard Deviation 30.63 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 36 | -3.48 pg/mL | Standard Deviation 23.23 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 48 | -1.60 pg/mL | Standard Deviation 21.54 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 36 | 52.26 pg/mL | Standard Deviation 55.81 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 4 | 130.60 pg/mL | Standard Deviation 395.93 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 24 | 53.33 pg/mL | Standard Deviation 46.81 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 8 | 97.22 pg/mL | Standard Deviation 237.43 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 48 | 40.01 pg/mL | Standard Deviation 29.89 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48 | Week 16 | 57.10 pg/mL | Standard Deviation 62.62 |
Secondary
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 8 | 14.21 pg/mL | Standard Deviation 26.82 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 24 | 11.81 pg/mL | Standard Deviation 24.05 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 4 | 13.41 pg/mL | Standard Deviation 29.98 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 36 | 9.32 pg/mL | Standard Deviation 15.23 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 16 | 15.40 pg/mL | Standard Deviation 24.26 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 48 | 9.25 pg/mL | Standard Deviation 15.14 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Baseline | 11.83 pg/mL | Standard Deviation 19.74 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 48 | 53.98 pg/mL | Standard Deviation 57.25 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Baseline | 13.88 pg/mL | Standard Deviation 43.77 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 4 | 143.97 pg/mL | Standard Deviation 427.01 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 8 | 111.44 pg/mL | Standard Deviation 280.34 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 16 | 66.20 pg/mL | Standard Deviation 70.5 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 24 | 62.74 pg/mL | Standard Deviation 53.4 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48 | Week 36 | 62.15 pg/mL | Standard Deviation 68.08 |
Secondary
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: Up to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Baseline | 11.85 pg/mL | Standard Deviation 19.73 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 4 | 13.41 pg/mL | Standard Deviation 29.98 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 8 | 14.21 pg/mL | Standard Deviation 26.82 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 16 | 15.40 pg/mL | Standard Deviation 24.26 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 24 | 11.81 pg/mL | Standard Deviation 24.05 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 36 | 9.32 pg/mL | Standard Deviation 15.23 |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 48 | 9.10 pg/mL | Standard Deviation 14.88 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 8 | 111.44 pg/mL | Standard Deviation 280.34 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 48 | 53.34 pg/mL | Standard Deviation 56.8 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 24 | 62.74 pg/mL | Standard Deviation 53.4 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Baseline | 13.86 pg/mL | Standard Deviation 43.78 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 16 | 66.20 pg/mL | Standard Deviation 70.5 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 4 | 144.75 pg/mL | Standard Deviation 429.14 |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 36 | 62.15 pg/mL | Standard Deviation 68.08 |
| Placebo, Then Tocilizumab Open Label | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 96 | 62.60 pg/mL | Standard Deviation 57.21 |
| Tocilizumab, Then Tocilizumab Open Label | Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96 | Week 96 | 52.03 pg/mL | Standard Deviation 46.51 |
Secondary
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 4 | -0.12 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 8 | 0.83 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 16 | 0.34 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 24 | 0.00 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 36 | 0.00 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 48 | 0.00 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 36 | 41.20 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 4 | 52.41 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 24 | 41.21 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 8 | 52.35 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 48 | 32.96 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48 | Week 16 | 42.35 pg/mL |
Secondary
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 8 | 5.15 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 24 | 3.53 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 4 | 5.31 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 36 | 4.01 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 16 | 5.01 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 48 | 3.85 pg/mL |
| Double-Blind Placebo | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Baseline | 5.21 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 48 | 43.45 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Baseline | 4.65 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 4 | 56.50 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 8 | 58.65 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 16 | 48.25 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 24 | 47.90 pg/mL |
| Double-Blind Tocilizumab | Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48 | Week 36 | 46.30 pg/mL |
Secondary
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 4 | 3.96 ng/mL | Standard Deviation 79 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 8 | 3.31 ng/mL | Standard Deviation 65.47 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 16 | 6.04 ng/mL | Standard Deviation 77.69 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 24 | -1.29 ng/mL | Standard Deviation 35.46 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 36 | -4.31 ng/mL | Standard Deviation 35.92 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 48 | 7.23 ng/mL | Standard Deviation 86.81 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 36 | 544.89 ng/mL | Standard Deviation 142.95 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 4 | 444.23 ng/mL | Standard Deviation 120.9 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 24 | 540.98 ng/mL | Standard Deviation 152.7 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 8 | 501.09 ng/mL | Standard Deviation 140.42 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 48 | 525.66 ng/mL | Standard Deviation 165.53 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48 | Week 16 | 539.21 ng/mL | Standard Deviation 165.63 |
Secondary
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 8 | 45.71 ng/mL | Standard Deviation 57.95 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 24 | 41.35 ng/mL | Standard Deviation 15.17 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 4 | 46.07 ng/mL | Standard Deviation 73.52 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 36 | 38.13 ng/mL | Standard Deviation 11.22 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 16 | 47.81 ng/mL | Standard Deviation 68.22 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 48 | 49.27 ng/mL | Standard Deviation 76.97 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Baseline | 42.16 ng/mL | Standard Deviation 32.41 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 48 | 571.48 ng/mL | Standard Deviation 167.85 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Baseline | 42.22 ng/mL | Standard Deviation 14.56 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 4 | 486.58 ng/mL | Standard Deviation 122.94 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 8 | 546.59 ng/mL | Standard Deviation 142.58 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 16 | 583.87 ng/mL | Standard Deviation 164.36 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 24 | 587.28 ng/mL | Standard Deviation 153.9 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48 | Week 36 | 589.59 ng/mL | Standard Deviation 140.63 |
Secondary
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96
Serum Soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: Up to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Baseline | 42.23 ng/mL | Standard Deviation 32.56 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 4 | 46.07 ng/mL | Standard Deviation 73.52 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 8 | 45.71 ng/mL | Standard Deviation 57.95 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 16 | 47.81 ng/mL | Standard Deviation 68.22 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 24 | 41.35 ng/mL | Standard Deviation 15.17 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 36 | 38.13 ng/mL | Standard Deviation 11.22 |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 48 | 49.51 ng/mL | Standard Deviation 76.17 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 8 | 546.59 ng/mL | Standard Deviation 142.58 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 48 | 566.49 ng/mL | Standard Deviation 175.25 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 24 | 587.28 ng/mL | Standard Deviation 153.9 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Baseline | 42.15 ng/mL | Standard Deviation 14.5 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 16 | 583.87 ng/mL | Standard Deviation 164.36 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 4 | 487.70 ng/mL | Standard Deviation 123.02 |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 36 | 589.59 ng/mL | Standard Deviation 140.63 |
| Placebo, Then Tocilizumab Open Label | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 96 | 558.38 ng/mL | Standard Deviation 256.86 |
| Tocilizumab, Then Tocilizumab Open Label | Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96 | Week 96 | 565.31 ng/mL | Standard Deviation 159.82 |
Secondary
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 4 | 0.20 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 8 | 0.20 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 16 | 0.25 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 24 | 1.20 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 36 | -0.40 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 48 | -0.70 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 36 | 541.70 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 4 | 437.80 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 24 | 547.50 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 8 | 489.90 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 48 | 532.20 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48 | Week 16 | 542.30 ng/mL |
Secondary
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 8 | 37.20 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 24 | 39.30 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 4 | 38.10 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 36 | 36.20 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 16 | 38.95 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 48 | 36.00 ng/mL |
| Double-Blind Placebo | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Baseline | 37.10 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 48 | 576.50 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Baseline | 39.00 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 4 | 482.50 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 8 | 536.00 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 16 | 589.50 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 24 | 590.00 ng/mL |
| Double-Blind Tocilizumab | Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48 | Week 36 | 591.00 ng/mL |
Secondary
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Time frame: From Baseline to Week 48
Population: The PK population includes all patients who received at least one TCZ injection and had at least one PK sample with detectable results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | Baseline | 0.00 ug/mL | Standard Deviation 0.03 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | Week 4 | 30.92 ug/mL | Standard Deviation 15.24 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | Week 8 | 41.82 ug/mL | Standard Deviation 17.66 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | Week 16 | 50.98 ug/mL | Standard Deviation 23.33 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | Week 24 | 54.34 ug/mL | Standard Deviation 26.24 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | Week 36 | 53.55 ug/mL | Standard Deviation 29.25 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, From Baseline to Week 48 | Week 48 | 54.67 ug/mL | Standard Deviation 29.79 |
Secondary
Serum Tocilizumab Concentration, Mean, Up to Week 96
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Time frame: Up to Week 96
Population: The PK population included all participants who received at least one TCZ injection and had at least one PK sample with detectable results. Only samples from the Double Blind TCZ, then Open Label TCZ were measured by the lab after week 48. Data for the Double Blind Period were reported at the time of Primary Results disclosure up to Week 48.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Baseline | 0.00 ug/mL | Standard Deviation 0.03 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Week 4 | 30.76 ug/mL | Standard Deviation 15.23 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Week 8 | 41.82 ug/mL | Standard Deviation 17.66 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Week 16 | 50.98 ug/mL | Standard Deviation 23.33 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Week 24 | 54.34 ug/mL | Standard Deviation 26.24 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Week 36 | 53.55 ug/mL | Standard Deviation 29.25 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Week 48 | 54.87 ug/mL | Standard Deviation 29.69 |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Mean, Up to Week 96 | Week 96 | 49.99 ug/mL | Standard Deviation 26.19 |
Secondary
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Time frame: From Baseline to Week 48
Population: The PK population includes all patients who received at least one TCZ injection and had at least one PK sample with detectable results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Double-Blind Placebo | Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | Baseline | 0.00 ug/mL |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | Week 4 | 28.70 ug/mL |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | Week 8 | 39.25 ug/mL |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | Week 16 | 47.40 ug/mL |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | Week 24 | 52.60 ug/mL |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | Week 36 | 52.50 ug/mL |
| Double-Blind Placebo | Serum Tocilizumab Concentration, Median, From Baseline to Week 48 | Week 48 | 52.10 ug/mL |
Secondary
Summary of Adverse Events During Double-blind Period
Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 20.1. NMSC = Non-Melanoma Skin Cancer
Time frame: From Baseline until Week 48
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Fatal AE | 2.8 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Infections and Infestations AE | 50.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | AE leading to withdrawal from treatment | 10.4 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Opportunistic Infections and Infestations AE | 0.9 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | SAE leading to withdrawal from treatment | 3.8 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Malignancy AE | 0.9 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | AE leading to dose modification/interruption | 25.5 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Malignancy AE (excluding NMSC) | 0.9 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Withdrawn from study due to an AE | 3.8 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Hepatic SAE | 0.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | AE related to study drug | 34.9 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Stroke SAE | 0.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | SAE leading to dose modification/interruption | 6.6 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Myocardial Infarction SAE | 1.9 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Related AE leading to withdrawal from treatment | 1.9 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Anaphylactic Reaction AE | 0.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Serious Adverse Events (SAEs) | 17.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Anaphylactic Reaction AE (Sampson's Criteria) | 0.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Related AE with dose modification/interruption | 16.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Gastrointestinal Perforation SAE | 0.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | SAE related to study drug | 6.6 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Bleeding SAE | 0.9 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | Infections and Infestations SAE | 6.6 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Demyelinating SAE | 0.0 Percentage of Participants |
| Double-Blind Placebo | Summary of Adverse Events During Double-blind Period | At least one Adverse Event (AE) | 77.4 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Demyelinating SAE | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Adverse Event (AE) | 85.6 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Withdrawn from study due to an AE | 2.9 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Fatal AE | 1.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Serious Adverse Events (SAEs) | 12.5 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | SAE leading to withdrawal from treatment | 3.8 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | SAE leading to dose modification/interruption | 2.9 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | SAE related to study drug | 1.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | AE leading to withdrawal from treatment | 5.8 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | AE leading to dose modification/interruption | 19.2 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | AE related to study drug | 46.2 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Related AE leading to withdrawal from treatment | 1.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Related AE with dose modification/interruption | 11.5 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Infections and Infestations SAE | 1.9 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Infections and Infestations AE | 51.9 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Opportunistic Infections and Infestations AE | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Malignancy AE | 1.9 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Malignancy AE (excluding NMSC) | 1.9 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Hepatic SAE | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Stroke SAE | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Myocardial Infarction SAE | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Anaphylactic Reaction AE | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | Anaphylactic Reaction AE (Sampson's Criteria) | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Gastrointestinal Perforation SAE | 0.0 Percentage of Participants |
| Double-Blind Tocilizumab | Summary of Adverse Events During Double-blind Period | At least one Bleeding SAE | 0.0 Percentage of Participants |
Secondary
Summary of Adverse Events Up to Week 96
Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 21.1. NMSC = Non-Melanoma Skin Cancer
Time frame: Up to Week 96
Population: The analysis was conducted in the safety population i.e. received at least one dose of study drug and provide data from at least one post dose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | SAE related to study drug | 6.6 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | SAE leading to dose modification/interruption | 5.7 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Infections and Infestations AEs | 6.6 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Related AE with dose modification/interruption | 17.0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | AE leading to withdrawal from treatment | 12.3 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs (Sampson's Criteria) | 0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Related AE leading to withdrawal from treatment | 1.9 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Stroke AEs | 0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | AE leading to dose modification/interruption | 26.4 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | SAE leading to withdrawal from treatment | 5.7 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | AE related to study drug | 34.0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Fatal AE | 2.8 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Withdrawn from study due to an AE | 12.3 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Gastrointestinal Perforation AEs | 0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs | 0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Malignancy AEs (excluding NMSC) | 0.9 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | At least one Adverse Event (AE) | 77.4 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Bleeding AEs | 0.9 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Malignancy AEs | 0.9 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Opportunistic Infections AEs | 0.9 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Myocardial Infarction AEs | 1.9 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Demyelinating AEs | 0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Hepatic AEs | 0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Infections and Infestations AEs | 50.0 Percentage of participants |
| Double-Blind Placebo | Summary of Adverse Events Up to Week 96 | Serious Adverse Events (SAEs) | 17.0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Bleeding AEs | 0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Myocardial Infarction AEs | 0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs | 0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs (Sampson's Criteria) | 0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | SAE leading to dose modification/interruption | 2.9 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Gastrointestinal Perforation AEs | 0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Withdrawn from study due to an AE | 6.7 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Demyelinating AEs | 0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | SAE related to study drug | 1.0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | AE leading to withdrawal from treatment | 6.7 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | At least one Adverse Event (AE) | 85.6 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | AE leading to dose modification/interruption | 19.2 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | AE related to study drug | 46.2 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Fatal AE | 1.0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Related AE leading to withdrawal from treatment | 1.0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Related AE with dose modification/interruption | 11.5 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Infections and Infestations AEs | 1.9 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Infections and Infestations AEs | 52.9 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Adverse Events (SAEs) | 12.5 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Opportunistic Infections AEs | 1.0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Malignancy AEs | 1.9 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Malignancy AEs (excluding NMSC) | 1.9 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Hepatic AEs | 0 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | SAE leading to withdrawal from treatment | 4.8 Percentage of participants |
| Double-Blind Tocilizumab | Summary of Adverse Events Up to Week 96 | Serious Stroke AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Infections and Infestations AEs | 3.4 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | AE related to study drug | 33.7 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Demyelinating AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs (Sampson's Criteria) | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Infections and Infestations AEs | 46.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Bleeding AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Myocardial Infarction AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Opportunistic Infections AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Adverse Events (SAEs) | 7.9 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | SAE leading to withdrawal from treatment | 1.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Hepatic AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | AE leading to dose modification/interruption | 28.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Malignancy AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | SAE leading to dose modification/interruption | 4.5 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | AE leading to withdrawal from treatment | 1.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Gastrointestinal Perforation AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Related AE leading to withdrawal from treatment | 1.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Fatal AE | 1.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Withdrawn from study due to an AE | 1.1 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Stroke AEs | 0 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Related AE with dose modification/interruption | 12.4 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | At least one Adverse Event (AE) | 77.5 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | SAE related to study drug | 3.4 Percentage of participants |
| Placebo, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Malignancy AEs (excluding NMSC) | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Demyelinating AEs | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | At least one Adverse Event (AE) | 71.7 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Withdrawn from study due to an AE | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Fatal AE | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Adverse Events (SAEs) | 10.9 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | SAE leading to withdrawal from treatment | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | SAE leading to dose modification/interruption | 3.3 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | SAE related to study drug | 3.3 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | AE leading to withdrawal from treatment | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | AE leading to dose modification/interruption | 22.8 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | AE related to study drug | 34.8 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Related AE leading to withdrawal from treatment | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Related AE with dose modification/interruption | 14.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Infections and Infestations AEs | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Infections and Infestations AEs | 39.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Opportunistic Infections AEs | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Malignancy AEs | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Malignancy AEs (excluding NMSC) | 1.1 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Hepatic AEs | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Stroke AEs | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Myocardial Infarction AEs | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Anaphylactic Reaction AEs (Sampson's Criteria) | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Gastrointestinal Perforation AEs | 0 Percentage of participants |
| Tocilizumab, Then Tocilizumab Open Label | Summary of Adverse Events Up to Week 96 | Serious Bleeding AEs | 0 Percentage of participants |
Secondary
Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period
Time to treatment failure is defined as the time from randomization to the time of death, decline in percent-predicted FVC \> 10% relative to baseline, \> 20% increase in mRSS and an increase in mRSS of equal to or more than 5 points, or occurrence of a predefined SSc-related complication as adjudicated by the Clinical Adjudication Committee (whichever occurs first) during the 48-week double-blind treatment period. The median TTF was not estimable and is not presented for either treatment arm because of the low number of patients with events at Week 48.
Time frame: From Baseline to Week 48
Population: The analysis was conducted in the Intent-to-treat (ITT) population, i.e. all patients who were randomized and received any study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-Blind Placebo | Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period | NA months |
| Double-Blind Tocilizumab | Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period | NA months |
p-value: 0.082195% CI: [0.37, 1.06]Cox-proportional hazards model