Rheumatoid Arthritis
Conditions
Brief summary
This single-arm, open-label, multicenter study evaluated the safety and tolerability and the efficacy in reducing disease activity of tocilizumab \[RoActemra/Actemra\] as monotherapy or in combination with methotrexate in patients with active moderate to severe rheumatoid arthritis (RA). Patients were eligible to participate in this study if they are currently experiencing an inadequate response to a stable dose of a non-biologic disease-modifying antirheumatic drug (DMARD). Patients received 8 mg/kg tocilizumab \[RoActemra/Actemra\] as an intravenous infusion every 4 weeks for a total of 6 infusions. The anticipated time on study treatment was 24 weeks. The target sample size was 50-200 patients.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8 mg/kg intravenous infusion every 4 weeks.
DRUGMethotrexate
methotrexate as per standard of care in clinical practice.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients ≥ 18 years of age * Moderate to severe rheumatoid arthritis (RA) for at least 6 months (defined as a Disease Activity Score (DAS28) \> 3.2 at screening) * Patients with active RA after more than 12 weeks of treatment with DMARDs * Patients with inadequate response to a stable dose of non-biologic DMARD
Exclusion criteria
* Autoimmune disease other than RA. Patients with interstitial pulmonary fibrosis and able to tolerate methotrexate (MTX) and patients with Sjögren's Syndrome and RA are permitted * Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment * Prior history of or current inflammatory joint disease other than RA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, 24) | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2. |
| Time to DAS28 Low Disease Activity | 24 Weeks | Time to DAS28 Low Disease Activity was defined as the time in days from the first infusion of study drug to the achievement of a DAS28 Score \<3.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to DAS28 Clinically Significant Improvement | 24 Weeks | Time to DAS28 Clinically Significant Improvement was the Time in days from the first infusion of study drug to the achievement of a DAS28 score reduction of at least 1.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2. |
| Percentage of Participants Achieving DAS28 Remission | Weeks 4, 8, 12, 16, 20, 24 | DAS28 Remission was defined as a DAS28 score \< 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. |
| Time to DAS28 Remission | 24 Weeks | Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score \< 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. |
| Disease Activity Score 28 (DAS28) | Weeks 4, 8, 12, 16, 20, 24 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2. |
| C-Reactive Protein (CRP) | Weeks 4, 8, 12, 16, 20, 24 | Blood was collected for C-Reactive Protein (CRP), a test for inflammation, at Weeks 4, 8, 12, 16, 20 and 24 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). |
| Erythrocyte Sedimentation Rate (ESR) | Weeks 4, 8, 12, 16, 20, 24 | Blood was collected for Erythrocyte Sedimentation Rate (ESR), a test to assess inflammation, at Weeks 4, 8, 12, 16, 20, 24 and was analyzed at a central laboratory. ESR was measured in millimeters/hour (mm/hr). |
| Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 | Blood samples were collected for High Density Lipoprotein (HDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the HDL Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Low (\< 40) or High (≥ 60). The number of participants with category High at each time-point is reported. |
| Number of Participants With AE and SAE Related Discontinuation | 24 Weeks | The number of participants who stopped using the study drug because of an AE or a SAE. An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. |
| Number of Participants With Serious Infections | 24 Weeks | A serious infection was an infection that qualified as a Serious Adverse Event (SAE). A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. |
| Number of Participants With Elevated AST (SGOT) and ALT (SGPT) | Week 24 | Blood was collected for aspartate aminotransferase (serum glutamic oxaloacetic transaminase) \[AST/SGOT\] and alanine aminotransferase (serum glutamic pyruvic transaminase) \[ALT/SGPT\], liver function tests, and were analyzed at a central laboratory. The number of participants with High AST (SGOT) or ALT (SGPT) levels at Week 24 is reported. |
| Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 | Blood samples were collected for Total Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Desirable ( \< 200), Borderline High (200- 239) or High (≥ 240). The number of participants categorized Borderline High or High at each time-point is reported. |
| Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 | Blood samples were collected for Low Density Lipoprotein (LDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the LDL Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Optimal (\< 100), Near Optimal/Above Optimal (100- 129), Borderline High (130- 159), High (160-189) or Very High (≥ 190). The number of participants categorized Borderline High, High or Very High at each time-point is reported. |
| Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24 | Blood samples were collected for Triglyceride and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Triglyceride level in milligram/deciliter (mg/dL) was categorized as: Normal (\< 150), Borderline High (150- 199), High (200- 499) or Very High (≥ 500). The number of participants categorized Borderline High, High or Very High at each time-point is reported. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 24 Weeks | An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. |
| Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Baseline, Weeks 4, 8, 12, 16, 20, 24 | DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. |
Countries
Egypt
Participant flow
Recruitment details
107 participants were enrolled from 11 centers in Egypt, 2 centers were prematurely terminated.
Pre-assignment details
Patients in this 1 arm tocilizumab study were divided into 2 groups: tocilizumab monotherapy or tocilizumab plus methotrexate (patients taking disease-modifying antirheumatic drugs at Baseline who continued concomitant treatment with methotrexate as per standard of care at the investigator's discretion).
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Monotherapy Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). | 30 |
| Tocilizumab + MTX Participants received an 8 mg/kg tocilizumab intravenous (IV) infusion once every 4 weeks for 24 weeks (6 infusions). Participants taking concomitant methotrexate (MTX) at Baseline remained on a stable dose as per standard of care at the Investigator's discretion. | 77 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Investigator's request | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Miscellaneous reason | 0 | 1 |
| Overall Study | Patient withdrew consent | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 4 |
Baseline characteristics
| Characteristic | Tocilizumab Monotherapy | Tocilizumab + MTX | Total |
|---|---|---|---|
| Age, Continuous | 37.78 years STANDARD_DEVIATION 12.47 | 41.76 years STANDARD_DEVIATION 11.84 | 40.64 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 23 Participants | 69 Participants | 92 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 29 | 76 / 76 |
| serious Total, serious adverse events | 5 / 29 | 12 / 76 |
Outcome results
Primary
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2.
Time frame: Baseline to Week 24 (Weeks 4, 8, 12, 16, 20, 24)
Population: Intent-to-treat (ITT) population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward was applied for missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 4 | 27.59 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 8 | 34.48 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 12 | 34.48 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 16 | 44.83 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 20 | 62.07 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 24 | 58.62 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 20 | 57.89 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 4 | 18.42 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 16 | 47.37 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 8 | 40.79 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 24 | 59.21 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Low Disease Activity | Week 12 | 38.16 percentage of participants |
Primary
Time to DAS28 Low Disease Activity
Time to DAS28 Low Disease Activity was defined as the time in days from the first infusion of study drug to the achievement of a DAS28 Score \<3.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2.
Time frame: 24 Weeks
Population: Intent-to-treat population included all participants who received at least one dose of study drug and had data for at least one follow-up variable available. Last observation carried forward.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tocilizumab | Time to DAS28 Low Disease Activity | 107.2 days |
| Tocilizumab + MTX | Time to DAS28 Low Disease Activity | 100.2 days |
Secondary
C-Reactive Protein (CRP)
Blood was collected for C-Reactive Protein (CRP), a test for inflammation, at Weeks 4, 8, 12, 16, 20 and 24 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL).
Time frame: Weeks 4, 8, 12, 16, 20, 24
Population: Participants from the intent-to-treat population, all participants who received study drug and had data for at least one follow-up variable, with data available for the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | C-Reactive Protein (CRP) | Week 16 | 4.38 mg/L | Standard Deviation 9.98 |
| Tocilizumab | C-Reactive Protein (CRP) | Week 12 | 9.35 mg/L | Standard Deviation 17.29 |
| Tocilizumab | C-Reactive Protein (CRP) | Week 20 | 7.92 mg/L | Standard Deviation 15.07 |
| Tocilizumab | C-Reactive Protein (CRP) | Week 24 | 6.99 mg/L | Standard Deviation 13.64 |
| Tocilizumab | C-Reactive Protein (CRP) | Week 4 | 13.04 mg/L | Standard Deviation 24.9 |
| Tocilizumab | C-Reactive Protein (CRP) | Week 8 (n=25,74) | 14.74 mg/L | Standard Deviation 35.74 |
| Tocilizumab + MTX | C-Reactive Protein (CRP) | Week 4 | 12.28 mg/L | Standard Deviation 28.37 |
| Tocilizumab + MTX | C-Reactive Protein (CRP) | Week 24 | 3.82 mg/L | Standard Deviation 13.39 |
| Tocilizumab + MTX | C-Reactive Protein (CRP) | Week 12 | 6.89 mg/L | Standard Deviation 15.84 |
| Tocilizumab + MTX | C-Reactive Protein (CRP) | Week 16 | 3.87 mg/L | Standard Deviation 11.01 |
| Tocilizumab + MTX | C-Reactive Protein (CRP) | Week 8 (n=25,74) | 6.24 mg/L | Standard Deviation 13.39 |
| Tocilizumab + MTX | C-Reactive Protein (CRP) | Week 20 | 4.20 mg/L | Standard Deviation 12.11 |
Secondary
Disease Activity Score 28 (DAS28)
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2.
Time frame: Weeks 4, 8, 12, 16, 20, 24
Population: Participants from the intent-to-treat population, all participants who received study drug and had at least 1 follow-up variable, with data available at the given time-point. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Disease Activity Score 28 (DAS28) | Week 8 | 3.72 score on a scale | Standard Deviation 1.71 |
| Tocilizumab | Disease Activity Score 28 (DAS28) | Week 12 | 3.37 score on a scale | Standard Deviation 1.62 |
| Tocilizumab | Disease Activity Score 28 (DAS28) | Week 16 | 3.25 score on a scale | Standard Deviation 1.54 |
| Tocilizumab | Disease Activity Score 28 (DAS28) | Week 4 (n=24,75) | 4.17 score on a scale | Standard Deviation 1.45 |
| Tocilizumab | Disease Activity Score 28 (DAS28) | Week 20 | 2.86 score on a scale | Standard Deviation 1.5 |
| Tocilizumab | Disease Activity Score 28 (DAS28) | Week 24 | 2.51 score on a scale | Standard Deviation 1.5 |
| Tocilizumab + MTX | Disease Activity Score 28 (DAS28) | Week 20 | 3.11 score on a scale | Standard Deviation 1.44 |
| Tocilizumab + MTX | Disease Activity Score 28 (DAS28) | Week 8 | 3.68 score on a scale | Standard Deviation 1.6 |
| Tocilizumab + MTX | Disease Activity Score 28 (DAS28) | Week 4 (n=24,75) | 4.48 score on a scale | Standard Deviation 1.47 |
| Tocilizumab + MTX | Disease Activity Score 28 (DAS28) | Week 12 | 3.54 score on a scale | Standard Deviation 1.45 |
| Tocilizumab + MTX | Disease Activity Score 28 (DAS28) | Week 24 | 3.06 score on a scale | Standard Deviation 1.51 |
| Tocilizumab + MTX | Disease Activity Score 28 (DAS28) | Week 16 | 3.21 score on a scale | Standard Deviation 1.43 |
Secondary
Erythrocyte Sedimentation Rate (ESR)
Blood was collected for Erythrocyte Sedimentation Rate (ESR), a test to assess inflammation, at Weeks 4, 8, 12, 16, 20, 24 and was analyzed at a central laboratory. ESR was measured in millimeters/hour (mm/hr).
Time frame: Weeks 4, 8, 12, 16, 20, 24
Population: Participants from the intent-to-treat population, all participants who received study drug and had at least 1 follow-up variable, with data available at the given time point. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Week 4 (n=24,27) | 21.08 mm/hr | Standard Deviation 22.27 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Week 8 | 17.18 mm/hr | Standard Deviation 21.54 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Week 12 | 14.12 mm/hr | Standard Deviation 15.1 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Week 16 | 15.80 mm/hr | Standard Deviation 23.65 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Week 20 | 16.32 mm/hr | Standard Deviation 25.44 |
| Tocilizumab | Erythrocyte Sedimentation Rate (ESR) | Week 24 | 16.32 mm/hr | Standard Deviation 22.43 |
| Tocilizumab + MTX | Erythrocyte Sedimentation Rate (ESR) | Week 20 | 14.28 mm/hr | Standard Deviation 20.42 |
| Tocilizumab + MTX | Erythrocyte Sedimentation Rate (ESR) | Week 4 (n=24,27) | 20.37 mm/hr | Standard Deviation 25.66 |
| Tocilizumab + MTX | Erythrocyte Sedimentation Rate (ESR) | Week 16 | 13.88 mm/hr | Standard Deviation 18.02 |
| Tocilizumab + MTX | Erythrocyte Sedimentation Rate (ESR) | Week 8 | 13.79 mm/hr | Standard Deviation 18.52 |
| Tocilizumab + MTX | Erythrocyte Sedimentation Rate (ESR) | Week 24 | 16.40 mm/hr | Standard Deviation 22.26 |
| Tocilizumab + MTX | Erythrocyte Sedimentation Rate (ESR) | Week 12 | 16.41 mm/hr | Standard Deviation 22.25 |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time frame: 24 Weeks
Population: Safety population included all participants who received study drug and had post-dose safety data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 29 participants |
| Tocilizumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 participants |
| Tocilizumab + MTX | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 76 participants |
| Tocilizumab + MTX | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 12 participants |
Secondary
Number of Participants With AE and SAE Related Discontinuation
The number of participants who stopped using the study drug because of an AE or a SAE. An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time frame: 24 Weeks
Population: Safety population included all participants who received study drug and had post-dose safety data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With AE and SAE Related Discontinuation | Discontinuation due to AE | 8 participants |
| Tocilizumab | Number of Participants With AE and SAE Related Discontinuation | Discontinuation due to SAE | 5 participants |
| Tocilizumab + MTX | Number of Participants With AE and SAE Related Discontinuation | Discontinuation due to AE | 7 participants |
| Tocilizumab + MTX | Number of Participants With AE and SAE Related Discontinuation | Discontinuation due to SAE | 6 participants |
Secondary
Number of Participants With Elevated AST (SGOT) and ALT (SGPT)
Blood was collected for aspartate aminotransferase (serum glutamic oxaloacetic transaminase) \[AST/SGOT\] and alanine aminotransferase (serum glutamic pyruvic transaminase) \[ALT/SGPT\], liver function tests, and were analyzed at a central laboratory. The number of participants with High AST (SGOT) or ALT (SGPT) levels at Week 24 is reported.
Time frame: Week 24
Population: Participants from the safety population, all participants who received study drug and had at least 1 post-dose safety assessment, with data available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Elevated AST (SGOT) and ALT (SGPT) | ALT (SGPT) | 3 participants |
| Tocilizumab | Number of Participants With Elevated AST (SGOT) and ALT (SGPT) | AST (SGOT) | 3 participants |
| Tocilizumab + MTX | Number of Participants With Elevated AST (SGOT) and ALT (SGPT) | ALT (SGPT) | 6 participants |
| Tocilizumab + MTX | Number of Participants With Elevated AST (SGOT) and ALT (SGPT) | AST (SGOT) | 8 participants |
Secondary
Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines
Blood samples were collected for High Density Lipoprotein (HDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the HDL Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Low (\< 40) or High (≥ 60). The number of participants with category High at each time-point is reported.
Time frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24
Population: Safety population included all participants who received study drug and had post-dose safety data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 12 | 6 participants |
| Tocilizumab | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 20 | 2 participants |
| Tocilizumab | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 8 | 2 participants |
| Tocilizumab | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 24 | 5 participants |
| Tocilizumab | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 0 | 4 participants |
| Tocilizumab | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 16 | 5 participants |
| Tocilizumab | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 4 | 10 participants |
| Tocilizumab + MTX | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 24 | 20 participants |
| Tocilizumab + MTX | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 4 | 34 participants |
| Tocilizumab + MTX | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 8 | 26 participants |
| Tocilizumab + MTX | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 12 | 22 participants |
| Tocilizumab + MTX | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 16 | 19 participants |
| Tocilizumab + MTX | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 20 | 20 participants |
| Tocilizumab + MTX | Number of Participants With Elevated HDL Cholesterol According to ATPIII Guidelines | Week 0 | 20 participants |
Secondary
Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines
Blood samples were collected for Low Density Lipoprotein (LDL) Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the LDL Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Optimal (\< 100), Near Optimal/Above Optimal (100- 129), Borderline High (130- 159), High (160-189) or Very High (≥ 190). The number of participants categorized Borderline High, High or Very High at each time-point is reported.
Time frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24
Population: Safety population included all participants who received study drug and had post-dose safety data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 20 | 7 participants |
| Tocilizumab | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 4 | 11 participants |
| Tocilizumab | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 16 | 9 participants |
| Tocilizumab | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 8 | 7 participants |
| Tocilizumab | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 24 | 8 participants |
| Tocilizumab | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 12 | 8 participants |
| Tocilizumab | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 0 | 9 participants |
| Tocilizumab + MTX | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 24 | 29 participants |
| Tocilizumab + MTX | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 16 | 31 participants |
| Tocilizumab + MTX | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 20 | 33 participants |
| Tocilizumab + MTX | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 0 | 24 participants |
| Tocilizumab + MTX | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 4 | 35 participants |
| Tocilizumab + MTX | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 8 | 21 participants |
| Tocilizumab + MTX | Number of Participants With Elevated LDL Cholesterol According to ATPIII Guidelines | Week 12 | 27 participants |
Secondary
Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines
Blood samples were collected for Total Cholesterol and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Total Cholesterol level in milligram/deciliter (mg/dL) was categorized as: Desirable ( \< 200), Borderline High (200- 239) or High (≥ 240). The number of participants categorized Borderline High or High at each time-point is reported.
Time frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24
Population: Safety population included all participants who received study drug and had post-dose safety data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 8 | 10 participants |
| Tocilizumab | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 16 | 10 participants |
| Tocilizumab | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 4 | 16 participants |
| Tocilizumab | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 20 | 7 participants |
| Tocilizumab | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 12 | 9 participants |
| Tocilizumab | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 24 | 9 participants |
| Tocilizumab | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 0 | 10 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 24 | 30 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 0 | 25 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 4 | 41 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 8 | 34 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 12 | 30 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 16 | 36 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Total Cholesterol According to ATPIII Guidelines | Week 20 | 35 participants |
Secondary
Number of Participants With Elevated Triglyceride According to ATPIII Guidelines
Blood samples were collected for Triglyceride and were sent to a central laboratory for analysis. According to Adult Treatment Profile III (ATPIII) guidelines the Triglyceride level in milligram/deciliter (mg/dL) was categorized as: Normal (\< 150), Borderline High (150- 199), High (200- 499) or Very High (≥ 500). The number of participants categorized Borderline High, High or Very High at each time-point is reported.
Time frame: Weeks 0 (Baseline), 4, 8, 12, 16, 20, 24
Population: Safety population included all participants who received study drug and had post-dose safety data available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 20 | 8 participants |
| Tocilizumab | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 8 | 4 participants |
| Tocilizumab | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 24 | 6 participants |
| Tocilizumab | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 0 | 4 participants |
| Tocilizumab | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 16 | 6 participants |
| Tocilizumab | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 4 | 6 participants |
| Tocilizumab | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 12 | 5 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 24 | 16 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 8 | 12 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 12 | 15 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 16 | 15 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 20 | 16 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 0 | 7 participants |
| Tocilizumab + MTX | Number of Participants With Elevated Triglyceride According to ATPIII Guidelines | Week 4 | 15 participants |
Secondary
Number of Participants With Serious Infections
A serious infection was an infection that qualified as a Serious Adverse Event (SAE). A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time frame: 24 Weeks
Population: Safety population included all participants who received study drug and had post-dose safety data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With Serious Infections | 1 participants |
| Tocilizumab + MTX | Number of Participants With Serious Infections | 1 participants |
Secondary
Percentage of Participants Achieving DAS28 Clinically Significant Improvement
DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24
Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 4 | 62.07 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 8 | 75.86 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 12 | 75.86 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 20 | 82.76 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 24 | 86.20 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 16 | 79.31 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 16 | 92.11 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 4 | 73.68 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 24 | 96.10 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 8 | 86.84 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 12 | 90.79 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Clinically Significant Improvement | Week 20 | 90.79 percentage of participants |
Secondary
Percentage of Participants Achieving DAS28 Remission
DAS28 Remission was defined as a DAS28 score \< 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Time frame: Weeks 4, 8, 12, 16, 20, 24
Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving DAS28 Remission | Week 4 | 17.24 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Remission | Week 8 | 31.03 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Remission | Week 16 | 34.48 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Remission | Week 20 | 41.38 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Remission | Week 12 | 31.03 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving DAS28 Remission | Week 24 | 48.28 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Remission | Week 20 | 40.79 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Remission | Week 4 | 9.21 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Remission | Week 24 | 40.79 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Remission | Week 8 | 23.68 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Remission | Week 16 | 34.21 percentage of participants |
| Tocilizumab + MTX | Percentage of Participants Achieving DAS28 Remission | Week 12 | 27.63 percentage of participants |
Secondary
Time to DAS28 Clinically Significant Improvement
Time to DAS28 Clinically Significant Improvement was the Time in days from the first infusion of study drug to the achievement of a DAS28 score reduction of at least 1.2 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Low Disease Activity was defined as a DAS28 score of \< 3.2.
Time frame: 24 Weeks
Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tocilizumab | Time to DAS28 Clinically Significant Improvement | 59.9 days |
| Tocilizumab + MTX | Time to DAS28 Clinically Significant Improvement | 41.6 days |
Secondary
Time to DAS28 Remission
Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score \< 2.6 units. The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Time frame: 24 Weeks
Population: Intent-to-treat population included all participants who received study drug and had at least 1 follow-up variable. Last observation carried forward.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tocilizumab | Time to DAS28 Remission | 115.9 days |
| Tocilizumab + MTX | Time to DAS28 Remission | 120.5 days |