Arthritis, Rheumatoid
Conditions
Brief summary
This multicenter, open-label, single-arm extension study will evaluate the long-term safety of tocilizumab (RoActemra/Actemra) in participants with RA. Participants who have completed the MA21488 (NCT00810199) core study and the ML21530 (NCT00754572) study and who could benefit from the study drug, according to the opinion of the investigator, will receive 8 milligrams per kilogram (mg/kg) of intravenous (IV) tocilizumab every 4 weeks. The anticipated time on study treatment is 104 weeks.
Interventions
DRUGDMARDs
DMARDs may be added to the tocilizumab treatment in any visit, at the discretion of the investigator, according to the local prescription information and participant's tolerance. Study protocol does not specify any particular DMARD.
DRUGTocilizumab
Tocilizumab will be administered at 8 mg/kg IV dose every 4 weeks for 104 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who have completed their last visit in the core studies ML21530 and MA21488 and that might benefit from treatment using the study drug according to the investigator's evaluation * Absence of an AE or current or recent laboratory finding that would prevent the use of the 8 mg/kg dose of the tocilizumab * Receiving outpatient treatment * For women who are not postmenopausal and are not surgically sterile: agreement to use at least one adequate method of contraception
Exclusion criteria
* Participants who have prematurely discontinued the core studies ML21530 and MA21488 for any reason * MA21488 study participants who remained untreated with tocilizumab after it's discontinuation according to the treatment-free remission criteria of MA21488 study * Immunization with a live/attenuated vaccine since the last administration of the study drug in the core studies ML21530 and ML21488 * Diagnosis after the last visit of the study ML21530 or after the last visit of the study MA21488 of a rheumatic autoimmune disease other than RA, including systemic erythematous lupus (SEL), mixed connective tissue disease (MCTD), scleroderma and polymyositis, or a significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjogren's Syndrome and/or nodulosis with RA are allowed * Diagnosis after the last visit of the core study ML21530 or of the study MA21488 of an inflammatory joint disease other than RA * Abnormal laboratory parameters at the baseline * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * Evidences of a concomitant, serious and uncontrolled illness * Known active condition or a history of recurrent infections by bacteria, viruses, fungi, mycobacteria or other agents * Evidence of an active malignant disease, malignancies diagnosed in the last 10 years or breast cancer diagnosed in the last 20 years * Uncontrolled disease status, such as asthma or inflammatory bowel disease in which acute crises are usually treated with oral or parenteral corticosteroids * Current hepatic disease, as determined by the investigator * Active tuberculosis (TB) requiring treatment in the previous three years. Participants should be screened for latent TB according to local practice guidelines and should not be admitted into the study if latent TB is detected. Participants must not present any evidence of active TB infection at the enrollment. Participants treated for tuberculosis without recurrence in three years are allowed * History of alcohol, drugs or chemical abuse since the inclusion in the core studies ML21530 and MA21488
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs) | From Baseline up to approximately 2 years | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; significant medical event, according to the investigator discretion (e.g., may represent a risk to the participant or may require medical/surgical intervention to prevent one of the outcomes mentioned above). |
| Number of Participants With AEs Leading to Dose Modification or Study Discontinuation | From Baseline up to approximately 2 years | — |
| Number of Participants With AEs of Special Interest | From Baseline up to approximately 2 years | Adverse events of special interest included following events: Infections (including opportunistic infections); myocardial infarction / acute coronary syndrome; gastrointestinal (GI) perforations and related events; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; hemorrhagic events; and hepatic events. Overall number of participants who experienced any of these AEs of special interest was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global Evaluation of Disease Activity by the Participant Using VAS Score | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | Participant's global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as inactive disease (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as disease maximum activity (maximum activity of arthritis). The participant marked the line according to their assessment and the distance from the left edge was measured. |
| Global Evaluation of Disease Activity by the Physician Using VAS Score | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | Physician global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as inactive disease (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as disease maximum activity (maximum activity of arthritis). The physician marked the line according to their assessment and the distance from the left edge was measured. |
| Participant's Pain Assessment Using VAS Score | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | Participant's pain assessment was made on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as no pain and 100 mm (right end of the line) as unbearable pain. The participant marked the line according to their assessment and the distance from the left edge was measured. |
| Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and follow-up (FU) Visit 1 (Week 108), FU Visit 2 (Week 116) | DAS28 score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), participant's global assessment of disease activity (general health \[GH\]) using visual analog scale (VAS), 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (erythrocyte sedimentation rate \[ESR\] in millimeters per hour \[mm/hr\]) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28 = \[0.56 multiplied by (\*) square root (√) of TJC28\] plus (+) \[0.28\*√SJC28\]+\[0.70\*the natural logarithm (ln) ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. |
| Health Assessment Questionnaire (HAQ) Pain VAS Score | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | The HAQ pain VAS is a measure of pain on a continuous 100 mm scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 mm (severe pain). |
| C-Reactive Protein (CRP) Level | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | CRP is an acute phase reactant and is a measure of inflammation. |
| ESR Level | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | ESR is an acute phase reactant and is a measure of inflammation. |
| Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/personal care, ability to stand-up, eating, walking, hygiene, reaching, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents 'no disability' and 3 represents 'very severe, high-dependency disability'. |
| Tender Joint Count (TJC) | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | An assessment of 28 joints was conducted for tenderness. Joints were assessed and classified as tender/not tender by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for tenderness. |
| Swollen Joint Count (SJC) | Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116) | An assessment of 28 joints was conducted for swelling. Joints were assessed and classified as swollen/not swollen by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for swelling. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 104 weeks. The maximum single dose administered to any participant was 800 mg of tocilizumab. Participants might have also received DMARDs in addition to the tocilizumab treatment in any visit, at the investigator discretion, according to the local prescription information and participant's tolerance. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 56.0 years STANDARD_DEVIATION 12.6 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 26 |
| serious Total, serious adverse events | 4 / 26 |
Outcome results
Primary
Number of Participants With AEs Leading to Dose Modification or Study Discontinuation
Time frame: From Baseline up to approximately 2 years
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With AEs Leading to Dose Modification or Study Discontinuation | AEs leading to dose modification | 7 participants |
| Tocilizumab | Number of Participants With AEs Leading to Dose Modification or Study Discontinuation | AEs leading to study discontinuation | 1 participants |
Primary
Number of Participants With AEs of Special Interest
Adverse events of special interest included following events: Infections (including opportunistic infections); myocardial infarction / acute coronary syndrome; gastrointestinal (GI) perforations and related events; malignancies; anaphylaxis/hypersensitivity reactions; demyelinating disorders; stroke; hemorrhagic events; and hepatic events. Overall number of participants who experienced any of these AEs of special interest was reported.
Time frame: From Baseline up to approximately 2 years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants With AEs of Special Interest | 0 participants |
Primary
Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs)
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; significant medical event, according to the investigator discretion (e.g., may represent a risk to the participant or may require medical/surgical intervention to prevent one of the outcomes mentioned above).
Time frame: From Baseline up to approximately 2 years
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs) | SAEs | 4 participants |
| Tocilizumab | Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (NSAEs) | NSAEs | 24 participants |
Secondary
C-Reactive Protein (CRP) Level
CRP is an acute phase reactant and is a measure of inflammation.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 12 (n=26) | 3.13 milligrams per deciliter (mg/dL) | Standard Deviation 6.17 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 24 (n=25) | 1.08 milligrams per deciliter (mg/dL) | Standard Deviation 1.58 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 36 (n=25) | 2.58 milligrams per deciliter (mg/dL) | Standard Deviation 3 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Baseline (n=24) | 0.51 milligrams per deciliter (mg/dL) | Standard Deviation 0.91 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 48 (n=21) | 0.21 milligrams per deciliter (mg/dL) | Standard Deviation 0.27 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 56 (n=24) | 0.41 milligrams per deciliter (mg/dL) | Standard Deviation 0.92 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 68 (n=24) | 0.43 milligrams per deciliter (mg/dL) | Standard Deviation 0.74 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 80 (n=24) | 0.64 milligrams per deciliter (mg/dL) | Standard Deviation 1.91 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 92 (n=23) | 1.86 milligrams per deciliter (mg/dL) | Standard Deviation 7.11 |
| Tocilizumab | C-Reactive Protein (CRP) Level | Week 104 (n=25) | 0.12 milligrams per deciliter (mg/dL) | Standard Deviation 0.16 |
| Tocilizumab | C-Reactive Protein (CRP) Level | FU Visit 1 (n=13) | 0.10 milligrams per deciliter (mg/dL) | Standard Deviation 0.11 |
| Tocilizumab | C-Reactive Protein (CRP) Level | FU Visit 2 (n=24) | 1.46 milligrams per deciliter (mg/dL) | Standard Deviation 5.05 |
Secondary
Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
DAS28 score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), participant's global assessment of disease activity (general health \[GH\]) using visual analog scale (VAS), 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (erythrocyte sedimentation rate \[ESR\] in millimeters per hour \[mm/hr\]) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28 = \[0.56 multiplied by (\*) square root (√) of TJC28\] plus (+) \[0.28\*√SJC28\]+\[0.70\*the natural logarithm (ln) ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and follow-up (FU) Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Baseline (n=26) | 2.76 units on a scale | Standard Deviation 1.19 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 12 (n=24) | 2.23 units on a scale | Standard Deviation 0.86 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 24 (n=25) | 2.43 units on a scale | Standard Deviation 1.01 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 36 (n=25) | 2.04 units on a scale | Standard Deviation 0.85 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 48 (n=21) | 2.32 units on a scale | Standard Deviation 1.23 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 56 (n=24) | 1.82 units on a scale | Standard Deviation 0.55 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 68 (n=23) | 2.21 units on a scale | Standard Deviation 0.84 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 80 (n=24) | 2.06 units on a scale | Standard Deviation 0.64 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 92 (n=24) | 2.23 units on a scale | Standard Deviation 0.96 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 104 (n=25) | 1.92 units on a scale | Standard Deviation 0.93 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | FU Visit 1 (n=13) | 1.70 units on a scale | Standard Deviation 1.02 |
| Tocilizumab | Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | FU Visit 2 (n=24) | 3.21 units on a scale | Standard Deviation 1.35 |
Secondary
ESR Level
ESR is an acute phase reactant and is a measure of inflammation.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | ESR Level | Baseline (n=26) | 9.8 mm/hr | Standard Deviation 10.2 |
| Tocilizumab | ESR Level | Week 12 (n=24) | 4.9 mm/hr | Standard Deviation 3.1 |
| Tocilizumab | ESR Level | Week 24 (n=25) | 8.5 mm/hr | Standard Deviation 7.6 |
| Tocilizumab | ESR Level | Week 36 (n=25) | 4.6 mm/hr | Standard Deviation 3.2 |
| Tocilizumab | ESR Level | Week 48 (n=21) | 5.1 mm/hr | Standard Deviation 4.7 |
| Tocilizumab | ESR Level | Week 56 (n=24) | 4.9 mm/hr | Standard Deviation 5.3 |
| Tocilizumab | ESR Level | Week 68 (n=23) | 6.7 mm/hr | Standard Deviation 7.2 |
| Tocilizumab | ESR Level | Week 80 (n=24) | 6.4 mm/hr | Standard Deviation 9.1 |
| Tocilizumab | ESR Level | Week 92 (n=24) | 7.5 mm/hr | Standard Deviation 9.2 |
| Tocilizumab | ESR Level | Week 104 (n=25) | 5.5 mm/hr | Standard Deviation 6.3 |
| Tocilizumab | ESR Level | FU Visit 1 (n=13) | 4.8 mm/hr | Standard Deviation 5 |
| Tocilizumab | ESR Level | FU Visit 2 (n=24) | 21.9 mm/hr | Standard Deviation 29.7 |
Secondary
Global Evaluation of Disease Activity by the Participant Using VAS Score
Participant's global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as inactive disease (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as disease maximum activity (maximum activity of arthritis). The participant marked the line according to their assessment and the distance from the left edge was measured.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | FU Visit 2 (n=25) | 42.6 mm | Standard Deviation 29.9 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Baseline (n=26) | 35.2 mm | Standard Deviation 25.3 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 12 (n=26) | 36.4 mm | Standard Deviation 26.4 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 24 (n=26) | 38.4 mm | Standard Deviation 27.2 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 36 (n=25) | 31.8 mm | Standard Deviation 25 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 48 (n=23) | 32.8 mm | Standard Deviation 28.8 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 56 (n=25) | 30.6 mm | Standard Deviation 22.7 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 68 (n=24) | 32.4 mm | Standard Deviation 24.6 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 80 (n=24) | 36.1 mm | Standard Deviation 26.2 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 92 (n=25) | 36.2 mm | Standard Deviation 25.5 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | Week 104 (n=25) | 33.4 mm | Standard Deviation 25.2 |
| Tocilizumab | Global Evaluation of Disease Activity by the Participant Using VAS Score | FU Visit 1 (n=15) | 37.1 mm | Standard Deviation 28 |
Secondary
Global Evaluation of Disease Activity by the Physician Using VAS Score
Physician global assessment of disease activity was measured on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as inactive disease (free of symptoms and without symptoms of arthritis) and 100 mm (right end of the line) as disease maximum activity (maximum activity of arthritis). The physician marked the line according to their assessment and the distance from the left edge was measured.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Baseline (n=26) | 20.6 mm | Standard Deviation 18.7 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 12 (n=26) | 11.4 mm | Standard Deviation 14.1 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 24 (n=26) | 13.8 mm | Standard Deviation 14.7 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 36 (n=25) | 13.1 mm | Standard Deviation 10.4 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 48 (n=23) | 9.1 mm | Standard Deviation 11.3 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 56 (n=25) | 13.0 mm | Standard Deviation 13.3 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 68 (n=24) | 11.6 mm | Standard Deviation 11.9 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 80 (n=24) | 11.3 mm | Standard Deviation 11.2 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 92 (n=25) | 13.7 mm | Standard Deviation 11.7 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | Week 104 (n=25) | 10.0 mm | Standard Deviation 9.7 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | FU Visit 1 (n=15) | 11.7 mm | Standard Deviation 11.5 |
| Tocilizumab | Global Evaluation of Disease Activity by the Physician Using VAS Score | FU Visit 2 (n=25) | 15.3 mm | Standard Deviation 18.4 |
Secondary
Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/personal care, ability to stand-up, eating, walking, hygiene, reaching, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents 'no disability' and 3 represents 'very severe, high-dependency disability'.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Baseline (n=26) | 0.68 units on a scale | Standard Deviation 0.61 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 12 (n=26) | 0.49 units on a scale | Standard Deviation 0.43 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 24 (n=26) | 0.49 units on a scale | Standard Deviation 0.38 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 36 (n=25) | 0.49 units on a scale | Standard Deviation 0.45 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 48 (n=23) | 0.48 units on a scale | Standard Deviation 0.49 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 56 (n=24) | 0.53 units on a scale | Standard Deviation 0.6 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 68 (n=24) | 0.52 units on a scale | Standard Deviation 0.47 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 80 (n=24) | 0.53 units on a scale | Standard Deviation 0.48 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 92 (n=23) | 0.43 units on a scale | Standard Deviation 0.44 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | Week 104 (n=24) | 0.48 units on a scale | Standard Deviation 0.5 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | FU Visit 1 (n=15) | 0.56 units on a scale | Standard Deviation 0.42 |
| Tocilizumab | Health Assessment Questionnaire - Disability Index (HAQ-DI) Score | FU Visit 2 (n=23) | 0.63 units on a scale | Standard Deviation 0.59 |
Secondary
Health Assessment Questionnaire (HAQ) Pain VAS Score
The HAQ pain VAS is a measure of pain on a continuous 100 mm scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 mm (severe pain).
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Baseline (n=26) | 31.9 mm | Standard Deviation 22.6 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 12 (n=26) | 30.8 mm | Standard Deviation 24.5 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 24 (n=26) | 37.8 mm | Standard Deviation 26.3 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 36 (n=25) | 30.1 mm | Standard Deviation 23.4 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 48 (n=23) | 32.7 mm | Standard Deviation 29.4 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 56 (n=24) | 31.3 mm | Standard Deviation 24 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 68 (n=24) | 32.9 mm | Standard Deviation 25.1 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 80 (n=24) | 34.4 mm | Standard Deviation 27.2 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 92 (n=23) | 38.2 mm | Standard Deviation 30.3 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | Week 104 (n=24) | 29.0 mm | Standard Deviation 23.9 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | FU Visit 1 (n=15) | 30.9 mm | Standard Deviation 24.8 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Pain VAS Score | FU Visit 2 (n=22) | 43.3 mm | Standard Deviation 32.8 |
Secondary
Participant's Pain Assessment Using VAS Score
Participant's pain assessment was made on a horizontal 0-100 mm VAS, with 0 mm (left end of the line) described as no pain and 100 mm (right end of the line) as unbearable pain. The participant marked the line according to their assessment and the distance from the left edge was measured.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 92 (n=25) | 29.5 mm | Standard Deviation 22.7 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 24 (n=26) | 33.7 mm | Standard Deviation 25.4 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 36 (n=25) | 28.6 mm | Standard Deviation 21.5 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Baseline (n=26) | 31.9 mm | Standard Deviation 21.7 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 12 (n=26) | 29.0 mm | Standard Deviation 25.1 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 48 (n=23) | 27.8 mm | Standard Deviation 25.2 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 56 (n=25) | 27.4 mm | Standard Deviation 23.1 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 68 (n=24) | 27.8 mm | Standard Deviation 23.1 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 80 (n=24) | 31.9 mm | Standard Deviation 24.3 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | Week 104 (n=25) | 28.6 mm | Standard Deviation 22.6 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | FU Visit 1 (n=15) | 28.9 mm | Standard Deviation 25.8 |
| Tocilizumab | Participant's Pain Assessment Using VAS Score | FU Visit 2 (n=25) | 42.6 mm | Standard Deviation 30.1 |
Secondary
Swollen Joint Count (SJC)
An assessment of 28 joints was conducted for swelling. Joints were assessed and classified as swollen/not swollen by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for swelling.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Swollen Joint Count (SJC) | Baseline (n=26) | 1.4 swollen joints | Standard Deviation 2 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 12 (n=24) | 1.0 swollen joints | Standard Deviation 2 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 24 (n=25) | 0.6 swollen joints | Standard Deviation 1.2 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 36 (n=25) | 0.9 swollen joints | Standard Deviation 1 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 48 (n=21) | 1.4 swollen joints | Standard Deviation 2.5 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 56 (n=24) | 0.8 swollen joints | Standard Deviation 1.8 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 68 (n=23) | 0.9 swollen joints | Standard Deviation 1.5 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 80 (n=24) | 0.4 swollen joints | Standard Deviation 0.8 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 92 (n=24) | 0.8 swollen joints | Standard Deviation 1.2 |
| Tocilizumab | Swollen Joint Count (SJC) | Week 104 (n=25) | 0.6 swollen joints | Standard Deviation 1.3 |
| Tocilizumab | Swollen Joint Count (SJC) | FU Visit 1 (n=13) | 0.2 swollen joints | Standard Deviation 0.4 |
| Tocilizumab | Swollen Joint Count (SJC) | FU Visit 2 (n=24) | 1.5 swollen joints | Standard Deviation 2.2 |
Secondary
Tender Joint Count (TJC)
An assessment of 28 joints was conducted for tenderness. Joints were assessed and classified as tender/not tender by pressure and joint manipulation after a physical examination. Artificial joints, arthrodesis or fused joints were not taken into consideration for tenderness.
Time frame: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, and FU Visit 1 (Week 108), FU Visit 2 (Week 116)
Population: ITT population. Here, n=Number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Tender Joint Count (TJC) | Baseline (n=26) | 2.8 tender joints | Standard Deviation 3.6 |
| Tocilizumab | Tender Joint Count (TJC) | Week 12 (n=24) | 1.8 tender joints | Standard Deviation 2.3 |
| Tocilizumab | Tender Joint Count (TJC) | Week 24 (n=25) | 2.0 tender joints | Standard Deviation 3.6 |
| Tocilizumab | Tender Joint Count (TJC) | Week 36 (n=25) | 1.9 tender joints | Standard Deviation 2.5 |
| Tocilizumab | Tender Joint Count (TJC) | Week 48 (n=21) | 2.8 tender joints | Standard Deviation 3.8 |
| Tocilizumab | Tender Joint Count (TJC) | Week 56 (n=24) | 1.1 tender joints | Standard Deviation 1.2 |
| Tocilizumab | Tender Joint Count (TJC) | Week 68 (n=23) | 2.0 tender joints | Standard Deviation 2.6 |
| Tocilizumab | Tender Joint Count (TJC) | Week 80 (n=24) | 1.6 tender joints | Standard Deviation 2 |
| Tocilizumab | Tender Joint Count (TJC) | Week 92 (n=24) | 1.5 tender joints | Standard Deviation 1.7 |
| Tocilizumab | Tender Joint Count (TJC) | Week 104 (n=25) | 1.5 tender joints | Standard Deviation 1.8 |
| Tocilizumab | Tender Joint Count (TJC) | FU Visit 1 (n=13) | 1.8 tender joints | Standard Deviation 3.7 |
| Tocilizumab | Tender Joint Count (TJC) | FU Visit 2 (n=24) | 2.8 tender joints | Standard Deviation 4.7 |