Rheumatoid Arthritis
Conditions
Brief summary
This randomized, double-blind, parallel group study will assess the safety, disease remission, and prevention of structural joint damage in patients with early moderate to severe rheumatoid arthritis treated with tocilizumab as monotherapy or in combination with methotrexate, versus methotrexate alone. Patients will be randomized to receive either (A) tocilizumab (8 mg/kg iv every 4 weeks) plus placebo, (B) tocilizumab (8 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), (C) tocilizumab (4 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), or (D) placebo plus methotrexate (7.5-20 mg po weekly). Patients in groups C and D who have not achieved low disease activity at week 52 can receive tocilizumab 8 mg/kg iv every 4 weeks. Anticipated time on study treatment is 104 weeks.
Interventions
DRUGTocilizumab
Tocilizumab was supplied in vials.
Placebo to tocilizumab was supplied in vials.
DRUGMethotrexate
Initially, patients received methotrexate 7.5 mg (3, 2.5 mg tablets) orally once a week. If a patient had swollen or tender joints, the dose was increased to 15 mg and 20 mg weekly, at the Week 4 and Week 8 visits, respectively.
Patients received placebo to methotrexate orally once a week.
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
* Adult patients ≥ 18 years of age. * Rheumatoid arthritis of ≤ 2 years duration. * Disease Activity Score 28 (DAS28) \> 3.2. * Swollen joint count (SJC) ≥ 4 of 66 joints, tender joint count (TJC) ≥ 6 of 68 joints. * Rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) positive (if RF and anti-CCP negative \> 1 erosion required at screening). * Erythrocyte sedimentation rate (ESR) ≥ 28 mm/h or C-reactive protein (CRP) ≥ 10 mg/L at screening.
Exclusion criteria
* Previous treatment with tocilizumab. * Previous treatment with methotrexate or biologic agent. * Rheumatic autoimmune disease other than rheumatoid arthritis (RA). * History of or current inflammatory joint disease other than RA. * Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in RA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 | Week 24 | A participant has a DAS28 remission response if their DAS28 \< 2.6. The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Baseline to Weeks 24 and 52 | Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line no disease activity \[symptom-free and no arthritis symptoms\] and the extreme right end maximum disease activity; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line no pain and the extreme right end unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing. |
| Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 | Baseline to Week 52 | The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint, including subluxation, is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement. |
| Change From Baseline in Modified Sharp Erosion Score at Week 52 | Baseline to Week 52 | — |
| Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52 | Week 52 | — |
| Percentage of Participants With a Major Clinical Response at Week 52 | Baseline to Week 52 | A major clinical response is defined as an ACR70 response that is maintained for 6 consecutive months (24 weeks) for any 24-week period between Week 2 and Week 52. |
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Baseline to Weeks 24 and 52 | The Stanford HAQ-DI is a patient completed questionnaire specific for rheumatoid arthritis. The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. |
| Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Baseline to Weeks 24 and 52 | The SF-36 Health Survey (Version 2) is a standardized questionnaire consisting of 36 questions that measures patient-reported symptoms on 8 dimensions; it is used to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL. |
| Change From Baseline in Sharp Joint Space Narrowing Score at Week 52 | Baseline to Week 52 | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, China, Colombia, Denmark, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Mexico, New Zealand, North Macedonia, Panama, Peru, Philippines, Poland, Portugal, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Five of 1162 randomized patients (2 placebo to tocilizumab + methotrexate, 2 tocilizumab 4 mg/kg + methotrexate, 1 tocilizumab 8 mg/kg + methotrexate) did not receive any study treatment and were excluded from all analysis populations.
Participants by arm
| Arm | Count |
|---|---|
| Placebo to Tocilizumab + Methotrexate Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks. | 287 |
| Tocilizumab 4 mg/kg + Methotrexate Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks. | 288 |
| Tocilizumab 8 mg/kg + Methotrexate Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks. | 290 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks. | 292 |
| Total | 1,157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 25 | 47 | 31 |
| Overall Study | Death | 2 | 4 | 2 | 1 |
| Overall Study | Failure to Return | 5 | 4 | 3 | 6 |
| Overall Study | Insufficient Therapeutic Response | 21 | 7 | 2 | 9 |
| Overall Study | Other Protocol Violation | 2 | 0 | 1 | 0 |
| Overall Study | Reason not Specified | 1 | 1 | 2 | 1 |
| Overall Study | Refused Treatment | 13 | 13 | 5 | 8 |
| Overall Study | Violation of Selection Criteria at Entry | 3 | 5 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo to Tocilizumab + Methotrexate | Tocilizumab 4 mg/kg + Methotrexate | Tocilizumab 8 mg/kg + Methotrexate | Tocilizumab 8 mg/kg + Placebo to Methotrexate | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 13.1 | 51.2 years STANDARD_DEVIATION 13.84 | 49.5 years STANDARD_DEVIATION 13.7 | 49.9 years STANDARD_DEVIATION 13.22 | 50.1 years STANDARD_DEVIATION 13.47 |
| Sex: Female, Male Female | 229 Participants | 228 Participants | 228 Participants | 219 Participants | 904 Participants |
| Sex: Female, Male Male | 58 Participants | 60 Participants | 62 Participants | 73 Participants | 253 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 177 / 282 | 182 / 289 | 201 / 290 | 163 / 292 |
| serious Total, serious adverse events | 24 / 282 | 29 / 289 | 31 / 290 | 25 / 292 |
Outcome results
Primary
Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24
A participant has a DAS28 remission response if their DAS28 \< 2.6. The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time frame: Week 24
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 | 15.0 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 | 31.9 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 | 44.8 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24 | 38.7 Percentage of participants |
Comparison: The null hypothesis is that there is no difference in the DAS28 remission response at Week 24 between the placebo to tocilizumab + methotrexate and the tocilizumab 8 mg/kg + methotrexate treatment groups.p-value: <0.000195% CI: [3.19, 7.14]Regression, Logistic
Comparison: The null hypothesis is that there is no difference in the DAS28 remission response at Week 24 between the placebo to tocilizumab + methotrexate and the tocilizumab 8 mg/kg + placebo to methotrexate treatment groups.p-value: <0.000195% CI: [2.47, 5.55]Regression, Logistic
Comparison: The null hypothesis is that there is no difference in the DAS28 remission response at Week 24 between the placebo to tocilizumab + methotrexate and the tocilizumab 4 mg/kg + methotrexate treatment groups.p-value: <0.000195% CI: [1.8, 4.11]Regression, Logistic
Secondary
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52
The Stanford HAQ-DI is a patient completed questionnaire specific for rheumatoid arthritis. The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Time frame: Baseline to Weeks 24 and 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 24 (n=246, 255, 250, 265) | -0.71 Units on a scale | Standard Deviation 0.718 |
| Placebo to Tocilizumab + Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 52 (n=214, 227, 228, 230) | -0.76 Units on a scale | Standard Deviation 0.8 |
| Tocilizumab 4 mg/kg + Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 52 (n=214, 227, 228, 230) | -1.00 Units on a scale | Standard Deviation 0.795 |
| Tocilizumab 4 mg/kg + Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 24 (n=246, 255, 250, 265) | -0.92 Units on a scale | Standard Deviation 0.736 |
| Tocilizumab 8 mg/kg + Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 24 (n=246, 255, 250, 265) | -0.91 Units on a scale | Standard Deviation 0.695 |
| Tocilizumab 8 mg/kg + Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 52 (n=214, 227, 228, 230) | -0.97 Units on a scale | Standard Deviation 0.7 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 24 (n=246, 255, 250, 265) | -0.82 Units on a scale | Standard Deviation 0.739 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52 | Week 52 (n=214, 227, 228, 230) | -0.87 Units on a scale | Standard Deviation 0.776 |
Secondary
Change From Baseline in Modified Sharp Erosion Score at Week 52
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Change From Baseline in Modified Sharp Erosion Score at Week 52 | 0.63 Units on a scale | Standard Deviation 2.556 |
| Tocilizumab 4 mg/kg + Methotrexate | Change From Baseline in Modified Sharp Erosion Score at Week 52 | 0.25 Units on a scale | Standard Deviation 1.686 |
| Tocilizumab 8 mg/kg + Methotrexate | Change From Baseline in Modified Sharp Erosion Score at Week 52 | 0.05 Units on a scale | Standard Deviation 1.736 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Change From Baseline in Modified Sharp Erosion Score at Week 52 | 0.15 Units on a scale | Standard Deviation 1.544 |
Secondary
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint, including subluxation, is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 | 1.14 Units on a scale | Standard Deviation 4.297 |
| Tocilizumab 4 mg/kg + Methotrexate | Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 | 0.42 Units on a scale | Standard Deviation 2.929 |
| Tocilizumab 8 mg/kg + Methotrexate | Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 | 0.08 Units on a scale | Standard Deviation 2.09 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 | 0.26 Units on a scale | Standard Deviation 1.876 |
Secondary
Change From Baseline in Sharp Joint Space Narrowing Score at Week 52
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Change From Baseline in Sharp Joint Space Narrowing Score at Week 52 | 0.51 Units on a scale | Standard Deviation 2.362 |
| Tocilizumab 4 mg/kg + Methotrexate | Change From Baseline in Sharp Joint Space Narrowing Score at Week 52 | 0.17 Units on a scale | Standard Deviation 1.645 |
| Tocilizumab 8 mg/kg + Methotrexate | Change From Baseline in Sharp Joint Space Narrowing Score at Week 52 | 0.03 Units on a scale | Standard Deviation 0.751 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Change From Baseline in Sharp Joint Space Narrowing Score at Week 52 | 0.11 Units on a scale | Standard Deviation 1.046 |
Secondary
Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52
The SF-36 Health Survey (Version 2) is a standardized questionnaire consisting of 36 questions that measures patient-reported symptoms on 8 dimensions; it is used to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL.
Time frame: Baseline to Weeks 24 and 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 24 (n=237, 247, 246, 255) | 9.35 Units on a scale | Standard Deviation 9.763 |
| Placebo to Tocilizumab + Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 52 (n=204, 225, 221, 224) | 10.72 Units on a scale | Standard Deviation 10.389 |
| Tocilizumab 4 mg/kg + Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 52 (n=204, 225, 221, 224) | 12.27 Units on a scale | Standard Deviation 10.509 |
| Tocilizumab 4 mg/kg + Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 24 (n=237, 247, 246, 255) | 11.33 Units on a scale | Standard Deviation 9.282 |
| Tocilizumab 8 mg/kg + Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 24 (n=237, 247, 246, 255) | 12.13 Units on a scale | Standard Deviation 9.263 |
| Tocilizumab 8 mg/kg + Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 52 (n=204, 225, 221, 224) | 13.52 Units on a scale | Standard Deviation 9.848 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 24 (n=237, 247, 246, 255) | 10.75 Units on a scale | Standard Deviation 10.055 |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52 | Week 52 (n=204, 225, 221, 224) | 11.73 Units on a scale | Standard Deviation 10.691 |
Secondary
Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52
Time frame: Week 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52 | 19.5 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52 | 34.0 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52 | 49.0 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52 | 39.4 Percentage of participants |
Secondary
Percentage of Participants With a Major Clinical Response at Week 52
A major clinical response is defined as an ACR70 response that is maintained for 6 consecutive months (24 weeks) for any 24-week period between Week 2 and Week 52.
Time frame: Baseline to Week 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Percentage of Participants With a Major Clinical Response at Week 52 | 16 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Participants With a Major Clinical Response at Week 52 | 22 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Participants With a Major Clinical Response at Week 52 | 31 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Participants With a Major Clinical Response at Week 52 | 22 Percentage of participants |
Secondary
Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52
Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line no disease activity \[symptom-free and no arthritis symptoms\] and the extreme right end maximum disease activity; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line no pain and the extreme right end unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing.
Time frame: Baseline to Weeks 24 and 52
Population: Intent-to-treat population: All randomized participants who received at least 1 tocilizumab/placebo infusion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo to Tocilizumab + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 20 | 65.2 Percentage of participants |
| Placebo to Tocilizumab + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 50 | 43.2 Percentage of participants |
| Placebo to Tocilizumab + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 70 | 25.4 Percentage of participants |
| Placebo to Tocilizumab + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 20 | 57.1 Percentage of participants |
| Placebo to Tocilizumab + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 50 | 40.8 Percentage of participants |
| Placebo to Tocilizumab + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 70 | 28.9 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 70 | 37.2 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 20 | 62.8 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 20 | 73.6 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 70 | 34.7 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 50 | 47.9 Percentage of participants |
| Tocilizumab 4 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 50 | 52.4 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 50 | 56.9 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 70 | 38.6 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 20 | 67.2 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 70 | 43.1 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 50 | 55.9 Percentage of participants |
| Tocilizumab 8 mg/kg + Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 20 | 74.5 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 50 | 49.3 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 70 | 36.0 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 50 | 47.6 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 52: ACR 20 | 63.0 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 20 | 70.2 Percentage of participants |
| Tocilizumab 8 mg/kg + Placebo to Methotrexate | Percentage of Patients With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52 | Week 24: ACR 70 | 30.1 Percentage of participants |