Rheumatoid Arthritis
Conditions
Keywords
Early Rheumatoid Arthritis, Tumor Necrosis Factor Optimization
Brief summary
This study compared the safety and efficacy of combination therapy with adalimumab plus methotrexate (MTX) to that of MTX monotherapy (i.e., placebo plus MTX) in subjects with early rheumatoid arthritis (RA).
Detailed description
This was a 78-week, multicenter, randomized, double-blind, double-treatment period study designed to compare the safety and efficacy of adalimumab and MTX with placebo and MTX in subjects with early RA. Subjects were randomized to receive adalimumab 40 mg every other week (eow) or placebo subcutaneous injections in combination with orally administered MTX for 26 weeks (Period 1). All subjects in all arms received open-label MTX weekly throughout the study (both Period 1 and Period 2). At Weeks 22 and 26, subjects were assessed for achievement of low disease activity, defined as a DAS28 score below 3.2. DAS28 is a measure of RA disease activity calculated using the number of tender and swollen joints (out of a total of 28), C-reactive protein level (CRP, a blood marker of inflammation), and the patient's global assessment of disease activity (indicated by marking a 10 cm line between very good and very bad). Subjects who achieved low disease activity at Week 22 and 26 in the adalimumab arm at the end of Period 1 were randomized to receive MTX monotherapy (placebo and MTX) or combination therapy (adalimumab and MTX) in a 1:1 ratio for the duration of Period 2 (52 weeks, i.e., to Week 78 of the study). Subjects achieving low disease activity at Week 22 and 26 in the placebo arm (MTX monotherapy) at the end of Period 1 continued to receive MTX monotherapy (and placebo injections in a blinded fashion) for the duration of Period 2. Subjects failing to achieve low disease activity at Week 22 and 26 at the end of Period 1 received open-label combination therapy during Period 2 regardless of treatment assignment in Period 1.
Interventions
BIOLOGICALadalimumab
Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
DRUGmethotrexate
Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week.
BIOLOGICALplacebo
Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
Sponsors
Abbott
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
* Subject must be 18 or older and in good health * Subject must meet the definition of early rheumatoid arthritis (RA) defined by the 1987-revised American College of Rheumatology (ACR) classification criteria and had disease duration of less than 1 year from diagnosis * Subject must have a Disease Activity Score (DAS28, based on C-reactive protein) greater than 3.2, at least 6 swollen joints out of the 66 assessed, and at least 8 tender joints out of the 68 assessed * Subject must fulfill at least one of the following three criteria: * Rheumatoid factor positive * Greater than 1 joint erosion * Anti-cyclic citrullinated peptide (CCP) antibody positive.
Exclusion criteria
* Subject has previously received systemic anti-tumor necrosis factor (TNF) therapy * Subject has received any biologic or investigational therapy within 6 weeks prior to Baseline * Subject has been previously treated with more than 2 disease-modifying antirheumatic drugs (DMARDs) or MTX, had been treated with intra-articular or parenteral administration of corticosteroids in preceding 4 weeks, or had undergone joint surgery within the preceding 2 months at joints to be assessed during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4 | Week 78 | The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78 | Week 78 | The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity. |
| Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | Week 78 | The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity. |
| Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78 | Week 78 | For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448. An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. |
| Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78 | Week 78 | Subjects were responders if they had greater than or equal to 20% improvement in tender joint count; greater than or equal to 20% improvement in swollen joint count; and greater than or equal to 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant (C-reactive protein). |
| Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78 | Week 78 | Subjects were responders if they had: greater than or equal to 50% improvement in tender joint count; greater than or equal to 50% improvement in swollen joint count; and greater than or equal to 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant (C-reactive protein). |
| Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78 | Week 78 | Subjects were responders if they had: greater than or equal to 70% improvement in tender joint count; greater than or equal to 70% improvement in swollen joint count; and greater than or equal to 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant (C-reactive protein). |
| Change From Baseline in DAS28 Score at Week 78 | Baseline to Week 78 | The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity. |
| Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78 | Week 78 | The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease. |
| Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1 | Week 78 | The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448. |
| Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78 | Week 78 | The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease. |
| Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78 | Week 78 | The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease. |
| Change From Baseline in CDAI Score at Week 78 | Baseline to Week 78 | The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease. |
| Change From Baseline in SDAI Score at Week 78 | Baseline to Week 78 | The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease. |
| Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78 | Baseline to Week 78 | Synovitis was assessed using high-field magnetic resonance imaging (MRI) of the hand and wrist. Images were read and scored according to the Outcomes Measures in Rheumatology Clinical Trials' Rheumatoid Arthritis MRI Scoring System (OMERACT RAMRIS). Synovitis in the wrist and finger joints in the most affected hand was scored from 0 (normal) to 3 (severe), for a maximum total score of 21. |
| Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78 | Week 78 | In the Health Assessment Questionnaire Disability Index (HAQ-DI), participants rated their ability to perform daily tasks on a scale of 0 (without any difficulty) to 3 (unable to do). A mean score of 0-1 represents mild to moderate functional disability, 1-2 represents moderate to severe, 2-3 severe to very severe disability. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448. |
| Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78 | Week 78 | In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (worst joint damage). American College of Rheumatology 70% (ACR70) response indicates at least 70% improvement in tender and swollen joint counts and at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; HAQ-DI; and C-reactive protein. |
| Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | Week 78 | In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (severe joint damage). The Disease Activity Score (DAS28) ranges from 0.49 to 9.07, with scores less than 2.6 indicating clinical remission. |
| Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78 | Week 78 | The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Mexico, Netherlands, New Zealand, Norway, Poland, Puerto Rico, Slovakia, South Africa, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ADA+MTX Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 | 515 |
| PBO+MTX Methotrexate (MTX) monotherapy plus blinded placebo(PBO) during Period 1 | 517 |
| ADA+MTX/PBO+MTX (Arm 1) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2 | 0 |
| ADA+MTX/ADA+MTX (Arm 2) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2 | 0 |
| ADA+MTX/OL ADA+MTX (Arm 3) Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2 | 0 |
| PBO+MTX/PBO+MTX (Arm 4) Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2 | 0 |
| PBO+MTX/OL ADA+MTX (Arm 5) Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2 | 0 |
| Total | 1,032 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 19 | 15 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Death | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Failed to meet entry criteria | 8 | 7 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Lack of efficacy/Loss of efficacy | 1 | 6 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Lost to Follow-up | 8 | 6 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Noncompliant with study drug | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Randomization error | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Received wrong treatment/incorrect dose | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Study site closure | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Subject moved/relocated | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Subject received new diagnosis | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Suspected tuberculosis/positive test | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Took prohibited medication | 1 | 3 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 7 | 12 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 7 | 3 | 17 | 6 | 20 |
| Period 2 | Lack of efficacy/Loss of efficacy | 0 | 0 | 2 | 1 | 6 | 2 | 6 |
| Period 2 | Lost to Follow-up | 0 | 0 | 2 | 2 | 6 | 3 | 9 |
| Period 2 | Methotrexate intolerance | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 2 | Noncompliant with study drug | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
| Period 2 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Period 2 | Randomization error | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Period 2 | Received wrong treatment/incorrect dose | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 2 | Sponsor decision | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Period 2 | Subject unable to find transportation | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 2 | Took prohibited medication | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 1 | 3 | 11 | 2 | 12 |
Baseline characteristics
| Characteristic | PBO+MTX | ADA+MTX | Total |
|---|---|---|---|
| Age Categorical <=18 years | 0 participants | 0 participants | 0 participants |
| Age Categorical >=65 years | 86 participants | 97 participants | 183 participants |
| Age Categorical Between 18 and 65 years | 431 participants | 418 participants | 849 participants |
| Age Continuous | 50.4 years STANDARD_DEVIATION 13.62 | 50.7 years STANDARD_DEVIATION 14.48 | 50.6 years STANDARD_DEVIATION 14.05 |
| Gender Female | 382 participants | 380 participants | 762 participants |
| Gender Male | 135 participants | 135 participants | 270 participants |
| Region of Enrollment Argentina | 29 participants | 32 participants | 61 participants |
| Region of Enrollment Australia | 8 participants | 5 participants | 13 participants |
| Region of Enrollment Austria | 12 participants | 11 participants | 23 participants |
| Region of Enrollment Belgium | 40 participants | 41 participants | 81 participants |
| Region of Enrollment Canada | 58 participants | 57 participants | 115 participants |
| Region of Enrollment Czech Republic | 19 participants | 22 participants | 41 participants |
| Region of Enrollment France | 8 participants | 4 participants | 12 participants |
| Region of Enrollment Germany | 41 participants | 43 participants | 84 participants |
| Region of Enrollment Hungary | 10 participants | 8 participants | 18 participants |
| Region of Enrollment Mexico | 27 participants | 26 participants | 53 participants |
| Region of Enrollment Netherlands | 3 participants | 0 participants | 3 participants |
| Region of Enrollment New Zealand | 3 participants | 3 participants | 6 participants |
| Region of Enrollment Norway | 5 participants | 4 participants | 9 participants |
| Region of Enrollment Poland | 9 participants | 12 participants | 21 participants |
| Region of Enrollment Slovakia | 3 participants | 6 participants | 9 participants |
| Region of Enrollment South Africa | 32 participants | 31 participants | 63 participants |
| Region of Enrollment Spain | 30 participants | 25 participants | 55 participants |
| Region of Enrollment Sweden | 11 participants | 10 participants | 21 participants |
| Region of Enrollment United Kingdom | 17 participants | 26 participants | 43 participants |
| Region of Enrollment United States | 152 participants | 149 participants | 301 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 102 | 38 / 105 | 106 / 259 | 44 / 112 | 134 / 348 | 149 / 515 | 128 / 517 |
| serious Total, serious adverse events | 11 / 102 | 12 / 105 | 18 / 259 | 9 / 112 | 32 / 348 | 37 / 515 | 32 / 517 |
Outcome results
Primary
Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4
The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
Time frame: Week 78
Population: The analysis was performed on the ITT Population comprised of all subjects who entered Period 2 and received at least 1 dose of study drug (blinded or open-label) during Period 2. Nonresponder imputation was used for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4 | 59 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4 | 73 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4 | 94 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4 | 61 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4 | 129 Participants |
p-value: 0.023Chi-squared
Secondary
Change From Baseline in CDAI Score at Week 78
The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
Time frame: Baseline to Week 78
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Change From Baseline in CDAI Score at Week 78 | -33.30 Scores on a scale | Standard Deviation 12.808 |
| ADA+MTX/ADA+MTX (Arm 2) | Change From Baseline in CDAI Score at Week 78 | -33.29 Scores on a scale | Standard Deviation 12.964 |
| ADA+MTX/OL ADA+MTX (Arm 3) | Change From Baseline in CDAI Score at Week 78 | -29.06 Scores on a scale | Standard Deviation 16.561 |
| PBO+MTX/PBO+MTX (Arm 4) | Change From Baseline in CDAI Score at Week 78 | -27.63 Scores on a scale | Standard Deviation 15.526 |
| PBO+MTX/OL ADA+MTX (Arm 5) | Change From Baseline in CDAI Score at Week 78 | -31.30 Scores on a scale | Standard Deviation 14.769 |
p-value: 0.03ANCOVA
p-value: 0.403ANCOVA
Secondary
Change From Baseline in DAS28 Score at Week 78
The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
Time frame: Baseline to Week 78
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Change From Baseline in DAS28 Score at Week 78 | -3.54 Scores on a scale | Standard Deviation 1.259 |
| ADA+MTX/ADA+MTX (Arm 2) | Change From Baseline in DAS28 Score at Week 78 | -3.71 Scores on a scale | Standard Deviation 1.134 |
| ADA+MTX/OL ADA+MTX (Arm 3) | Change From Baseline in DAS28 Score at Week 78 | -2.70 Scores on a scale | Standard Deviation 1.531 |
| PBO+MTX/PBO+MTX (Arm 4) | Change From Baseline in DAS28 Score at Week 78 | -3.04 Scores on a scale | Standard Deviation 1.513 |
| PBO+MTX/OL ADA+MTX (Arm 5) | Change From Baseline in DAS28 Score at Week 78 | -3.07 Scores on a scale | Standard Deviation 1.486 |
p-value: 0.004ANCOVA
p-value: 0.049ANCOVA
Secondary
Change From Baseline in SDAI Score at Week 78
The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
Time frame: Baseline to Week 78
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Change From Baseline in SDAI Score at Week 78 | -35.61 Scores on a scale | Standard Deviation 13.527 |
| ADA+MTX/ADA+MTX (Arm 2) | Change From Baseline in SDAI Score at Week 78 | -35.16 Scores on a scale | Standard Deviation 13.784 |
| ADA+MTX/OL ADA+MTX (Arm 3) | Change From Baseline in SDAI Score at Week 78 | -31.00 Scores on a scale | Standard Deviation 17.856 |
| PBO+MTX/PBO+MTX (Arm 4) | Change From Baseline in SDAI Score at Week 78 | -29.30 Scores on a scale | Standard Deviation 17.12 |
| PBO+MTX/OL ADA+MTX (Arm 5) | Change From Baseline in SDAI Score at Week 78 | -33.43 Scores on a scale | Standard Deviation 15.852 |
p-value: 0.036ANCOVA
p-value: 0.349ANCOVA
Secondary
Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78
Synovitis was assessed using high-field magnetic resonance imaging (MRI) of the hand and wrist. Images were read and scored according to the Outcomes Measures in Rheumatology Clinical Trials' Rheumatoid Arthritis MRI Scoring System (OMERACT RAMRIS). Synovitis in the wrist and finger joints in the most affected hand was scored from 0 (normal) to 3 (severe), for a maximum total score of 21.
Time frame: Baseline to Week 78
Population: The analysis is based on the Primary Analysis Set, a subset of the ITT Analysis Set that includes subjects who participated in the 78-week HF MRI substudy and whose Baseline HF MRI data were collected on or before the first study drug dose. Observed scores are used in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78 | 2.00 Scores on a scale | Standard Deviation 2.121 |
| ADA+MTX/ADA+MTX (Arm 2) | Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78 | -3.38 Scores on a scale | Standard Deviation 2.562 |
| ADA+MTX/OL ADA+MTX (Arm 3) | Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78 | -3.25 Scores on a scale | Standard Deviation 3.631 |
| PBO+MTX/PBO+MTX (Arm 4) | Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78 | -3.88 Scores on a scale | Standard Deviation 3.351 |
| PBO+MTX/OL ADA+MTX (Arm 5) | Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78 | -4.27 Scores on a scale | Standard Deviation 4.211 |
p-value: 0.037ANCOVA
p-value: <0.001ANCOVA
Secondary
Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78
Subjects were responders if they had greater than or equal to 20% improvement in tender joint count; greater than or equal to 20% improvement in swollen joint count; and greater than or equal to 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant (C-reactive protein).
Time frame: Week 78
Population: ITT Population, nonresponder imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78 | 84 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78 | 89 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78 | 172 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78 | 90 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78 | 257 Participants |
p-value: 0.395Regression, Logistic
p-value: 0.64Regression, Logistic
Secondary
Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78
Subjects were responders if they had: greater than or equal to 50% improvement in tender joint count; greater than or equal to 50% improvement in swollen joint count; and greater than or equal to 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant (C-reactive protein).
Time frame: Week 78
Population: ITT Population, nonresponder imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78 | 72 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78 | 82 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78 | 120 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78 | 78 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78 | 198 Participants |
p-value: 0.159Regression, Logistic
p-value: 0.217Regression, Logistic
Secondary
Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78
Subjects were responders if they had: greater than or equal to 70% improvement in tender joint count; greater than or equal to 70% improvement in swollen joint count; and greater than or equal to 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant (C-reactive protein).
Time frame: Week 78
Population: ITT Population, nonresponder imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78 | 57 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78 | 73 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78 | 78 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78 | 64 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78 | 137 Participants |
p-value: 0.06Regression, Logistic
p-value: 0.043Regression, Logistic
Secondary
Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78
The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78 | 75 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78 | 84 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78 | 109 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78 | 82 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78 | 195 Participants |
p-value: 0.24Regression, Logistic
p-value: 0.271Regression, Logistic
Secondary
Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78
The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78 | 47 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78 | 58 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78 | 39 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78 | 54 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78 | 94 Participants |
p-value: 0.301Regression, Logistic
p-value: 0.188Regression, Logistic
Secondary
Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78
The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
Time frame: Week 78
Population: ITT Population, Nonresponder imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78 | 71 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78 | 80 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78 | 108 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78 | 78 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78 | 185 Participants |
p-value: 0.28Regression, Logistic
p-value: 0.287Regression, Logistic
Secondary
Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78
The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
Time frame: Week 78
Population: ITT Population, nonresponder imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 57 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 77 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 71 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 66 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 138 Participants |
p-value: 0.026Regression, Logistic
p-value: 0.009Regression, Logistic
Secondary
Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1
The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1 | 59 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1 | 73 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1 | 94 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1 | 61 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1 | 129 Participants |
p-value: 0.082Regression, Logistic
Secondary
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78
For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448. An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
Time frame: Week 78
Population: ITT Population, nonresponder imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78 | 70 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78 | 84 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78 | 182 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78 | 77 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78 | 220 Participants |
p-value: 0.06Regression, Logistic
p-value: 0.063Regression, Logistic
Secondary
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78
In the Health Assessment Questionnaire Disability Index (HAQ-DI), participants rated their ability to perform daily tasks on a scale of 0 (without any difficulty) to 3 (unable to do). A mean score of 0-1 represents mild to moderate functional disability, 1-2 represents moderate to severe, 2-3 severe to very severe disability. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78 | 49 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78 | 59 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78 | 65 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78 | 53 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78 | 84 Participants |
p-value: 0.192Regression, Logistic
p-value: 0.241Regression, Logistic
Secondary
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78
In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (severe joint damage). The Disease Activity Score (DAS28) ranges from 0.49 to 9.07, with scores less than 2.6 indicating clinical remission.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 39 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 53 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 38 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 43 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78 | 63 Participants |
p-value: 0.074Regression, Logistic
p-value: 0.077Regression, Logistic
Secondary
Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78
In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (worst joint damage). American College of Rheumatology 70% (ACR70) response indicates at least 70% improvement in tender and swollen joint counts and at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; HAQ-DI; and C-reactive protein.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78 | 37 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78 | 56 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78 | 40 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78 | 43 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78 | 67 Participants |
p-value: 0.028Regression, Logistic
p-value: 0.014Regression, Logistic
Secondary
Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78
The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78 | 73 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78 | 79 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78 | 106 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78 | 76 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78 | 192 Participants |
p-value: 0.23Regression, Logistic
p-value: 0.55Regression, Logistic
Secondary
Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78
The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
Time frame: Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ADA+MTX/PBO+MTX (Arm 1) | Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78 | 45 Participants |
| ADA+MTX/ADA+MTX (Arm 2) | Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78 | 55 Participants |
| ADA+MTX/OL ADA+MTX (Arm 3) | Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78 | 39 Participants |
| PBO+MTX/PBO+MTX (Arm 4) | Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78 | 51 Participants |
| PBO+MTX/OL ADA+MTX (Arm 5) | Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78 | 92 Participants |
p-value: 0.314Regression, Logistic
p-value: 0.235Regression, Logistic