Rheumatoid Arthritis
Conditions
Keywords
Early Rheumatoid Arthritis, Joint Structure, Magnetic Resonance Imaging, Janus Kinase (JAK) Inhibitor, Tasocitinib, Tofacitinib
Brief summary
Evaluation of efficacy and safety of tofacitinib (CP-690,550) for the treatment of early rheumatoid arthritis in adult patients with moderate to severe disease who are methotrexate naïve. The efficacy will be evaluated by exploring the effects on joint structure assessed by magnetic resonance imaging, x-rays and by standard clinical assessment.
Interventions
DRUGTasocitinib plus Methotrexate
Tofacitinib (CP 690,550) 10 mg BID, tablets + methotrexate (MTX) 10 mg/wk to 20 mg/wk, titrated over 2 months
DRUGTofacitinib plus placebo methotrexate
Tofacitinib (CP-90,550) 10 mg BID, tablets. Placebo to match methotrexate (MTX) capsules titrated as in Treatment Arm 1.
DRUGPlacebo tofacitinib plus Methotrexate
Methotrexate (MTX) 10 mg/wk to 20 mg/wk, capsules, titrated over 2 months. Placebo in tablets to match tofacitinib
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients with moderate to severe early rheumatoid arthritis (\< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive.
Exclusion criteria
* Pregnant or lactating patients; * Patients with renal or hepatic impairment or other severe or progressing disease; * Patients with contraindication to magnetic resonance imaging with gadolinium contrast.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis | Month 3 | Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement. |
| Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema | Month 6 | Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Months 1, 3, 6, and 12 | Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity. |
| Modified Total Sharp Score (mTSS) at Months 6 and 12 | Months 6 and 12 | Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) plus (+) erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. |
| Change From Baseline to Months 6 and 12 in mTSS | Months 6 and 12 | Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) + erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. |
| Joint Space Narrowing (JSN) Scores at Months 6 and 12 | Months 6 and 12 | JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. |
| Change From Baseline to Months 6 and 12 in JSN Scores | Months 6 and 12 | JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. |
| Erosion Scores at Months 6 and 12 | Months 6 and 12 | Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. |
| Change From Baseline to Months 6 and 12 in Erosion Score | Months 6 and 12 | Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. |
| Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Months 1, 2, 3, 6, 9, and 12 | ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Participant's Assessment of Pain; Participant's Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). |
| Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Months 1, 2, 3, 6, 9, and 12 | ACR50 response: ≥ 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of disease activity, 3) Paricipant's Assessment of Pain, 4) Participant's assessment of functional disability via a HAQ, and 5) CRP at each visit. |
| Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Months 1, 2, 3, 6, 9, and 12 | ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of Disease Activity, 3) Participant's Assessment of Pain, 4) Participant's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit. |
| Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Months 1, 6, and 12 | Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement. |
| Change From Baseline in DAS28-3 (CRP) | Months 1, 2, 3, 6, 9, and 12 | DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. |
| Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Baseline and Months 1, 2, 3, 6, 9, and 12 | DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) ≤3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) \<2.6 = remission. |
| Change From Baseline in DAS28-4 (ESR) | Months 1, 2, 3, 6, 9, and 12 | DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. |
| Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Months 1, 2, 3, 6, 9, and 12 | DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL). |
| Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Months 1, 2, 3, 6, 9, and 12 | DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity. |
| Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Months 1, 2, 3, 6, 9, and 12 | DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) \<2.6 implied remission. |
| Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Months 1, 2, 3, 6, 9, and 12 | DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL). |
| Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Months 1, 2, 3, 6, 9, and 12 | DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity. |
| Percentage of Participants With DAS28-4 (ESR) <2.6 | Months 1, 2, 3, 6, 9, and 12 | DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) \<2.6 implied remission. |
| Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Baseline and Months 1, 2, 3, 6, 9, and 12 | DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (≤)3.2 implied low disease activity and greater than (\>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (\<)2.6 = remission. |
| Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Months 1, 3, and 12 | Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0â€3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1â€33% of bone edematous; 2: 34â€66% of bone edematous; 3: 67â€100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. |
Countries
Argentina, Chile, Croatia, Czechia, Hungary, Mexico, Poland, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tofacitinib (CP-690,550) Plus MTX Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. | 36 |
| Tofacitinib (CP-690,550) Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. | 36 |
| Methotrexate Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. | 37 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 | 5 |
| Overall Study | Lack of Efficacy | 0 | 0 | 6 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 2 |
| Overall Study | Reason not specified | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 3 |
Baseline characteristics
| Characteristic | Tofacitinib (CP-690,550) Plus MTX | Tofacitinib (CP-690,550) | Methotrexate | Total |
|---|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 12.3 | 50.8 years STANDARD_DEVIATION 12.8 | 47.8 years STANDARD_DEVIATION 11.6 | 48.8 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 31 Participants | 30 Participants | 29 Participants | 90 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 8 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 36 | 31 / 36 | 29 / 37 |
| serious Total, serious adverse events | 2 / 36 | 1 / 36 | 2 / 37 |
Outcome results
Primary
Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis
Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: Month 3
Population: Evaluable Set: all randomized participants who received at least 1 dose of the randomized investigational drug and for whom a variable is nonmissing at both baseline and the specified timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis | -0.80 score on a scale | Standard Error 0.41 |
| Tofacitinib (CP-690,550) | Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis | -0.69 score on a scale | Standard Error 0.4 |
| Methotrexate | Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis | -0.17 score on a scale | Standard Error 0.4 |
p-value: 0.269690% CI: [-1.58, 0.31]mixed model repeated measures analysis
p-value: 0.356190% CI: [-1.46, 0.41]mixed model repeated measures analysis
Primary
Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema
Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.
Time frame: Month 6
Population: Evaluable Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema | -1.26 score on a scale | Standard Error 0.41 |
| Tofacitinib (CP-690,550) | Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema | -1.45 score on a scale | Standard Error 0.42 |
| Methotrexate | Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema | 0.29 score on a scale | Standard Error 0.42 |
p-value: 0.008990% CI: [-2.52, -0.58]mixed model repeated measures analysis
p-value: 0.003890% CI: [-2.72, -0.76]mixed model repeated measures analysis
Secondary
Change From Baseline in DAS28-3 (CRP)
DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-3 (CRP) | Month 1 (n=33,35,37) | -1.61 scores on a scale | Standard Error 0.19 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-3 (CRP) | Month 2 (n=33,33,32) | -2.32 scores on a scale | Standard Error 0.19 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-3 (CRP) | Month 3 (n=33,33,31) | -2.25 scores on a scale | Standard Error 0.19 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-3 (CRP) | Month 6 (n=31,29,29) | -2.54 scores on a scale | Standard Error 0.19 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-3 (CRP) | Month 9 (n=30,28,24) | -2.92 scores on a scale | Standard Error 0.2 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-3 (CRP) | Month 12 (n=27,26,20) | -2.78 scores on a scale | Standard Error 0.2 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-3 (CRP) | Month 12 (n=27,26,20) | -2.61 scores on a scale | Standard Error 0.2 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-3 (CRP) | Month 1 (n=33,35,37) | -1.40 scores on a scale | Standard Error 0.18 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-3 (CRP) | Month 6 (n=31,29,29) | -2.55 scores on a scale | Standard Error 0.2 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-3 (CRP) | Month 9 (n=30,28,24) | -2.43 scores on a scale | Standard Error 0.2 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-3 (CRP) | Month 2 (n=33,33,32) | -1.88 scores on a scale | Standard Error 0.19 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-3 (CRP) | Month 3 (n=33,33,31) | -1.96 scores on a scale | Standard Error 0.19 |
| Methotrexate | Change From Baseline in DAS28-3 (CRP) | Month 2 (n=33,33,32) | -1.24 scores on a scale | Standard Error 0.19 |
| Methotrexate | Change From Baseline in DAS28-3 (CRP) | Month 3 (n=33,33,31) | -1.57 scores on a scale | Standard Error 0.19 |
| Methotrexate | Change From Baseline in DAS28-3 (CRP) | Month 12 (n=27,26,20) | -1.77 scores on a scale | Standard Error 0.22 |
| Methotrexate | Change From Baseline in DAS28-3 (CRP) | Month 6 (n=31,29,29) | -1.52 scores on a scale | Standard Error 0.19 |
| Methotrexate | Change From Baseline in DAS28-3 (CRP) | Month 1 (n=33,35,37) | -0.73 scores on a scale | Standard Error 0.18 |
| Methotrexate | Change From Baseline in DAS28-3 (CRP) | Month 9 (n=30,28,24) | -1.76 scores on a scale | Standard Error 0.21 |
Comparison: Month 1p-value: 0.00190% CI: [-1.31, -0.45]mixed model repeated measures analysis
Comparison: Month 1p-value: 0.010290% CI: [-1.1, -0.24]mixed model repeated measures analysis
Comparison: Month 2p-value: <0.000190% CI: [-1.52, -0.64]mixed model repeated measures analysis
Comparison: Month 2p-value: 0.017590% CI: [-1.08, -0.2]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.012590% CI: [-1.13, -0.23]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.145790% CI: [-0.84, 0.05]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.000390% CI: [-1.48, -0.57]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.000290% CI: [-1.49, -0.58]mixed model repeated measures analysis
Comparison: Month 9p-value: <0.000190% CI: [-1.63, -0.69]mixed model repeated measures analysis
Comparison: Month 9p-value: 0.019690% CI: [-1.14, -0.2]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.000790% CI: [-1.5, -0.52]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.004990% CI: [-1.32, -0.35]mixed model repeated measures analysis
Secondary
Change From Baseline in DAS28-4 (ESR)
DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-4 (ESR) | Month 1 (n=34,35,37) | -1.77 scores on a scale | Standard Error 0.21 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-4 (ESR) | Month 2 (n=32,33,31) | -2.59 scores on a scale | Standard Error 0.22 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-4 (ESR) | Month 3 (n=33,33,31) | -2.69 scores on a scale | Standard Error 0.21 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-4 (ESR) | Month 6 (n=30,29,28) | -3.02 scores on a scale | Standard Error 0.22 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-4 (ESR) | Month 9 (n=30,28,24) | -3.29 scores on a scale | Standard Error 0.22 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline in DAS28-4 (ESR) | Month 12 (n=27,26,20) | -3.31 scores on a scale | Standard Error 0.22 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-4 (ESR) | Month 12 (n=27,26,20) | -2.84 scores on a scale | Standard Error 0.22 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-4 (ESR) | Month 1 (n=34,35,37) | -1.57 scores on a scale | Standard Error 0.21 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-4 (ESR) | Month 6 (n=30,29,28) | -2.81 scores on a scale | Standard Error 0.22 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-4 (ESR) | Month 9 (n=30,28,24) | -2.72 scores on a scale | Standard Error 0.22 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-4 (ESR) | Month 2 (n=32,33,31) | -2.08 scores on a scale | Standard Error 0.21 |
| Tofacitinib (CP-690,550) | Change From Baseline in DAS28-4 (ESR) | Month 3 (n=33,33,31) | -2.35 scores on a scale | Standard Error 0.21 |
| Methotrexate | Change From Baseline in DAS28-4 (ESR) | Month 2 (n=32,33,31) | -1.41 scores on a scale | Standard Error 0.21 |
| Methotrexate | Change From Baseline in DAS28-4 (ESR) | Month 3 (n=33,33,31) | -1.80 scores on a scale | Standard Error 0.21 |
| Methotrexate | Change From Baseline in DAS28-4 (ESR) | Month 12 (n=27,26,20) | -2.18 scores on a scale | Standard Error 0.24 |
| Methotrexate | Change From Baseline in DAS28-4 (ESR) | Month 6 (n=30,29,28) | -1.73 scores on a scale | Standard Error 0.22 |
| Methotrexate | Change From Baseline in DAS28-4 (ESR) | Month 1 (n=34,35,37) | -0.94 scores on a scale | Standard Error 0.2 |
| Methotrexate | Change From Baseline in DAS28-4 (ESR) | Month 9 (n=30,28,24) | -2.14 scores on a scale | Standard Error 0.23 |
Comparison: Month 6p-value: <0.000190% CI: [-1.81, -0.78]mixed model repeated measures analysis
Comparison: Month 1p-value: 0.004690% CI: [-1.32, -0.35]mixed model repeated measures analysis
Comparison: Month 1p-value: 0.030390% CI: [-1.11, -0.15]mixed model repeated measures analysis
Comparison: Month 2p-value: 0.000190% CI: [-1.69, -0.68]mixed model repeated measures analysis
Comparison: Month 2p-value: 0.025590% CI: [-1.17, -0.18]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.003590% CI: [-1.39, -0.39]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.068390% CI: [-1.05, -0.05]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.000690% CI: [-1.59, -0.56]mixed model repeated measures analysis
Comparison: Month 9p-value: 0.000490% CI: [-1.67, -0.62]mixed model repeated measures analysis
Comparison: Month 9p-value: 0.070690% CI: [-1.1, -0.05]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.000890% CI: [-1.67, -0.58]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.046690% CI: [-1.21, -0.12]mixed model repeated measures analysis
Secondary
Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions
Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity.
Time frame: Months 1, 3, 6, and 12
Population: Evaluable Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 6 (n=33,29,28) | -0.06 score on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 12 (n=29,26,21) | -0.11 score on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 1 (n=28,31,35) | -0.12 score on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 3 (n=30,32,31) | -0.12 score on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 6 (n=33,29,28) | -0.02 score on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 3 (n=30,32,31) | 0.36 score on a scale | Standard Error 0.24 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 12 (n=29,26,21) | -0.08 score on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 1 (n=28,31,35) | 0.27 score on a scale | Standard Error 0.25 |
| Methotrexate | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 12 (n=29,26,21) | 1.18 score on a scale | Standard Error 0.26 |
| Methotrexate | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 1 (n=28,31,35) | 0.27 score on a scale | Standard Error 0.24 |
| Methotrexate | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 3 (n=30,32,31) | 0.44 score on a scale | Standard Error 0.25 |
| Methotrexate | Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions | Month 6 (n=33,29,28) | 0.65 score on a scale | Standard Error 0.25 |
Comparison: Month 1p-value: 0.268990% CI: [-0.96, 0.19]mixed model repeated measures analysis
Comparison: Month 1p-value: 0.993590% CI: [-0.58, 0.57]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.108690% CI: [-1.15, 0.01]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.809290% CI: [-0.66, 0.49]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.046390% CI: [-1.29, -0.12]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.062490% CI: [-1.25, -0.08]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.000590% CI: [-1.9, -0.69]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.000890% CI: [-1.87, -0.65]mixed model repeated measures analysis
Secondary
Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP
Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0â€3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1â€33% of bone edematous; 2: 34â€66% of bone edematous; 3: 67â€100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.
Time frame: Months 1, 3, and 12
Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 3 (n=30,32,31) | -0.77 score on a scale | Standard Error 0.42 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 1 (n=28,31,35) | -0.29 score on a scale | Standard Error 0.43 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 12 (n=29,26,21) | -1.52 score on a scale | Standard Error 0.42 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 3 (n=30,32,31) | -0.86 score on a scale | Standard Error 0.41 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 1 (n=28,31,35) | 0.19 score on a scale | Standard Error 0.41 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 12 (n=29,26,21) | -1.70 score on a scale | Standard Error 0.43 |
| Methotrexate | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 1 (n=28,31,35) | 0.11 score on a scale | Standard Error 0.39 |
| Methotrexate | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 12 (n=29,26,21) | 0.59 score on a scale | Standard Error 0.46 |
| Methotrexate | Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP | Month 3 (n=30,32,31) | 0.47 score on a scale | Standard Error 0.41 |
Comparison: Month 1p-value: 0.48990% CI: [-1.36, 0.56]mixed model repeated measures analysis
Comparison: Month 1p-value: 0.881790% CI: [-0.85, 1.02]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.035190% CI: [-2.21, -0.27]mixed model repeated measures analysis
Comparison: Month 3p-value: 0.023190% CI: [-2.28, -0.37]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.000890% CI: [-3.13, -1.08]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.000390% CI: [-3.32, -1.25]mixed model repeated measures analysis
Secondary
Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis
Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: Months 1, 6, and 12
Population: Evaluable Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 6 (n=33,29,28) | -1.22 score on a scale | Standard Error 0.4 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 1 (n=28,31,35) | -0.42 score on a scale | Standard Error 0.42 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 12 (n=29,26,21) | -2.26 score on a scale | Standard Error 0.41 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 6 (n=33,29,28) | -1.29 score on a scale | Standard Error 0.41 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 1 (n=28,31,35) | -0.34 score on a scale | Standard Error 0.4 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 12 (n=29,26,21) | -1.16 score on a scale | Standard Error 0.43 |
| Methotrexate | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 1 (n=28,31,35) | -0.17 score on a scale | Standard Error 0.38 |
| Methotrexate | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 12 (n=29,26,21) | -0.66 score on a scale | Standard Error 0.46 |
| Methotrexate | Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis | Month 6 (n=33,29,28) | -0.28 score on a scale | Standard Error 0.42 |
Comparison: Month 6p-value: 0.103890% CI: [-1.89, 0.01]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.086890% CI: [-1.98, -0.04]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.010390% CI: [-2.62, -0.58]mixed model repeated measures analysis
Comparison: Month 1p-value: 0.657690% CI: [-1.19, 0.69]mixed model repeated measures analysis
Comparison: Month 1p-value: 0.756590% CI: [-1.09, 0.74]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.43590% CI: [-1.53, 0.55]mixed model repeated measures analysis
Secondary
Change From Baseline to Months 6 and 12 in Erosion Score
Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time frame: Months 6 and 12
Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 6 and 12 in Erosion Score | Month 6 (n=29,27,28) | 0.16 scores on a scale | Standard Error 0.24 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 6 and 12 in Erosion Score | Month 12 (n=26,25,22) | 0.42 scores on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 6 and 12 in Erosion Score | Month 6 (n=29,27,28) | -0.10 scores on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 6 and 12 in Erosion Score | Month 12 (n=26,25,22) | -0.05 scores on a scale | Standard Error 0.26 |
| Methotrexate | Change From Baseline to Months 6 and 12 in Erosion Score | Month 6 (n=29,27,28) | 0.58 scores on a scale | Standard Error 0.25 |
| Methotrexate | Change From Baseline to Months 6 and 12 in Erosion Score | Month 12 (n=26,25,22) | 0.65 scores on a scale | Standard Error 0.27 |
Comparison: Month 6p-value: 0.235190% CI: [-1, 0.16]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.063190% CI: [-1.27, -0.08]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.536990% CI: [-0.83, 0.38]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.06290% CI: [-1.31, -0.08]mixed model repeated measures analysis
Secondary
Change From Baseline to Months 6 and 12 in JSN Scores
JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time frame: Months 6 and 12
Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 6 and 12 in JSN Scores | Month 6 (n=29,27,28) | 0.29 scores on a scale | Standard Error 0.34 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 6 and 12 in JSN Scores | Month 12 (n=26,25,22) | 0.43 scores on a scale | Standard Error 0.35 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 6 and 12 in JSN Scores | Month 6 (n=29,27,28) | -0.06 scores on a scale | Standard Error 0.35 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 6 and 12 in JSN Scores | Month 12 (n=26,25,22) | -0.12 scores on a scale | Standard Error 0.36 |
| Methotrexate | Change From Baseline to Months 6 and 12 in JSN Scores | Month 6 (n=29,27,28) | 0.35 scores on a scale | Standard Error 0.36 |
| Methotrexate | Change From Baseline to Months 6 and 12 in JSN Scores | Month 12 (n=26,25,22) | 0.71 scores on a scale | Standard Error 0.37 |
Comparison: Month 6p-value: 0.895990% CI: [-0.89, 0.76]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.419390% CI: [-1.25, 0.43]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.576490% CI: [-1.13, 0.56]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.110190% CI: [-1.69, 0.02]mixed model repeated measures analysis
Secondary
Change From Baseline to Months 6 and 12 in mTSS
Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) + erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time frame: Months 6 and 12
Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 6 and 12 in mTSS | Month 6 (n=29,27,28) | 0.44 scores on a scale | Standard Error 0.5 |
| Tofacitinib (CP-690,550) Plus MTX | Change From Baseline to Months 6 and 12 in mTSS | Month 12 (n=26,25,22) | 0.85 scores on a scale | Standard Error 0.51 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 6 and 12 in mTSS | Month 6 (n=29,27,28) | -0.14 scores on a scale | Standard Error 0.51 |
| Tofacitinib (CP-690,550) | Change From Baseline to Months 6 and 12 in mTSS | Month 12 (n=26,25,22) | -0.15 scores on a scale | Standard Error 0.52 |
| Methotrexate | Change From Baseline to Months 6 and 12 in mTSS | Month 6 (n=29,27,28) | 0.93 scores on a scale | Standard Error 0.52 |
| Methotrexate | Change From Baseline to Months 6 and 12 in mTSS | Month 12 (n=26,25,22) | 1.36 scores on a scale | Standard Error 0.54 |
Comparison: Month 6p-value: 0.501990% CI: [-1.68, 0.71]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.146290% CI: [-2.28, 0.14]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.4990% CI: [-1.74, 0.72]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.045990% CI: [-2.76, -0.27]mixed model repeated measures analysis
Secondary
Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])
DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (≤)3.2 implied low disease activity and greater than (\>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (\<)2.6 = remission.
Time frame: Baseline and Months 1, 2, 3, 6, 9, and 12
Population: FAS; n=number of participants assess for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 2 (n=33,33,32) | 2.99 score on a scale | Standard Deviation 1.17 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 12 (n=27,26,20) | 2.49 score on a scale | Standard Deviation 1.02 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 6 (n=31,29,29) | 2.74 score on a scale | Standard Deviation 1.15 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 3 (n=33,33,31) | 3.06 score on a scale | Standard Deviation 1.02 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 1 (n=33,35,37) | 3.71 score on a scale | Standard Deviation 1.15 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Baseline (n=36,36,37) | 5.14 score on a scale | Standard Deviation 0.96 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 9 (n=30,28,24) | 2.37 score on a scale | Standard Deviation 0.98 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 12 (n=27,26,20) | 2.68 score on a scale | Standard Deviation 1.05 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Baseline (n=36,36,37) | 5.48 score on a scale | Standard Deviation 0.78 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 1 (n=33,35,37) | 4.03 score on a scale | Standard Deviation 0.91 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 2 (n=33,33,32) | 3.52 score on a scale | Standard Deviation 1.15 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 3 (n=33,33,31) | 3.46 score on a scale | Standard Deviation 1.09 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 6 (n=31,29,29) | 2.75 score on a scale | Standard Deviation 0.95 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 9 (n=30,28,24) | 2.85 score on a scale | Standard Deviation 0.9 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Baseline (n=36,36,37) | 5.36 score on a scale | Standard Deviation 0.8 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 6 (n=31,29,29) | 3.92 score on a scale | Standard Deviation 1.49 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 1 (n=33,35,37) | 4.65 score on a scale | Standard Deviation 1.07 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 12 (n=27,26,20) | 3.58 score on a scale | Standard Deviation 1.4 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 9 (n=30,28,24) | 3.58 score on a scale | Standard Deviation 1.63 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 3 (n=33,33,31) | 3.87 score on a scale | Standard Deviation 1.43 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) | Month 2 (n=33,33,32) | 4.21 score on a scale | Standard Deviation 1.31 |
Comparison: Baseline90% CI: [-0.56, 0.13]
Comparison: Baseline90% CI: [-0.19, 0.43]
Comparison: Month 190% CI: [-1.38, -0.5]
Comparison: Month 190% CI: [-1.01, -0.22]
Comparison: Month 290% CI: [-1.73, -0.7]
Comparison: Month 290% CI: [-1.2, -0.18]
Comparison: Month 390% CI: [-1.33, -0.29]
Comparison: Month 390% CI: [-0.94, 0.12]
Comparison: Month 690% CI: [-1.75, -0.61]
Comparison: Month 690% CI: [-1.73, -0.63]
Comparison: Month 990% CI: [-1.81, -0.61]
Comparison: Month 990% CI: [-1.33, -0.13]
Comparison: Month 1290% CI: [-1.69, -0.51]
Comparison: Month 1290% CI: [-1.51, -0.29]
Secondary
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])
DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) ≤3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) \<2.6 = remission.
Time frame: Baseline and Months 1, 2, 3, 6, 9, and 12
Population: FAS; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 1 (n=34,35,37) | 4.60 scores on a scale | Standard Deviation 1.37 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 6 (n=30,29,28) | 3.32 scores on a scale | Standard Deviation 1.45 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 3 (n=33,33,31) | 3.66 scores on a scale | Standard Deviation 1.16 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Baseline (n=36,36,37) | 6.25 scores on a scale | Standard Deviation 0.94 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 12 (n=27,26,20) | 3.02 scores on a scale | Standard Deviation 1.22 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 9 (n=30,28,24) | 3.06 scores on a scale | Standard Deviation 1.27 |
| Tofacitinib (CP-690,550) Plus MTX | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 2 (n=32,33,31) | 3.77 scores on a scale | Standard Deviation 1.34 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 3 (n=33,33,31) | 4.12 scores on a scale | Standard Deviation 1.31 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Baseline (n=36,36,37) | 6.50 scores on a scale | Standard Deviation 0.75 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 1 (n=34,35,37) | 4.93 scores on a scale | Standard Deviation 1.12 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 2 (n=32,33,31) | 4.36 scores on a scale | Standard Deviation 1.4 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 6 (n=30,29,28) | 3.51 scores on a scale | Standard Deviation 1.2 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 9 (n=30,28,24) | 3.58 scores on a scale | Standard Deviation 1.1 |
| Tofacitinib (CP-690,550) | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 12 (n=27,26,20) | 3.47 scores on a scale | Standard Deviation 1.36 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 6 (n=30,29,28) | 4.75 scores on a scale | Standard Deviation 1.76 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 1 (n=34,35,37) | 5.51 scores on a scale | Standard Deviation 1.09 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 12 (n=27,26,20) | 4.13 scores on a scale | Standard Deviation 1.76 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 9 (n=30,28,24) | 4.17 scores on a scale | Standard Deviation 1.91 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 3 (n=33,33,31) | 4.63 scores on a scale | Standard Deviation 1.63 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Month 2 (n=32,33,31) | 5.05 scores on a scale | Standard Deviation 1.26 |
| Methotrexate | Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) | Baseline (n=36,36,37) | 6.44 scores on a scale | Standard Deviation 0.78 |
Comparison: Baseline90% CI: [-0.53, 0.15]
Comparison: Baseline90% CI: [-0.24, 0.36]
Comparison: Month 190% CI: [-1.4, -0.42]
Comparison: Month 190% CI: [-1.01, -0.14]
Comparison: Month 290% CI: [-1.82, -0.73]
Comparison: Month 290% CI: [-1.25, -0.13]
Comparison: Month 390% CI: [-1.55, -0.38]
Comparison: Month 390% CI: [-1.12, 0.11]
Comparison: Month 690% CI: [-2.13, -0.72]
Comparison: Month 690% CI: [-1.91, -0.57]
Comparison: Month 990% CI: [-1.84, -0.39]
Comparison: Month 990% CI: [-1.3, 0.13]
Comparison: Month 1290% CI: [-1.84, -0.39]
Comparison: Month 1290% CI: [-1.43, 0.11]
Secondary
Erosion Scores at Months 6 and 12
Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time frame: Months 6 and 12
Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Erosion Scores at Months 6 and 12 | Month 6 (n=29,27,28) | 5.84 scores on a scale | Standard Error 0.24 |
| Tofacitinib (CP-690,550) Plus MTX | Erosion Scores at Months 6 and 12 | Month 12 (n=26,25,22) | 6.10 scores on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) | Erosion Scores at Months 6 and 12 | Month 6 (n=29,27,28) | 5.59 scores on a scale | Standard Error 0.25 |
| Tofacitinib (CP-690,550) | Erosion Scores at Months 6 and 12 | Month 12 (n=26,25,22) | 5.64 scores on a scale | Standard Error 0.26 |
| Methotrexate | Erosion Scores at Months 6 and 12 | Month 6 (n=29,27,28) | 6.26 scores on a scale | Standard Error 0.25 |
| Methotrexate | Erosion Scores at Months 6 and 12 | Month 12 (n=26,25,22) | 6.33 scores on a scale | Standard Error 0.27 |
Comparison: Month 6p-value: 0.235190% CI: [-1, 0.16]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.063190% CI: [-1.27, -0.08]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.536990% CI: [-0.83, 0.38]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.06290% CI: [-1.31, -0.08]mixed model repeated measures analysis
Secondary
Joint Space Narrowing (JSN) Scores at Months 6 and 12
JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time frame: Months 6 and 12
Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Joint Space Narrowing (JSN) Scores at Months 6 and 12 | Month 6 (n=29,27,28) | 5.45 score on a scale | Standard Error 0.34 |
| Tofacitinib (CP-690,550) Plus MTX | Joint Space Narrowing (JSN) Scores at Months 6 and 12 | Month 12 (n=26,25,22) | 5.59 score on a scale | Standard Error 0.35 |
| Tofacitinib (CP-690,550) | Joint Space Narrowing (JSN) Scores at Months 6 and 12 | Month 6 (n=29,27,28) | 5.11 score on a scale | Standard Error 0.35 |
| Tofacitinib (CP-690,550) | Joint Space Narrowing (JSN) Scores at Months 6 and 12 | Month 12 (n=26,25,22) | 5.05 score on a scale | Standard Error 0.36 |
| Methotrexate | Joint Space Narrowing (JSN) Scores at Months 6 and 12 | Month 6 (n=29,27,28) | 5.52 score on a scale | Standard Error 0.36 |
| Methotrexate | Joint Space Narrowing (JSN) Scores at Months 6 and 12 | Month 12 (n=26,25,22) | 5.88 score on a scale | Standard Error 0.37 |
Comparison: Month 6p-value: 0.895990% CI: [-0.89, 0.76]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.419390% CI: [-1.25, 0.43]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.576490% CI: [-1.13, 0.56]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.110190% CI: [-1.69, 0.02]mixed model repeated measures analysis
Secondary
Modified Total Sharp Score (mTSS) at Months 6 and 12
Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) plus (+) erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time frame: Months 6 and 12
Population: Evaluable Set; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Modified Total Sharp Score (mTSS) at Months 6 and 12 | Month 6 (n=29,27,28) | 11.28 score on a scale | Standard Error 0.5 |
| Tofacitinib (CP-690,550) Plus MTX | Modified Total Sharp Score (mTSS) at Months 6 and 12 | Month 12 (n=26,25,22) | 11.70 score on a scale | Standard Error 0.51 |
| Tofacitinib (CP-690,550) | Modified Total Sharp Score (mTSS) at Months 6 and 12 | Month 6 (n=29,27,28) | 10.70 score on a scale | Standard Error 0.51 |
| Tofacitinib (CP-690,550) | Modified Total Sharp Score (mTSS) at Months 6 and 12 | Month 12 (n=26,25,22) | 10.69 score on a scale | Standard Error 0.52 |
| Methotrexate | Modified Total Sharp Score (mTSS) at Months 6 and 12 | Month 6 (n=29,27,28) | 11.77 score on a scale | Standard Error 0.52 |
| Methotrexate | Modified Total Sharp Score (mTSS) at Months 6 and 12 | Month 12 (n=26,25,22) | 12.21 score on a scale | Standard Error 0.54 |
Comparison: Month 6p-value: 0.501990% CI: [-1.68, 0.71]mixed model repeated measures analysis
Comparison: Month 6p-value: 0.146290% CI: [-2.28, 0.14]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.4990% CI: [-1.74, 0.72]mixed model repeated measures analysis
Comparison: Month 12p-value: 0.045990% CI: [-2.76, -0.27]mixed model repeated measures analysis
Secondary
Percentage of Participants With an ACR 50% Improvement (ACR50) Response
ACR50 response: ≥ 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of disease activity, 3) Paricipant's Assessment of Pain, 4) Participant's assessment of functional disability via a HAQ, and 5) CRP at each visit.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assess for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 1 (n=35,35,37) | 22.86 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 2 (n=35,36,37) | 45.71 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 3 (n=35,36,37) | 48.57 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 6 (n=35,36,37) | 57.14 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 9 (n=35,36,37) | 57.14 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 12 (n=35,36,37) | 57.14 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 12 (n=35,36,37) | 44.44 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 1 (n=35,35,37) | 22.86 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 6 (n=35,36,37) | 47.22 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 9 (n=35,36,37) | 44.44 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 2 (n=35,36,37) | 33.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 3 (n=35,36,37) | 50.00 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 2 (n=35,36,37) | 16.22 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 3 (n=35,36,37) | 24.32 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 12 (n=35,36,37) | 29.73 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 6 (n=35,36,37) | 21.62 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 1 (n=35,35,37) | 2.70 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 50% Improvement (ACR50) Response | Month 9 (n=35,36,37) | 29.73 percentage of participants |
Comparison: Month 1p-value: 0.007890% CI: [7.68, 32.62]Normal approximation to the binomial
Comparison: Month 1p-value: 0.007890% CI: [7.68, 32.62]Normal approximation to the binomial
Comparison: Month 2p-value: 0.004490% CI: [12.43, 46.56]Normal approximation to the binomial
Comparison: Month 2p-value: 0.084590% CI: [0.79, 33.43]Normal approximation to the binomial
Comparison: Month 3p-value: 0.027590% CI: [6.14, 42.35]Normal approximation to the binomial
Comparison: Month 3p-value: 0.018690% CI: [7.71, 43.63]Normal approximation to the binomial
Comparison: Month 6p-value: 0.000990% CI: [17.82, 53.22]Normal approximation to the binomial
Comparison: Month 6p-value: 0.016990% CI: [7.95, 43.24]Normal approximation to the binomial
Comparison: Month 9p-value: 0.014790% CI: [8.91, 45.9]Normal approximation to the binomial
Comparison: Month 9p-value: 0.188290% CI: [-3.68, 33.11]Normal approximation to the binomial
Comparison: Month 12p-value: 0.014790% CI: [8.91, 45.9]Normal approximation to the binomial
Comparison: Month 12p-value: 0.188290% CI: [-3.68, 33.11]Normal approximation to the binomial
Secondary
Percentage of Participants With an ACR 70% Improvement (ACR70) Response
ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of Disease Activity, 3) Participant's Assessment of Pain, 4) Participant's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 1 (n=35,35,37) | 8.57 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 2 (n=35,36,37) | 31.43 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 3 (n=35,36,37) | 25.71 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 6 (n=35,36,37) | 34.29 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 9 (n=35,36,37) | 31.43 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 12 (n=35,36,37) | 22.86 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 12 (n=35,36,37) | 33.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 1 (n=35,35,37) | 2.86 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 6 (n=35,36,37) | 30.56 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 9 (n=35,36,37) | 33.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 2 (n=35,36,37) | 22.22 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 3 (n=35,36,37) | 27.78 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 2 (n=35,36,37) | 5.41 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 3 (n=35,36,37) | 10.81 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 12 (n=35,36,37) | 21.62 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 6 (n=35,36,37) | 21.62 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 1 (n=35,35,37) | 0.00 percentage of participants |
| Methotrexate | Percentage of Participants With an ACR 70% Improvement (ACR70) Response | Month 9 (n=35,36,37) | 18.92 percentage of participants |
Comparison: Month 1p-value: 0.0790% CI: [0.78, 16.35]Normal approximation to the binomial
Comparison: Month 1p-value: 0.310290% CI: [-1.77, 7.48]Normal approximation to the binomial
Comparison: Month 2p-value: 0.002790% CI: [11.73, 40.3]Normal approximation to the binomial
Comparison: Month 2p-value: 0.032490% CI: [3.88, 29.75]Normal approximation to the binomial
Comparison: Month 3p-value: 0.096990% CI: [0.13, 29.67]Normal approximation to the binomial
Comparison: Month 3p-value: 0.060690% CI: [2.09, 31.84]Normal approximation to the binomial
Comparison: Month 6p-value: 0.227690% CI: [-4.6, 29.93]Normal approximation to the binomial
Comparison: Month 6p-value: 0.382790% CI: [-7.9, 25.76]Normal approximation to the binomial
Comparison: Month 9p-value: 0.217790% CI: [-4.18, 29.2]Normal approximation to the binomial
Comparison: Month 9p-value: 0.155890% CI: [-2.29, 31.12]Normal approximation to the binomial
Comparison: Month 12p-value: 0.899790% CI: [-14.89, 17.36]Normal approximation to the binomial
Comparison: Month 12p-value: 0.258790% CI: [-5.34, 28.76]Normal approximation to the binomial
Secondary
Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response
ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Participant's Assessment of Pain; Participant's Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS Non-Responder Imputation (NRI) method: participants with missing values were considered to be non-responders. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 1 (n=35,35,37) | 42.86 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 2 (n=35,36,37) | 68.57 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 3 (n=35,36,37) | 77.14 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 6 (n=35,36,37) | 74.29 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 9 (n=35,36,37) | 71.43 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 12 (n=35,36,37) | 71.43 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 12 (n=35,36,37) | 61.11 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 1 (n=35,35,37) | 57.14 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 6 (n=35,36,37) | 66.67 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 9 (n=35,36,37) | 58.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 2 (n=35,36,37) | 61.11 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 3 (n=35,36,37) | 61.11 percentage of participants |
| Methotrexate | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 2 (n=35,36,37) | 40.54 percentage of participants |
| Methotrexate | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 3 (n=35,36,37) | 48.65 percentage of participants |
| Methotrexate | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 12 (n=35,36,37) | 43.24 percentage of participants |
| Methotrexate | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 6 (n=35,36,37) | 45.95 percentage of participants |
| Methotrexate | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 1 (n=35,35,37) | 29.73 percentage of participants |
| Methotrexate | Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response | Month 9 (n=35,36,37) | 43.24 percentage of participants |
Comparison: Month 1p-value: 0.24390% CI: [-5.36, 31.62]Normal approximation to the binomial
Comparison: Month 1p-value: 0.014790% CI: [8.91, 45.9]Normal approximation to the binomial
Comparison: Month 2p-value: 0.012790% CI: [9.51, 46.54]Normal approximation to the binomial
Comparison: Month 2p-value: 0.072490% CI: [1.73, 39.41]Normal approximation to the binomial
Comparison: Month 3p-value: 0.008690% CI: [10.63, 46.35]Normal approximation to the binomial
Comparison: Month 3p-value: 0.280890% CI: [-6.54, 31.47]Normal approximation to the binomial
Comparison: Month 9p-value: 0.011590% CI: [9.81, 46.55]Normal approximation to the binomial
Comparison: Month 9p-value: 0.192190% CI: [-3.94, 34.12]Normal approximation to the binomial
Comparison: Month 12p-value: 0.011590% CI: [9.81, 46.55]Normal approximation to the binomial
Comparison: Month 12p-value: 0.120390% CI: [-1.05, 36.79]Normal approximation to the binomial
Secondary
Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement)
DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL).
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 1 (n=33,35,37) | 75.76 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 2 (n=34,36,37) | 91.18 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 3 (n=34,36,37) | 91.18 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 6 (n=34,36,37) | 88.24 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 9 (n=34,36,37) | 79.41 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 12 (n=34,36,37) | 82.35 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 12 (n=34,36,37) | 72.22 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 1 (n=33,35,37) | 71.43 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 6 (n=34,36,37) | 77.78 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 9 (n=34,36,37) | 69.44 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 2 (n=34,36,37) | 80.56 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 3 (n=34,36,37) | 77.78 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 2 (n=34,36,37) | 56.76 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 3 (n=34,36,37) | 56.76 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 12 (n=34,36,37) | 45.95 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 6 (n=34,36,37) | 54.05 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 1 (n=33,35,37) | 43.24 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) | Month 9 (n=34,36,37) | 45.95 percentage of participants |
Comparison: Month 1p-value: 0.003290% CI: [14.34, 50.68]Normal approximation to the binomial
Comparison: Month 1p-value: 0.011590% CI: [9.81, 46.55]Normal approximation to the binomial
Comparison: Month 2p-value: 0.000290% CI: [18.81, 50.02]Normal approximation to the binomial
Comparison: Month 2p-value: 0.023190% CI: [6.55, 41.03]Normal approximation to the binomial
Comparison: Month 3p-value: 0.000290% CI: [18.81, 50.02]Normal approximation to the binomial
Comparison: Month 3p-value: 0.049390% CI: [3.43, 38.61]Normal approximation to the binomial
Comparison: Month 6p-value: 0.000590% CI: [17.92, 50.43]Normal approximation to the binomial
Comparison: Month 6p-value: 0.02790% CI: [6.07, 41.37]Normal approximation to the binomial
Comparison: Month 9p-value: 0.001890% CI: [15.8, 51.12]Normal approximation to the binomial
Comparison: Month 9p-value: 0.036390% CI: [5.02, 41.96]Normal approximation to the binomial
Comparison: Month 12p-value: 0.000590% CI: [19.16, 53.64]Normal approximation to the binomial
Comparison: Month 12p-value: 0.017790% CI: [8.04, 44.5]Normal approximation to the binomial
Secondary
Percentage of Participants With DAS28-3 (CRP) Score <2.6
DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) \<2.6 implied remission.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 1 (n=33,35,37) | 18.18 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 2 (n=34,36,37) | 35.29 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 3 (n=34,36,37) | 32.35 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 6 (n=34,36,37) | 47.06 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 9 (n=34,36,37) | 50.00 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 12 (n=34,36,37) | 47.06 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 12 (n=34,36,37) | 33.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 1 (n=33,35,37) | 5.71 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 6 (n=34,36,37) | 33.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 9 (n=34,36,37) | 38.89 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 2 (n=34,36,37) | 16.67 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 3 (n=34,36,37) | 22.22 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 2 (n=34,36,37) | 8.11 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 3 (n=34,36,37) | 13.51 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 12 (n=34,36,37) | 13.51 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 6 (n=34,36,37) | 16.22 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 1 (n=33,35,37) | 5.41 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score <2.6 | Month 9 (n=34,36,37) | 18.92 percentage of participants |
Comparison: Month 1p-value: 0.095990% CI: [0.15, 25.4]Normal approximation to the binomial
Comparison: Month 1p-value: 0.954490% CI: [-8.58, 9.19]Normal approximation to the binomial
Comparison: Month 2p-value: 0.003690% CI: [11.81, 42.55]Normal approximation to the binomial
Comparison: Month 2p-value: 0.26490% CI: [-4.04, 21.16]Normal approximation to the binomial
Comparison: Month 3p-value: 0.054490% CI: [2.72, 34.95]Normal approximation to the binomial
Comparison: Month 3p-value: 0.32990% CI: [-5.96, 23.38]Normal approximation to the binomial
Comparison: Month 6p-value: 0.003290% CI: [13.59, 48.09]Normal approximation to the binomial
Comparison: Month 6p-value: 0.084590% CI: [0.79, 33.43]Normal approximation to the binomial
Comparison: Month 9p-value: 0.003790% CI: [13.44, 48.72]Normal approximation to the binomial
Comparison: Month 9p-value: 0.05490% CI: [2.91, 37.02]Normal approximation to the binomial
Comparison: Month 12p-value: 0.00190% CI: [16.7, 50.39]Normal approximation to the binomial
Comparison: Month 12p-value: 0.040190% CI: [3.92, 35.71]Normal approximation to the binomial
Secondary
Percentage of Participants With DAS28-3 (CRP) Score ≤3.2
DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 1 (n=33,35,37) | 33.33 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 2 (n=34,36,37) | 50.00 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 3 (n=34,36,37) | 50.00 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 6 (n=34,36,37) | 61.76 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 9 (n=34,36,37) | 64.71 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 12 (n=34,36,37) | 61.76 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 12 (n=34,36,37) | 50.00 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 1 (n=33,35,37) | 17.14 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 6 (n=34,36,37) | 55.56 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 9 (n=34,36,37) | 58.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 2 (n=34,36,37) | 36.11 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 3 (n=34,36,37) | 41.67 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 2 (n=34,36,37) | 21.62 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 3 (n=34,36,37) | 21.62 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 12 (n=34,36,37) | 27.03 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 6 (n=34,36,37) | 27.03 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 1 (n=33,35,37) | 10.81 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 | Month 9 (n=34,36,37) | 29.33 percentage of participants |
Comparison: Month 1p-value: 0.019790% CI: [6.62, 38.42]Normal approximation to the binomial
Comparison: Month 1p-value: 0.437990% CI: [-7.09, 19.76]Normal approximation to the binomial
Comparison: Month 2p-value: 0.009390% CI: [10.4, 46.34]Normal approximation to the binomial
Comparison: Month 2p-value: 0.166990% CI: [-2.75, 31.73]Normal approximation to the binomial
Comparison: Month 3p-value: 0.009390% CI: [10.4, 46.34]Normal approximation to the binomial
Comparison: Month 3p-value: 0.059690% CI: [2.53, 37.55]Normal approximation to the binomial
Comparison: Month 6p-value: 0.001790% CI: [16.51, 52.96]Normal approximation to the binomial
Comparison: Month 6p-value: 0.009790% CI: [10.36, 46.69]Normal approximation to the binomial
Comparison: Month 9p-value: 0.001690% CI: [16.68, 53.26]Normal approximation to the binomial
Comparison: Month 9p-value: 0.010290% CI: [10.28, 46.91]Normal approximation to the binomial
Comparison: Month 12p-value: 0.001790% CI: [16.51, 52.96]Normal approximation to the binomial
Comparison: Month 12p-value: 0.038190% CI: [4.74, 41.19]Normal approximation to the binomial
Secondary
Percentage of Participants With DAS28-4 (ESR) <2.6
DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) \<2.6 implied remission.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 1 (n=34,35,37) | 5.88 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 2 (n=34,36,37) | 17.65 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 3 (n=34,36,37) | 23.53 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 6 (n=34,36,37) | 29.41 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 9 (n=34,36,37) | 35.29 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 12 (n=34,36,37) | 32.35 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 12 (n=34,36,37) | 19.44 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 1 (n=34,35,37) | 2.86 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 6 (n=34,36,37) | 13.89 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 9 (n=34,36,37) | 13.89 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 2 (n=34,36,37) | 5.56 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 3 (n=34,36,37) | 2.78 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 2 (n=34,36,37) | 2.70 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 3 (n=34,36,37) | 13.51 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 12 (n=34,36,37) | 13.51 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 6 (n=34,36,37) | 13.51 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 1 (n=34,35,37) | 0.00 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) <2.6 | Month 9 (n=34,36,37) | 16.22 percentage of participants |
Comparison: Month 1p-value: 0.144990% CI: [-0.75, 12.52]Normal approximation to the binomial
Comparison: Month 1p-value: 0.310290% CI: [-1.77, 7.48]Normal approximation to the binomial
Comparison: Month 2p-value: 0.034290% CI: [3.32, 26.55]Normal approximation to the binomial
Comparison: Month 2p-value: 0.5490% CI: [-4.8, 10.51]Normal approximation to the binomial
Comparison: Month 3p-value: 0.275990% CI: [-5.1, 25.13]Normal approximation to the binomial
Comparison: Month 3p-value: 0.085990% CI: [-21.02, -0.45]Normal approximation to the binomial
Comparison: Month 6p-value: 0.098590% CI: [0.06, 31.73]Normal approximation to the binomial
Comparison: Month 6p-value: 0.962890% CI: [-12.86, 13.61]Normal approximation to the binomial
Comparison: Month 9p-value: 0.061290% CI: [2.31, 35.84]Normal approximation to the binomial
Comparison: Month 9p-value: 0.780790% CI: [-16.08, 11.43]Normal approximation to the binomial
Comparison: Month 12p-value: 0.054490% CI: [2.72, 34.95]Normal approximation to the binomial
Comparison: Month 12p-value: 0.493790% CI: [-8.32, 20.18]Normal approximation to the binomial
Secondary
Percentage of Participants With DAS28-4 (ESR) ≤3.2
DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity.
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 1 (n=34,35,37) | 20.59 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 2 (n=34,36,37) | 35.29 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 3 (n=34,36,37) | 32.35 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 6 (n=34,36,37) | 41.18 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 9 (n=34,36,37) | 44.12 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 12 (n=34,36,37) | 50.00 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 12 (n=34,36,37) | 30.56 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 1 (n=34,35,37) | 8.57 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 6 (n=34,36,37) | 27.78 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 9 (n=34,36,37) | 33.33 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 2 (n=34,36,37) | 13.89 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 3 (n=34,36,37) | 30.56 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 2 (n=34,36,37) | 8.11 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 3 (n=34,36,37) | 13.51 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 12 (n=34,36,37) | 16.22 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 6 (n=34,36,37) | 18.92 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 1 (n=34,35,37) | 2.70 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) ≤3.2 | Month 9 (n=34,36,37) | 18.92 percentage of participants |
Comparison: Month 1p-value: 0.01690% CI: [5.66, 30.1]Normal approximation to the binomial
Comparison: Month 1p-value: 0.279890% CI: [-3.06, 14.8]Normal approximation to the binomial
Comparison: Month 2p-value: 0.003690% CI: [11.81, 42.55]Normal approximation to the binomial
Comparison: Month 2p-value: 0.428790% CI: [-6.23, 17.79]Normal approximation to the binomial
Comparison: Month 3p-value: 0.054490% CI: [2.72, 34.95]Normal approximation to the binomial
Comparison: Month 3p-value: 0.073290% CI: [1.39, 32.69]Normal approximation to the binomial
Comparison: Month 6p-value: 0.03690% CI: [4.79, 39.72]Normal approximation to the binomial
Comparison: Month 6p-value: 0.368890% CI: [-7.35, 25.07]Normal approximation to the binomial
Comparison: Month 9p-value: 0.018290% CI: [7.63, 42.76]Normal approximation to the binomial
Comparison: Month 9p-value: 0.155890% CI: [-2.29, 31.12]Normal approximation to the binomial
Comparison: Month 12p-value: 0.001290% CI: [16.51, 51.05]Normal approximation to the binomial
Comparison: Month 12p-value: 0.142690% CI: [-1.74, 30.42]Normal approximation to the binomial
Secondary
Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement)
DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL).
Time frame: Months 1, 2, 3, 6, 9, and 12
Population: FAS NRI; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 1 (n=34,35,37) | 67.65 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 2 (n=32,33,31) | 85.29 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 3 (n=33,33,31) | 91.18 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 6 (n=30,29,28) | 85.29 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 9 (n=30,28,24) | 82.35 percentage of participants |
| Tofacitinib (CP-690,550) Plus MTX | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 12 (n=27,26,20) | 79.41 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 12 (n=27,26,20) | 69.44 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 1 (n=34,35,37) | 62.86 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 6 (n=30,29,28) | 77.78 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 9 (n=30,28,24) | 72.22 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 2 (n=32,33,31) | 69.44 percentage of participants |
| Tofacitinib (CP-690,550) | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 3 (n=33,33,31) | 69.44 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 2 (n=32,33,31) | 59.46 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 3 (n=33,33,31) | 51.35 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 12 (n=27,26,20) | 45.95 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 6 (n=30,29,28) | 51.35 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 1 (n=34,35,37) | 29.73 percentage of participants |
| Methotrexate | Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) | Month 9 (n=30,28,24) | 45.95 percentage of participants |
Comparison: Month 1p-value: 0.000590% CI: [19.83, 55.99]Normal approximation to the binomial
Comparison: Month 1p-value: 0.002890% CI: [14.87, 51.38]Normal approximation to the binomial
Comparison: Month 2p-value: 0.010590% CI: [9.21, 42.45]Normal approximation to the binomial
Comparison: Month 2p-value: 0.3790% CI: [-8.33, 28.3]Normal approximation to the binomial
Comparison: Month 3p-value: <0.000190% CI: [24.11, 55.53]Normal approximation to the binomial
Comparison: Month 3p-value: 0.107690% CI: [-0.4, 36.59]Normal approximation to the binomial
Comparison: Month 6p-value: 0.000890% CI: [17.13, 50.75]Normal approximation to the binomial
Comparison: Month 6p-value: 0.013990% CI: [8.74, 44.1]Normal approximation to the binomial
Comparison: Month 9p-value: 0.000590% CI: [19.16, 53.64]Normal approximation to the binomial
Comparison: Month 9p-value: 0.017790% CI: [8.04, 44.5]Normal approximation to the binomial
Comparison: Month 12p-value: 0.001890% CI: [15.8, 51.12]Normal approximation to the binomial
Comparison: Month 12p-value: 0.036390% CI: [5.02, 41.96]Normal approximation to the binomial