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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
109
Tofacitinib (CP 690,550) 10 mg BID, tablets + methotrexate (MTX) 10 mg/wk to 20 mg/wk, titrated over 2 months
Tofacitinib (CP-90,550) 10 mg BID, tablets. Placebo to match methotrexate (MTX) capsules titrated as in Treatment Arm 1.
Methotrexate (MTX) 10 mg/wk to 20 mg/wk, capsules, titrated over 2 months. Placebo in tablets to match tofacitinib
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
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
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.
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ArthroCare, Arthritis Care & Research, PC
Gilbert, Arizona, United States
Talbert Medical Group
Huntington Beach, California, United States
Inland Rheumatology Clinical Trials, Inc.
Upland, California, United States
Millennium Research
Ormond Beach, Florida, United States
DMI Research, Inc.
Pinellas Park, Florida, United States
St. Petersburg Arthritis Center
St. Petersburg, Florida, United States
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States
Office of John P. Lavery, MD, PA
Allen, Texas, United States
OMI - Organización Médica de Investigación
Buenos Aires, Argentina
Saint Dennis Medical Group S.A.
Buenos Aires, Argentina
...and 30 more locations
Time frame: Months 1, 6, and 12
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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