Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)
- Conditions
- Rheumatoid Arthritis
- Interventions
- Drug: Placebo tofacitinib plus Methotrexate
- Registration Number
- NCT01164579
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 109
- Adult patients with moderate to severe early rheumatoid arthritis (< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tofacitinib (CP 690,550) 10 mg BID plus MTX Tasocitinib plus Methotrexate - Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX Tofacitinib plus placebo methotrexate - Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk Placebo tofacitinib plus Methotrexate -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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.
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.
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 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.
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 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.
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.
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 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 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.
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 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.
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 <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.
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.
Trial Locations
- Locations (38)
Hospital Angeles Mocel
🇲🇽Mexico D.F., Mexico
Nemocnice na Frantisku s poliklinikou
🇨🇿Praha 1, Czech Republic
Nzoz "Nasz Lekarz"
🇵🇱Torun, Poland
St. Petersburg Arthritis Center
🇺🇸St. Petersburg, Florida, 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
ArthroCare, Arthritis Care & Research, PC
🇺🇸Gilbert, Arizona, United States
Oklahoma Medical Research Foundation
🇺🇸Oklahoma City, Oklahoma, United States
DMI Research, Inc.
🇺🇸Pinellas Park, Florida, 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
Consultorios Reumatologicos Pampa
🇦🇷Buenos Aires, Argentina
Hospital Base Valdivia
🇨🇱Valdivia, Region XIV, Chile
Consulta Privada Dr. Juan Ignacio Vargas
🇨🇱Osorno, X Region, Chile
General Hospital Sveti Duh
🇭🇷Zagreb, Croatia
University Hospital Centre Split,Department for Internal Medicine, Division of Clinical Rheumatology
🇭🇷Split, Croatia
ARTMEDI UPD s r.o.
🇨🇿Hostivice, Czech Republic
DC Mediscan
🇨🇿Praha 11 - Chodov, Czech Republic
Uherskohradistska nemocnice, a.s.
🇨🇿Uherske Hradiste, Czech Republic
Nemocnice Atlas, a.s.
🇨🇿Zlin, Czech Republic
Revmatologicky ustav
🇨🇿Praha 2, Czech Republic
Nemocnice na Frantisku
🇨🇿Praha 1, Czech Republic
Drug Research Center Kft.
🇭🇺Balatonfured, Hungary
Orszagos Reumatologiai es Fizioterapias Intezet
🇭🇺Budapest, Hungary
PV-Medical s.r.o.
🇨🇿Zlin, Czech Republic
Synexus Magyarorszag Kft.
🇭🇺Budapest, Hungary
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Reumatologiai Tanszek
🇭🇺Debrecen, Hungary
Petz Aladar Megyei Oktato Korhaz/Reumatologiai es Mozgasszervi Rehabilitacios Centrum
🇭🇺Gyor, Hungary
Centro de Investigacion y Tratamiento Reumatologico S.C.
🇲🇽Mexico, D. F., Mexico
Investigacion y Biomedicina de Chihuahua S.C
🇲🇽Chihuahua, Mexico
Centro de Investigacion y Tratamiento Reumatologico SC
🇲🇽Mexico, Distrito Federal, Mexico
Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
🇲🇽San Luis Potosi, Mexico
Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj
🇵🇱Poznan, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych J.
🇵🇱Bialystok, Poland
Mindful Medical Research
🇵🇷San Juan, Puerto Rico
San Juan Arthritis & Research Center
🇵🇷San Juan, Puerto Rico