Comparing The Effectiveness And Safety Of 2 Doses Of An Experimental Drug, CP-690,550, To Methotrexate (MTX) In Patients With Rheumatoid Arthritis Who Have Not Previously Received MTX

Study Overview
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Brief Summary
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This study is designed to compare the effectiveness of the experimental drug, CP-690,550, to methotrexate in preventing joint damage and improving symptoms of rheumatoid arthritis. This study will also compare the safety of CP-690,550 with methotrexate.

Official Title
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Phase 3 Randomized, Double-blind Study Of The Efficacy And Safety Of 2 Doses Of Cp-690,550 Compared To Methotrexate In Methotrexate Navie Patients With Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: CP-690,550
* Drug: CP-690,550
* Drug: Disease-modifying antirheumatic drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with moderate to severe RA (Rheumatoid Arthritis) who have not been treated with methotrexate. Diagnosis of RA based on the American College of Rheumatology 1987 revised criteria. Active disease as defined by both >=6 tender or painful joints on motion and >= 6 joints swollen; and either an erythrocyte sedimentation rate (ESR) > 28 mm or a C-reactive protein (CRP) concentration > 7 mg/dL Exclusion Criteria: Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.2 x 109/L; Platelet count <100 x 109/L History of any other rheumatic autoimmune disease other than Sjogren's syndrome No malignancy or history of malignancy History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug No chronic liver disease, recent or active hepatitis or other contraindication to methotrexate therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg BID CP-690,550<br> | Drug: CP-690,550<br>* Oral tablets administered at a dose of 5 mg BID for 24 months<br>|
| Experimental: 10 mg BID CP-690,550<br> | Drug: CP-690,550<br>* Oral tablets administered at a dose of 10 mg BID for 24 months<br>|
| Active Comparator: methotrexate<br> | Drug: Disease-modifying antirheumatic drug<br>* Oral capsules,administered as 10 mg per week for 4 weeks titrated to 15 mg per week for 4 weeks, then titrated to 20 mg week for 24 months<br>* Other names: DMARD, MTX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Total Sharp Score (mTSS) at Month 6 | mTSS: sum of erosion and joint space narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score). | Month 6 | 
| Change From Baseline at Month 6 in mTSS | mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score). An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement. | Month 6 | 
| Percentage of Participants Achieving American College of Rheumatology 70 (ACR70) Response at Month 6 | ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender joints count (TJC) or swollen joints count (SJC) and ≥70% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of the Health Assessment Questionnaire [HAQ]), and 5) C-reactive protein (CRP). | Month 6 | 
| Absolute Blood Pressure (BP) Values (mmHg) | BP: pressure exerted by the blood upon the walls of the blood vessels and especially arteries, usually measured on the radial artery using a sphygmomanometer. Systolic BP: the highest arterial blood pressure of a cardiac cycle occurring immediately after systole of the left ventricle of the heart. Diastolic BP: the lowest arterial blood pressure of a cardiac cycle occurring during diastole of the heart. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, and 24 | 
| Change From Baseline in BP Values (mmHg) | BP: pressure exerted by the blood upon the walls of the blood vessels and especially arteries, usually measured on the radial artery using a sphygmomanometer. Systolic BP: the highest arterial blood pressure of a cardiac cycle occurring immediately after systole of the left ventricle of the heart. Diastolic BP: the lowest arterial blood pressure of a cardiac cycle occurring during diastole of the heart. | Months 1, 2, 3, 6, 9, 12, 15, 18, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mTSS Score at Baseline, Months 12 and 24 | mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score). | Baseline, Months 12 and 24 | 
| Change From Baseline in mTSS Score at Months 12 and 24 | mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score). An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement. | Months 12 and 24 | 
| Percentage of Participants With no Progression in mTSS at Months 6, 12, and 24 | mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score). A increase of less than or equal to (≤)0.5 in mTSS is considered to be no progression in the mTSS. | Months 6, 12, and 24 | 
| Percentage of Participants With no Worsening in Erosion Score (Increase ≤0.5) at Months 6, 12, and 24 | Joint erosion score: erosion severity in 44 joints (16 per hand, 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, maximum erosion score was 280. An increase of ≤0.5 in Erosion Score is considered to be 'no worsening' in the Erosion Score. | Months 6, 12, and 24 | 
| Erosion Scores | Joint erosion score: erosion severity in 44 joints (16 per hand, 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, maximum erosion score was 280. | Baseline, Months 6, 12, and 24 | 
| JSN Scores | JSN score: severity of JSN in 42 joints (15 per hand and 6 per foot), including subluxation, scored from 0 (no/normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation). Maximum JSN score was 168. | Baseline, Months 6, 12, and 24 | 
| Change From Baseline in Erosion Scores | Joint erosion score: erosion severity in 44 joints (16 per hand, 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, maximum erosion score was 280. Change = score at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. | Months 6, 12, and 24 | 
| Change From Baseline in JSN Scores | JSN score: severity of JSN in 42 joints (15 per hand and 6 per foot), including subluxation, scored from 0 (no/normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation). Maximum JSN score was 168. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. | Months 6, 12, and 24 | 
| Percentage of Participants Achieving an ACR70 Response | ACR70 response: ≥70% improvement in TJC or SJC and ≥70% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of HAQ), and 5) CRP. | Months 1, 2, 3, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants Achieving an ACR20 Response | ACR20 response: ≥20% improvement in TJC or SJC and ≥20% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of HAQ), and 5) CRP. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants Achieving an ACR50 Response | ACR50 response: ≥50% improvement in TJC or SJC and ≥50% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of HAQ), and 5) CRP. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Tender Joints Count (TJC) | Sixty-eight (68) joints were assessed by a blinded joint assessor to determine the number of joints considered tender or painful. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not assessed. 68 joints to be assessed were: upper body (temporomandibular, sternoclavicular, acromioclavicular); upper extremity: shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as one unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal (IP), proximal interphalangeals (PIP II, III, IV, V), distal interphalangeals (DIP II, III, IV, V); lower extremity: hip, knee, ankle, tarsus (includes subtalar, transverse tarsal and tarsometatarsal considered as one unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe IP, proximal and distal interphalangeals combined (PIP II, III, IV, V). | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in TJC | Sixty-eight (68) joints were assessed by a blinded joint assessor to determine the number of joints considered tender or painful. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not assessed. 68 joints to be assessed were: upper body (temporomandibular, sternoclavicular, acromioclavicular); upper extremity: shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as one unit), MCP (I, II, III, IV, V), thumb IP, PIP (II, III, IV, V), DIP (II, III, IV, V); lower extremity: hip, knee, ankle, tarsus (includes subtalar, transverse tarsal and tarsometatarsal considered as one unit), MTP (I, II, III, IV, V), great toe IP, proximal and distal interphalangeals combined (PIP II, III, IV, V). | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Swollen Joints Count (SJC) | Sixty-six (66) joints were assessed by a blinded joint assessor for swelling using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not assessed. 66 joints assessed were: upper body (temporomandibular, sternoclavicular, acromioclavicular); upper extremity: shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as one unit), MCP (I, II, III, IV, V), thumb IP, PIP (II, III, IV, V), DIP (II, III, IV, V); lower extremity: knee, ankle, tarsus (includes subtalar, transverse tarsal and tarsometatarsal considered as one unit), MTP (I, II, III, IV, V), great toe IP, proximal and distal interphalangeals combined (PIP II, III, IV, V). | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in SJC | Sixty-six (66) joints were assessed by a blinded joint assessor for swelling using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not assessed. 66 joints assessed were: upper body (temporomandibular, sternoclavicular, acromioclavicular); upper extremity: shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as one unit), MCP (I, II, III, IV, V), thumb IP, PIP (II, III, IV, V), DIP (II, III, IV, V); lower extremity: knee, ankle, tarsus (includes subtalar, transverse tarsal and tarsometatarsal considered as one unit), MTP (I, II, III, IV, V), great toe IP, proximal and distal interphalangeals combined (PIP II, III, IV, V). | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Patient Assessment of Arthritis Pain | Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) visual analogue scale (VAS), where 0 mm=no pain and 100 mm=most severe pain. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in Patient Assessment of Arthritis Pain | Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm=no pain and 100 mm=most severe pain. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Physician Global Assessment of Arthritis | Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm=very good and 100 mm=very bad. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in Physician Global Assessment of Arthritis | Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm=very good and 100 mm=very bad. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Patient Global Assessment of Arthritis | Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 mm VAS where 0=very well and 100=very poorly. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in Patient Global Assessment of Arthritis | Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 mm VAS where 0=very well and 100=very poorly. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| C-Reactive Protein | CRP measured in milligrams per liter (mg/L) | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in CRP | Change from Baseline in CRP measured in mg/L. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3) CRP | DAS28-3(CRP) was calculated from the SJC and TJC using 28-joints count and CRP (mg/L). Total score range: 0 to approximately 10, higher score indicated more disease activity. DAS28-3(CRP) less than or equal to (≤)3.2 implied low disease activity, greater than (>)3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-3(CRP) less than (<)2.6 = remission. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) | DAS28-4(ESR) was calculated from SJC and TJC using 28 joints count, ESR (millimeter/hour [mm/hour]) and patient's global assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to approximately 10, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4(ESR) <2.6 = remission. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in DAS28-3(CRP) | DAS28-3(CRP) was calculated from the SJC and TJC using 28-joints count and CRP (mg/L). Total score range: 0 to approximately 10, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-3(CRP) <2.6 = remission. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in DAS28-4(ESR) | DAS28-4(ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and patient's global assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to approximately 10, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4(ESR) <2.6 = remission. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With DAS28-3(CRP) ≤3.2 | DAS28-3(CRP) was calculated from the SJC and TJC using 28-joints count and CRP (mg/L). Total score range: 0 to approximately 10, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-3(CRP) <2.6 = remission. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With DAS28-4(ESR) ≤3.2 | DAS28-4(ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and patient's global assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to approximately 10, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4(ESR) <2.6 = remission. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With DAS28-3(CRP) <2.6 | DAS28-3(CRP) was calculated from the SJC and TJC using 28-joints count and CRP (mg/L). Total score range: 0 to approximately 10, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-3(CRP) <2.6 = remission. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With DAS28-4(ESR) <2.6 | DAS28-4(ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and patient's global assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to approximately 10, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4(ESR) <2.6 = remission. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With DAS28-3(CRP) Response (Good or Moderate Improvement) | DAS28-3(CRP) was calculated from the SJC and TJC using 28-joints count and CRP (mg/L). Total score range: 0 to approximately 10, 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). | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With DAS28-4(ESR) Response (Good or Moderate Improvement) | DAS28-4(ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and patient's global assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to approximately 10, 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). | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With an ACR70 Response Sustained at Least 6 Months | ACR70 response: ≥70% improvement in TJC or SJC and ≥70% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of HAQ), and 5) CRP. | Months 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With Consecutive Visits of ACR20 Response by Number of Consecutive Visits | ACR20 response: ≥20% improvement in TJC or SJC and ≥20% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of HAQ), and 5) CRP. | Months 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With Consecutive Visits of ACR50 Response by Number of Consecutive Visits | ACR50 response: ≥50% improvement in TJC or SJC and ≥50% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of HAQ), and 5) CRP. | Months 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With Consecutive Visits of ACR70 Response by Number of Consecutive Visits | ACR70 response: ≥70% improvement in TJC or SJC and ≥70% improvement in at least 3 of 5 remaining ACR core measures: 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 (disability index of HAQ), and 5) CRP. | Months 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With Consecutive Visits of DAS28-3(CRP) <2.6 by Number of Consecutive Visits | DAS28-3(CRP) was calculated from the SJC and TJC using 28-joints count and CRP (mg/L). Total score range: 0 to approximately 10, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-3(CRP) <2.6 = remission. | Months 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With Consecutive Visits of DAS28-4(ESR) <2.6 by Number of Consecutive Visits | DAS28-4(ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and patient's global assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to approximately 10, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4(ESR) <2.6 = remission. | Months 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Health Assessment Questionnaire Disability Index (HAQ-DI) | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom, arise, eat, walk, hygiene, common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in HAQ-DI Score | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom, arise, eat, walk, hygiene, common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With at Least 0.22 Improvement in HAQ-DI Score | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom, arise, eat, walk, hygiene, common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With at Least 0.3 Improvement in HAQ-DI Score | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom, arise, eat, walk, hygiene, common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Percentage of Participants With at Least 0.5 Improvement in HAQ-DI | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom, arise, eat, walk, hygiene, common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Short Form 36 (SF-36) Mental Component Score | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) and is reported as 2 summary scores; physical component score and mental component score. Total score range for the summary scores = 0-100, where higher score represents higher level of functioning. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| SF-36 Physical Component Score | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) and is reported as 2 summary scores; physical component score and mental component score. Total score range for the summary scores = 0-100, where higher score represents higher level of functioning. | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in SF-36 Mental Component Score | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) and is reported as 2 summary scores; physical component score and mental component score. Total score range for the summary scores = 0-100, where higher score represents higher level of functioning. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in SF-36 Physical Component Score | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning) and is reported as 2 summary scores; physical component score and mental component score. Total score range for the summary scores = 0-100, where higher score represents higher level of functioning. | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| SF-36 Domain Scores | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in SF-36 Domain Scores | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Work Limitation Questionnaire (WLQ) Score | WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (5-items); Physical Demands scale (6-item); Mental-Interpersonal Demands Scale (9-items); Output Demands scale (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). | Baseline and Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in WLQ Scores | WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (5 items); Physical Demands scale (6 items); Mental-Interpersonal Demands Scale (9 items); Output Demands scale (5 items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| WLQ Work Loss Index Score | WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (5-items); Physical Demands scale (6-item); Mental-Interpersonal Demands Scale (9-items); Output Demands scale (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index, which represented percentage of lost work over time period relative to a normative population, was derived (total score:0 [no loss] to 100 [complete loss of work]). | Baseline and Months 3, 6, and 12 | 
| Change From Baseline in WLQ Work Loss Index Score | WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (5-items); Physical Demands scale (6-item); Mental-Interpersonal Demands Scale (9-items); Output Demands scale (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index, which represented percentage of lost work over time period relative to a normative population, was derived (total score:0 [no loss] to 100 [complete loss of work]). | Months 3, 6, 12, 15, 18, 21, and 24 | 
| European Quality of Life (EuroQol) Five Dimensions (EQ-5D) Health State Profile Utility Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. | Baseline and Months 3, 6, 12, 18, and 24 | 
| Change From Baseline in EQ-5D Health State Profile Utility Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. | Months 3, 6, 12, 18, and 24 | 
| Work Productivity and Healthcare Resource Utilization (HCRU) at Baseline and Months 3 and 6 | Rheumatoid Arthritis (RA)-HCRU assessed healthcare usage during last 3 months for direct, indirect medical cost domains. Direct cost: visit to doctor, non-medical practitioner, nursing home, hospital, surgery, emergency room (ER) treatment, diagnostic tests, overnight stay, home healthcare services, aids/devices used. Indirect costs associated with functional disability: employment status, willingness to work, work disability due to RA, sick leave, part time work, ability to perform chores, chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale; higher score=higher medical cost. | Baseline and Months 3 and 6 | 
| Work Productivity and Healthcare Resource Utilization (HCRU) at Months 12, 18, and 24 | RA-HCRU assessed healthcare usage during last 3 months for direct, indirect medical cost domains. Direct cost: visit to doctor, non-medical practitioner, nursing home, hospital, surgery, ER treatment, diagnostic tests, overnight stay, home healthcare services, aids/devices used. Indirect costs associated with functional disability: employment status, willingness to work, work disability due to RA, sick leave, part time work, ability to perform chores, chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale; higher score=higher medical cost. | Months 12, 18, and 24 | 
| Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Baseline and Months 3 and 6 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of events including visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported. | Baseline and Months 3 and 6 | 
| Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Months 12, 18, and 24 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of events including visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported. | Months 12, 18, and 24 | 
| Number of Days as Assessed Using RA-HCRU at Baseline and Months 3 and 6 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends. | Baseline and Months 3 and 6 | 
| Number of Days as Assessed Using RA-HCRU at Months 12, 18, and 24 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends. | Months 12, 18, and 24 | 
| Number of Hours Per Day as Assessed Using RA-HCRU at Baseline and Months 3 and 6 | RA-HCRU assessed healthcare (HC) usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home healthcare services, chores done by housekeeper, chores done by family or friends, work done, and work missed were reported. | Baseline and Months 3 and 6 | 
| Number of Hours Per Day as Assessed Using RA-HCRU at Months 12, 18, and 24 | RA-HCRU assessed HC usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home healthcare services, chores done by housekeeper, chores done by family or friends, work done, and work missed were reported. | Months 12, 18, and 24 | 
| Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU | Work performance of participants on number of days bothered was based on a 0 to 10-point scale, where higher score indicated lower work performance. | Baseline, Months 3, 6, 12, 18, and 24 | 
| Change From Baseline in Work Productivity and HCRU at Months 3 and 6 | RA-HCRU assessed HC usage during last 3 months for direct, indirect medical cost domains. Direct cost: visit to doctor, non-medical practitioner, nursing home, hospital, surgery, ER treatment, diagnostic tests, overnight stay, home healthcare services, aids/devices used. Indirect costs associated with functional disability: employment status, willingness to work, work disability due to RA, sick leave, part time work, ability to perform chores, chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale; higher score=higher medical cost. | Months 3 and 6 | 
| Change From Baseline in Work Productivity and HCRU at Months 12, 18, and 24 | RA-HCRU assessed HC usage during last 3 months for direct, indirect medical cost domains. Direct cost: visit to doctor, non-medical practitioner, nursing home, hospital, surgery, ER treatment, diagnostic tests, overnight stay, home healthcare services, aids/devices used. Indirect costs associated with functional disability: employment status, willingness to work, work disability due to RA, sick leave, part time work, ability to perform chores, chores done by family/friends/housekeeper. Assessment was based on 0 to 2-point scale; higher score=higher medical cost. | Months 12, 18, and 24 | 
| Change From Baseline in Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Months 3 and 6 | RA-HCRU assessed healthcare usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of events including visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported. | Months 3 and 6 | 
| Change From Baseline in Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Months 12, 18, and 24 | RA-HCRU assessed HC usage during previous 3 months for direct or indirect medical cost domains. Any RA/non-RA related number of events including visits to doctor, non-medical practitioner, hospital ER treatment, hospitalizations, number of surgeries, diagnostic tests, and devices/aids used were reported. | Months 12, 18, and 24 | 
| Change From Baseline in Number of Days as Assessed Using RA-HCRU at Months 3 and 6 | RA-HCRU assessed HC usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends. | Months 3 and 6 | 
| Change From Baseline in Number of Days as Assessed Using RA-HCRU at Months 12, 18, and 24 | RA-HCRU assessed HC usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of days spent in hospital, nursing home, aids/devices used, on sick leave, work per week, performed part time work, performed paid work, chores done by housekeeper and chores done by family/friends. | Months 12, 18, and 24 | 
| Change From Baseline in Number of Hours Per Day as Assessed Using RA-HCRU at Months 3 and 6 | RA-HCRU assessed HC usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home HC services, chores done by housekeeper, chores done by family or friends, work done and work missed were reported. | Months 3 and 6 | 
| Change From Baseline in Number of Hours Per Day as Assessed Using RA-HCRU at Months 12, 18, and 24 | RA-HCRU assessed HC usage during previous 3 months for direct or indirect medical cost domains. Any RA or non-RA related number of hours spent per day for home HC services, chores done by housekeeper, chores done by family or friends, work done and work missed were reported. | Months 12, 18, and 24 | 
| Change From Baseline in Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU | Work performance of participants on number of days bothered was based on a 0 to 10-point scale, where higher score indicated lower work performance. | Months 3, 6, 12, 18, and 24 | 
| Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline and Months 1, 2, and 3 | Participant-rated 12 item questionnaire to assess constructs of sleep over past week. 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes or no). 9-item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except Adequacy, Optimal, Quantity of sleep, higher cores=more impairment. Scores transformed (actual raw score [RS] minus lowest possible score divided by possible RS range*100); total score range: 0-100, higher score=more intensity of attribute. | Baseline and Months 1, 2, and 3 | 
| Percentage of Participants With Optimal Sleep Assessed Using MOS-SS | MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Number of participants with optimal sleep are reported | Months 1, 2, 3, 6, 12, 18, and 24 | 
| Medical Outcomes Study Sleep Scale (MOS-SS) at Months 6, 12, 18, and 24 | Participant-rated 12 item questionnaire to assess constructs of sleep over past week. 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes or no). 9-item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except Adequacy, Optimal, Quantity of sleep, higher cores=more impairment. Scores transformed (actual raw score [RS] minus lowest possible score divided by possible RS range*100); total score range: 0-100, higher score=more intensity of attribute. | Months 6, 12, 18, and 24 | 
| Change From Baseline in MOS-SS at Months 1, 2, and 3 | Participant-rated 12 item questionnaire to assess constructs of sleep over past week. 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes or no). 9-item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except Adequacy, Optimal, Quantity of sleep, higher cores=more impairment. Scores transformed (actual raw score [RS] minus lowest possible score divided by possible RS range*100); total score range: 0-100, higher score=more intensity of attribute. | Months 1, 2, and 3 | 
| Change From Baseline in MOS-SS at Months 6, 12, 18, and 24 | Participant-rated 12 item questionnaire to assess constructs of sleep over past week. 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes or no). 9-item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except Adequacy, Optimal, Quantity of sleep, higher cores=more impairment. Scores transformed (actual raw score [RS] minus lowest possible score divided by possible RS range*100); total score range: 0-100, higher score=more intensity of attribute. | Months 6, 12, 18, and 24 | 
| Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale | FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status | Baseline and Months 1, 2, 3, 6, 12, 18, and 24 | 
| Change From Baseline in FACIT-Fatigue Scale | FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status | Months 1, 2, 3, 6, 12, 18, and 24 | 
| Change From Baseline in Heart Rate |  | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 
| Change From Baseline in Temperature |  | Months 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral JAK inhibitor, MTX, DMARD, clinical trial, joint diseases, autoimmune diseases, anti-Inflammatory agents, rheumatic diseases