A Study Comparing 2 Doses Of CP-690,550 Vs. Placebo For The Treatment Of Rheumatoid Arthritis In Patients On Other Background Arthritis Medications

Phase 3, Randomized, Double Blind, Placebo Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background DMARDS

This Phase 3 study is intended to provide evidence that CP-690,550 dosed 5 mg BID and 10 mg BID is safe and effective when used in combination with a variety of traditional disease modifying antirheumatic drugs in adult patients with rheumatoid arthritis. It is intended to confirm the benefits of CP-690,550 in improving signs and symptoms and physical function that were observed in the Phase 2 rheumatoid arthritis studies.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: CP-690,550; Drug: CP-690,550; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 795
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Campsie, New South Wales, Australia, 2194
      • Pfizer Investigational Site
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Pfizer Investigational Site
    • Maroochydore, Queensland, Australia, 4558
      • Pfizer Investigational Site
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Pfizer Investigational Site
  • Victoria
    • Malvern East, Victoria, Australia, 3145
      • Pfizer Investigational Site
  • Western Australia
    • Shenton Park, Western Australia, Australia, 6008
      • Pfizer Investigational Site
• Chile
  • Vina del Mar, Chile, 2570017
    • Pfizer Investigational Site
  • RM
    • Santiago, RM, Chile, 7510186
      • Pfizer Investigational Site
    • Santiago, RM, Chile, 8360156
      • Pfizer Investigational Site
  • Santiago, RM
    • Providencia, Santiago, RM, Chile, 7530206
      • Pfizer Investigational Site
  • V Region
    • Vina del Mar, V Region, Chile, 2570017
      • Pfizer Investigational Site
• China
  • Beijing, China, 100853
    • Pfizer Investigational Site
  • Beijing, China, 100020
    • Pfizer Investigational Site
  • Beijing, China, 100044
    • Pfizer Investigational Site
  • Shanghai, China, 200001
    • Pfizer Investigational Site
  • Shanghai, China, 200433
    • Pfizer Investigational Site
  • Shanghai, China, 200003
    • Pfizer Investigational Site
  • Tianjin, China, 300052
    • Pfizer Investigational Site
  • Anhui
    • Hefei, Anhui, China, 230022
      • Pfizer Investigational Site
    • Hefei, Anhui, China, 230001
      • Pfizer Investigational Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Pfizer Investigational Site
    • Guangzhou, Guangdong, China, 510260
      • Pfizer Investigational Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Pfizer Investigational Site
  • Hunan
    • Changsha, Hunan, China, 410008
      • Pfizer Investigational Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Pfizer Investigational Site
    • Suzhou, Jiangsu, China, 215006
      • Pfizer Investigational Site
  • Shandong
    • Jinan, Shandong, China, 250012
      • Pfizer Investigational Site
    • Qingdao, Shandong, China, 266011
      • Pfizer Investigational Site
  • Shanxi
    • Xi'an, Shanxi, China, 710032
      • Pfizer Investigational Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Pfizer Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Pfizer Investigational Site
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 0000
      • Pfizer Investigational Site
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Pfizer Investigational Site
  • Santander
    • Bucaramanga, Santander, Colombia
      • Pfizer Investigational Site
• Croatia
  • Opatija, Croatia, 51410
    • Pfizer Investigational Site
  • Zagreb, Croatia, 10000
    • Pfizer Investigational Site
• Denmark
  • Frederiksberg, Denmark, 2000
    • Pfizer Investigational Site
• Finland
  • Helsinki, Finland, 00120
    • Pfizer Investigational Site
  • Hyvinkaa, Finland, 05800
    • Pfizer Investigational Site
  • Tampere, Finland, 33520
    • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 14059
    • Pfizer Investigational Site
  • Dresden, Germany, 01067
    • Pfizer Investigational Site
  • Hamburg, Germany, 22081
    • Pfizer Investigational Site
  • Leipzig, Germany, 04103
    • Pfizer Investigational Site
  • Nuernberg, Germany, 90429
    • Pfizer Investigational Site
  • Rheine, Germany, 48431
    • Pfizer Investigational Site
• Greece
  • Maroussi Athens, Greece, 15126
    • Pfizer Investigational Site
• Malaysia
  • Negeri Sembilan
    • Seremban, Negeri Sembilan, Malaysia, 70300
      • Pfizer Investigational Site
  • Selangor
    • Batu Caves, Selangor, Malaysia, 68100
      • Pfizer Investigational Site
    • Subang Jaya, Selangor, Malaysia, 47500
      • Pfizer Investigational Site
  • Wilayah Persekutuan
    • Putrajaya, Wilayah Persekutuan, Malaysia, 62250
      • Pfizer Investigational Site
• Mexico
  • Coahuila
    • Torreon, Coahuila, Mexico, 27000
      • Pfizer Investigational Site
  • Michoacan
    • Morelia, Michoacan, Mexico, 58249
      • Pfizer Investigational Site
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62270
      • Pfizer Investigational Site
  • Queretaro
    • Mexico, Queretaro, Mexico, 76178
      • Pfizer Investigational Site
  • Yucatan
    • Merida, Yucatan, Mexico, 97000
      • Pfizer Investigational Site
• Poland
  • Bialystok, Poland, 15-337
    • Pfizer Investigational Site
  • Bialystok, Poland, 15-461
    • Pfizer Investigational Site
  • Koscian, Poland, 64-000
    • Pfizer Investigational Site
  • Poznan, Poland, 60-773
    • Pfizer Investigational Site
  • Torun, Poland, 87-100
    • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 115093
    • Pfizer Investigational Site
  • Moscow, Russian Federation, 115446
    • Pfizer Investigational Site
  • Petrozavodsk, Russian Federation, 185019
    • Pfizer Investigational Site
• Slovakia
  • Nove Zamky, Slovakia, 94001
    • Pfizer Investigational Site
  • Poprad, Slovakia, 058 01
    • Pfizer Investigational Site
  • Povazska Bystrica, Slovakia, 017 01
    • Pfizer Investigational Site
  • Rimavska Sobota, Slovakia, 979 01
    • Pfizer Investigational Site
  • Senica, Slovakia, 905 01
    • Pfizer Investigational Site
  • Zilina, Slovakia, 010 01
    • Pfizer Investigational Site
• Spain
  • A Coruña, Spain, 15006
    • Pfizer Investigational Site
  • Madrid, Spain, 28046
    • Pfizer Investigational Site
  • Malaga, Spain, 29009
    • Pfizer Investigational Site
  • Sevilla, Spain, 41013
    • Pfizer Investigational Site
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15705
      • Pfizer Investigational Site
• Sweden
  • Falun, Sweden, 791 82
    • Pfizer Investigational Site
  • Goteborg, Sweden, 413 46
    • Pfizer Investigational Site
  • Uppsala, Sweden, 751 85
    • Pfizer Investigational Site
• Thailand
  • Bangkok
    • Rajathevee, Bangkok, Thailand, 10400
      • Pfizer Investigational Site
  • Chiang Mai
    • Amphoe Muang, Chiang Mai, Thailand, 50200
      • Pfizer Investigational Site
  • Khonkaen
    • Muang District, Khonkaen, Thailand, 40002
      • Pfizer Investigational Site
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Pfizer Investigational Site
  • Merseyside
    • Wirral, Merseyside, United Kingdom, CH49 5PE
      • Pfizer Investigational Site
  • Staffs
    • Cannock, Staffs, United Kingdom, WS11 2XY
      • Pfizer Investigational Site
  • West Midlands
    • Solihull, West Midlands, United Kingdom, B91 2JL
      • Pfizer Investigational Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Pfizer Investigational Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Pfizer Investigational Site
  • California
    • Palo Alto, California, United States, 94304
      • Pfizer Investigational Site
    • Stanford, California, United States, 94305
      • Pfizer Investigational Site
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Pfizer Investigational Site
    • Denver, Colorado, United States, 80206
      • Pfizer Investigational Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Pfizer Investigational Site
    • Hamden, Connecticut, United States, 06518
      • Pfizer Investigational Site
    • Trumbull, Connecticut, United States, 06611
      • Pfizer Investigational Site
  • Florida
    • New Port Richey, Florida, United States, 34652
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34474
      • Pfizer Investigational Site
    • Plantation, Florida, United States, 33324
      • Pfizer Investigational Site
    • Port Richey, Florida, United States, 34668
      • Pfizer Investigational Site
    • Tamarac, Florida, United States, 33321
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33613
      • Pfizer Investigational Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Pfizer Investigational Site
    • Marietta, Georgia, United States, 30060
      • Pfizer Investigational Site
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Pfizer Investigational Site
    • Oakbrook Terrace, Illinois, United States, 60181
      • Pfizer Investigational Site
    • Rockford, Illinois, United States, 61103-3692
      • Pfizer Investigational Site
    • Springfield, Illinois, United States, 62702
      • Pfizer Investigational Site
    • Springfield, Illinois, United States, 62703
      • Pfizer Investigational Site
    • Vernon Hills, Illinois, United States, 60061
      • Pfizer Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Pfizer Investigational Site
    • Indianapolis, Indiana, United States, 46227
      • Pfizer Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Pfizer Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40505
      • Pfizer Investigational Site
  • Massachusetts
    • Leominster, Massachusetts, United States, 01453
      • Pfizer Investigational Site
    • Worcester, Massachusetts, United States, 01605
      • Pfizer Investigational Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Pfizer Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Pfizer Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Pfizer Investigational Site
    • Orchard Park, New York, United States, 14127
      • Pfizer Investigational Site
    • Rochester, New York, United States, 14618
      • Pfizer Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Pfizer Investigational Site
    • Charlotte, North Carolina, United States, 28210
      • Pfizer Investigational Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Pfizer Investigational Site
    • Wyomissing, Pennsylvania, United States, 19610
      • Pfizer Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Pfizer Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Pfizer Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75235
      • Pfizer Investigational Site
  • Washington
    • Seattle, Washington, United States, 98133
      • Pfizer Investigational Site
    • Tacoma, Washington, United States, 98405
      • Pfizer Investigational Site
    • Tacoma, Washington, United States, 98405-2308
      • Pfizer Investigational Site
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Pfizer Investigational Site
• Venezuela
  • DC/ Municipio Libertados
    • Caracas, DC/ Municipio Libertados, Venezuela, 1040-A
      • Pfizer Investigational Site
  • Distrito Capital
    • Caracas, Distrito Capital, Venezuela, 1010
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has a diagnosis of Rheumatoid Arthritis based on the American College of Rheumatology (ACR) 1987 Revised Criteria.
• The patient has active disease as defined by both >=4 tender or painful joints on motion and >= 4 joints swollen; and either an erythrocyte sedimentation rate (ESR) > 28 mm or a C-reactive protein (CRP) concentration > 7 mg/dL.
• Patient had an inadequate response to at least one disease modifying antirheumatic drug (traditional or biologic) due to lack of efficacy or toxicity.
• Patient must remain on at least one background traditional disease modifying antirheumatic drug.
• No evidence of inadequately treated latent or active infection with Mycobacterium tuberculosis.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active 10 mg	Drug: CP-690,550; Film coated tablet, 5 mg PO BID, 1 year; Drug: CP-690,550; Film coated tablet, 10 mg PO BID, 1 year
Experimental: Active 5 mg	Drug: CP-690,550; Film coated tablet, 5 mg PO BID, 1 year; Drug: CP-690,550; Film coated tablet, 10 mg PO BID, 1 year
Placebo Comparator: Placebo Sequence 1; Placebo non-responders advance to 5 mg CP-690,550 at Month 3 visit. All patients in this treatment arm advance to 5 mg CP-690,550 at Month 6 visit.	Drug: Placebo; Film coated tablet, 1 tablet PO BID, 3-6 months
Placebo Comparator: Placebo Sequence 2; Placebo non-responders advance to 10 mg CP-690,550 at Month 3 visit. All patients in this treatment arm advance to 10 mg CP-690,550 at Month 6 visit.	Drug: Placebo; Film coated tablet, 1 tablet PO BID, 3-6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Month 3	HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities:dress/groom;arise;eat; walk;reach;grip; 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;3=unable to do. 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. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.	Baseline, Month 3
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 6	ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joint count (TJC); >= 20% improvement in swollen joint count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant 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). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.	Month 6
Percentage of Participants Achieving Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])Less Than 2.6 at Month 6	DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeters/hour[mm/hour]) and patient's global assessment (PtGA) of disease activity(participant rated arthritis activity assessment). Total score range:0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (<=)3.2 implied low disease activity, greater than (>)3.2 to 5.1 implied moderate to high disease activity, less than (<)2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Month 9 and 12	DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint 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, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.	Month 9, 12
Patient Assessment of Arthritis Pain at Month 9 and 12	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.	Month 9, 12
Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Baseline, Month 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, Month 3, 6
Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Month 12	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.	Month 12
36-Item Short-Form Health Survey (SF-36) at Baseline, Month 1, 3 and 6	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, Month 1, 3, 6
Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Month 1, 3 and 6	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 scores=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, Month 1, 3, 6
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Month 1, 3 and 6	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.	Baseline, Month 1, 3, 6
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Baseline, Month 1, 3, and 6	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, Month 1, 3, 6
Euro Quality of Life (EQ-5D)- Health State Profile Utility Score at Baseline, Month 3 and 6	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, Month 3, 6
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) at Week 2, Month 1, 2, 3, 4.5 and 6	ACR20 response: >=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 assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP.	Week 2, Month 1, 2, 3, 4.5, 6
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) at Month 9 and 12	ACR20 response: >=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 assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP.	Month 9, 12
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) at Week 2, Month 1, 2, 3, 4.5 and 6	ACR50 response: >=50% improvement in tender joint count; >=50% improvement in swollen joint count; and >=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP.	Week 2, Month 1, 2, 3, 4.5, 6
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) at Month 9 and 12	ACR50 response: >=50% improvement in tender joint count; >=50% improvement in swollen joint count; and >=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP.	Month 9, 12
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) at Week 2, Month 1, 2, 3, 4.5 and 6	ACR70 response: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP.	Week 2, Month 1, 2, 3, 4.5, 6
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) at Month 9 and 12	ACR70 response: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP.	Month 9, 12
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Baseline, Week 2, Month 1, 2, 3, 4.5 and 6	DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint 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, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.	Week 2, Month 1, 2, 3, 4.5, 6
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Baseline, Month 3 and 6	DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, ESR (mm/hour) and PGA of disease activity (participant rated arthritis activity assessment with transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.	Baseline, Month 3, 6
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Month 12	DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, ESR (mm/hour) and PGA of disease activity (participant rated arthritis activity assessment with transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.	Month 12
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])	DAS28-4 (CRP) was calculated from SJC and TJC using the 28 joints count, CRP [mg/L] and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 [CRP] <=3.2 implied low disease activity, DAS28-4 [CRP] >3.2 to 5.1 implied moderate to high disease activity and DAS28 <2.6 implied remission.	Baseline, Week 2, Month 1, 2, 3, 4.5, 6, 9, 12
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])	DAS28-3 (ESR) was calculated from the number of SJC and TJC using the 28 joints count and ESR (mm/hr). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (ESR) <=3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.	Baseline, Month 3, 6, 12
Health Assessment Questionnaire Disability Index (HAQ-DI) at Baseline, Week 2, Month 1, 2, 3, 4.5 and 6	HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3=extreme difficulty.	Baseline, Week 2, Month 1, 2, 3, 4.5, 6
Health Assessment Questionnaire Disability Index (HAQ-DI) at Month 9 and 12	HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0=least difficulty and 3=extreme difficulty.	Month 9, Month 12
Patient Assessment of Arthritis Pain at Baseline, Week 2, Month 1, 2, 3, 4.5 and 6	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, Week 2, Month 1, 2, 3, 4.5, 6
Patient Global Assessment (PtGA) of Arthritis Pain at Baseline, Week 2, Month 1, 2, 3, 4.5 and 6	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, Week 2, Month 1, 2, 3, 4.5, 6
Patient Global Assessment (PtGA) of Arthritis Pain at Month 9 and 12	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.	Month 9, 12
Physician Global Assessment (PGA) of Arthritis Pain at Baseline, Week 2, Month 1, 2, 3, 4.5 and 6	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, Week 2, Month 1, 2, 3, 4.5, 6
Physician Global Assessment (PGA) of Arthritis at Month 9 and 12	Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	Month 9, 12
36-Item Short-Form Health Survey (SF-36) at Month 9 and 12	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.	Month 9, 12
Medical Outcome Study (MOS) Sleep Scale at Month 12	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 scores=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.	Month 12
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Month 12	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.	Month 12
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Month 12	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.	Month 12
Euro Quality of Life (EQ-5D)- Health State Profile Utility Score at Month 12	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.	Month 12
Work Limitations Questionnaire (WLQ) Score at Baseline, Month 3 and 6	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, Month 3, 6
Work Limitations Questionnaire (WLQ) Score at Month 12	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]).	Month 12
Work Productivity and Healthcare Resource Utilization (HCRU) at Baseline, Month 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, over-night 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, Month 3, 6
Work Productivity and Healthcare Resource Utilization (HCRU) at Month 12	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, over-night 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.	Month 12
Number of Days as Assessed Using RA-HCRU at Baseline, Month 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, Month 3, 6
Number of Days as Assessed Using RA-HCRU at Month 12	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.	Month 12
Number of Hours Per Day as Assessed RA-HCRU at Baseline, Month 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 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, Month 3, 6
Number of Hours Per Day as Assessed RA-HCRU at Month 12	RA-HCRU assessed healthcare 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.	Month 12
Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Baseline, Month 3 and 6	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, Month 3, 6
Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Month 12	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.	Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Greater Than 1 Day Sequential Decrease in Pain From Baseline for Patient Global Assessment of Arthritis	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.	2 weeks
Time to First Greater Than 1 Day Sequential Decrease in Pain From Baseline for 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.	2 weeks

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2020 Oct 10;:
• Dikranian A, Gold D, Bessette L, Nash P, Azevedo VF, Wang L, Woolcott J, Shapiro AB, Szumski A, Fleishaker D, Wollenhaupt J. Frequency and Duration of Early Non-serious Adverse Events in Patients with Rheumatoid Arthritis and Psoriatic Arthritis Treated with Tofacitinib. Rheumatol Ther. 2022 Apr;9(2):411-433. doi: 10.1007/s40744-021-00405-w. Epub 2021 Dec 17.
• Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
• Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
• Charles-Schoeman C, Burmester G, Nash P, Zerbini CA, Soma K, Kwok K, Hendrikx T, Bananis E, Fleischmann R. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14. Erratum In: Ann Rheum Dis. 2017 Mar;76(3):611.
• Dikranian AH, Gonzalez-Gay MA, Wellborne F, Alvaro-Gracia JM, Takiya L, Stockert L, Paulissen J, Shi H, Tatulych S, Curtis JR. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: an analysis of pooled data from phase 3 studies. RMD Open. 2022 May;8(1):e002103. doi: 10.1136/rmdopen-2021-002103.
• Bartlett SJ, Bingham CO, van Vollenhoven R, Murray C, Gruben D, Gold DA, Cella D. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials. Arthritis Res Ther. 2022 Apr 5;24(1):83. doi: 10.1186/s13075-022-02724-x.
• Strand V, Kaine J, Alten R, Wallenstein G, Diehl A, Shi H, Germino R, Murray CW. Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib. Arthritis Res Ther. 2020 Oct 15;22(1):243. doi: 10.1186/s13075-020-02324-7.
• Kivitz AJ, Cohen S, Keystone E, van Vollenhoven RF, Haraoui B, Kaine J, Fan H, Connell CA, Bananis E, Takiya L, Fleischmann R. A pooled analysis of the safety of tofacitinib as monotherapy or in combination with background conventional synthetic disease-modifying antirheumatic drugs in a Phase 3 rheumatoid arthritis population. Semin Arthritis Rheum. 2018 Dec;48(3):406-415. doi: 10.1016/j.semarthrit.2018.07.006. Epub 2018 Jul 19.
• Hall S, Nash P, Rischmueller M, Bossingham D, Bird P, Cook N, Witcombe D, Soma K, Kwok K, Thirunavukkarasu K. Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Australian Rheumatoid Arthritis Population. Rheumatol Ther. 2018 Dec;5(2):383-401. doi: 10.1007/s40744-018-0118-2. Epub 2018 Jun 11.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.
• Li ZG, Liu Y, Xu HJ, Chen ZW, Bao CD, Gu JR, Zhao DB, An Y, Hwang LJ, Wang L, Kremer J, Wu QZ. Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis. Chin Med J (Engl). 2018 Nov 20;131(22):2683-2692. doi: 10.4103/0366-6999.245157.
• Strand V, Kremer JM, Gruben D, Krishnaswami S, Zwillich SH, Wallenstein GV. Tofacitinib in Combination With Conventional Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis: Patient-Reported Outcomes From a Phase III Randomized Controlled Trial. Arthritis Care Res (Hoboken). 2017 Apr;69(4):592-598. doi: 10.1002/acr.23004.
• Kremer J, Li ZG, Hall S, Fleischmann R, Genovese M, Martin-Mola E, Isaacs JD, Gruben D, Wallenstein G, Krishnaswami S, Zwillich SH, Koncz T, Riese R, Bradley J. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013 Aug 20;159(4):253-61. doi: 10.7326/0003-4819-159-4-201308200-00006.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: March 3, 2009
• First Submitted That Met QC Criteria: March 3, 2009
• First Posted (Estimate): March 5, 2009

Study Record Updates

• Last Update Posted (Estimate): January 10, 2013
• Last Update Submitted That Met QC Criteria: December 6, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Arthritis; Rheumatoid; Clinical Trial; Antirheumatic Agents
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921046