A Phase 3 Study Comparing 2 Doses Of CP-690,550 And The Active Comparator, Humira (Adalimumab) Vs. Placebo For Treatment Of Rheumatoid Arthritis

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

This is a comparative study of CP 690,550, Humira (adalimumab) and placebo on background methotrexate in patients with Rheumatoid Arthritis. The study is intended to provide evidence of the efficacy and safety of CP 690,550 when dosed 5 mg and 10 mg twice a day on background methotrexate in adult patients with moderate to severe 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 Rheumatoid Arthritis. An active comparator, adalimumab, is also included.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 717
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Pfizer Investigational Site
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Pfizer Investigational Site
    • Maroochydore, Queensland, Australia, 4558
      • Pfizer Investigational Site
  • Victoria
    • Malvern East, Victoria, Australia, 3145
      • Pfizer Investigational Site
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Pfizer Investigational Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Pfizer Investigational Site
  • Plovdiv, Bulgaria, 4002
    • Pfizer Investigational Site
  • Plovdiv, Bulgaria, 4000
    • Pfizer Investigational Site
  • Sevlievo, Bulgaria, 5400
    • Pfizer Investigational Site
  • Sofia, Bulgaria, 1606
    • Pfizer Investigational Site
  • Sofia, Bulgaria, 1709
    • Pfizer Investigational Site
• Canada
  • Quebec, Canada, G1W 4R4
    • Pfizer Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L7
      • Pfizer Investigational Site
  • Nova Scotia
    • Lunenburg, Nova Scotia, Canada, B0J 2C0
      • Pfizer Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • Pfizer Investigational Site
    • Mississauga, Ontario, Canada, L5M 2V8
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M5T 2S8
      • Pfizer Investigational Site
  • Quebec
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • Pfizer Investigational Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Pfizer Investigational Site
• Chile
  • 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
  • VI Region
    • Rancagua, VI Region, Chile, 2841959
      • Pfizer Investigational Site
• Costa Rica
  • Cartago, Costa Rica
    • Pfizer Investigational Site
  • San Jose, Costa Rica
    • Pfizer Investigational Site
  • San Jose, Costa Rica, 00
    • Pfizer Investigational Site
• Croatia
  • Osijek, Croatia, 31000
    • Pfizer Investigational Site
  • Split, Croatia, 21000
    • Pfizer Investigational Site
  • Zagreb, Croatia, 10000
    • Pfizer Investigational Site
• Czech Republic
  • Brno, Czech Republic, 656 91
    • Pfizer Investigational Site
  • Brno, Czech Republic, 65691
    • Pfizer Investigational Site
  • Brno, Czech Republic, 60200
    • Pfizer Investigational Site
  • Brno - Zidenice, Czech Republic, 615 00
    • Pfizer Investigational Site
  • Hlucin, Czech Republic, 748 01
    • Pfizer Investigational Site
  • Pardubice, Czech Republic, 530 02
    • Pfizer Investigational Site
  • Praha 11, Czech Republic, 14800
    • Pfizer Investigational Site
  • Praha 11 - Chodov, Czech Republic, 148 00
    • Pfizer Investigational Site
  • Praha 2, Czech Republic, 128 50
    • Pfizer Investigational Site
  • Praha 4, Czech Republic, 140 00
    • Pfizer Investigational Site
  • Zlin, Czech Republic, 760 01
    • Pfizer Investigational Site
• Denmark
  • Frederiksberg, Denmark, 2000
    • Pfizer Investigational Site
  • Randers NOE, Denmark, 8930
    • Pfizer Investigational Site
• Dominican Republic
  • Santo Domingo, Dominican Republic, 00000
    • Pfizer Investigational Site
• Finland
  • Hyvinkaa, Finland, 05800
    • Pfizer Investigational Site
• Germany
  • Aachen, Germany, 52064
    • Pfizer Investigational Site
  • Berlin, Germany, 14059
    • Pfizer Investigational Site
  • Frankfurt am Main, Germany, 60590
    • Pfizer Investigational Site
  • Halle, Germany, 06108
    • Pfizer Investigational Site
  • Halle, Germany, 06128
    • Pfizer Investigational Site
  • Herne, Germany, 44652
    • Pfizer Investigational Site
  • Ratingen, Germany, 40882
    • Pfizer Investigational Site
  • Wuerzburg, Germany, 97080
    • Pfizer Investigational Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-718
    • Pfizer Investigational Site
  • Gwangju, Korea, Republic of, 501-757
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 133-792
    • Pfizer Investigational Site
• Mexico
  • DF
    • Mexico, DF, Mexico, 10700
      • Pfizer Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44620
      • Pfizer Investigational Site
  • Michoacan
    • Morelia, Michoacan, Mexico, 58249
      • Pfizer Investigational Site
  • SLP
    • San Luis Potosi, SLP, Mexico, 78240
      • Pfizer Investigational Site
• Philippines
  • Cebu City, Philippines, 6000
    • Pfizer Investigational Site
  • Batangas
    • Lipa City, Batangas, Philippines, 4217
      • Pfizer Investigational Site
  • Pampanga
    • Angeles City, Pampanga, Philippines, 2009
      • Pfizer Investigational Site
• Poland
  • Bialystok, Poland, 15-337
    • Pfizer Investigational Site
  • Cieszyn, Poland, 43-400
    • Pfizer Investigational Site
  • Koscian, Poland, 64-000
    • Pfizer Investigational Site
  • Krakow, Poland, 31-501
    • Pfizer Investigational Site
  • Sopot, Poland, 81-759
    • Pfizer Investigational Site
  • Torun, Poland, 87-100
    • Pfizer Investigational Site
  • Warszawa, Poland, 02-118
    • Pfizer Investigational Site
• Slovakia
  • Bratislava, Slovakia, 82606
    • Pfizer Investigational Site
  • Dunajska Streda, Slovakia, 92901
    • Pfizer Investigational Site
  • Kosice, Slovakia, 040 01
    • Pfizer Investigational Site
  • Nove Zamky, Slovakia, 94001
    • Pfizer Investigational Site
  • Povazska Dystrica, Slovakia, 017 01
    • Pfizer Investigational Site
  • Zilina, Slovakia, 010 01
    • Pfizer Investigational Site
• Spain
  • A Coruña, Spain, 15006
    • Pfizer Investigational Site
  • Madrid, Spain, 28041
    • Pfizer Investigational Site
  • Sevilla, Spain, 41009
    • Pfizer Investigational Site
  • Valencia, Spain, 46026
    • Pfizer Investigational Site
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15705
      • Pfizer Investigational Site
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36200
      • Pfizer Investigational Site
• Thailand
  • Bangkok
    • Rajathevee, Bangkok, Thailand, 10400
      • Pfizer Investigational Site
  • Chiang Mai
    • Amphoe Muang, Chiang Mai, Thailand, 50200
      • Pfizer Investigational Site
• United Kingdom
  • Dudley, West Midlands, United Kingdom, DY1 2HQ
    • Pfizer Investigational Site
  • Merseyside
    • Wirral, Merseyside, United Kingdom, CH49 5PE
      • Pfizer Investigational Site
  • Staffs
    • Cannock, Staffs, United Kingdom, WS11 2XY
      • Pfizer Investigational Site
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Pfizer Investigational Site
    • Glendale, Arizona, United States, 85304
      • Pfizer Investigational Site
    • Mesa, Arizona, United States, 85202
      • Pfizer Investigational Site
    • Paradise Valley, Arizona, United States, 85253
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85037
      • Pfizer Investigational Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Pfizer Investigational Site
  • California
    • Fair Oaks, California, United States, 95628
      • Pfizer Investigational Site
    • San Diego, California, United States, 92108
      • Pfizer Investigational Site
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Pfizer Investigational Site
  • Florida
    • Largo, Florida, United States, 33777
      • Pfizer Investigational Site
    • Naples, Florida, United States, 34102
      • Pfizer Investigational Site
    • Palm Harbor, Florida, United States, 34684
      • Pfizer Investigational Site
    • Pinellas Park, Florida, United States, 33782
      • Pfizer Investigational Site
    • Plantation, Florida, United States, 33324
      • Pfizer Investigational Site
    • St. Petersburg, Florida, United States, 33710
      • 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
    • Rockford, Illinois, United States, 61107
      • Pfizer Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Pfizer Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Pfizer Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Pfizer Investigational Site
    • Lexington, Kentucky, United States, 40515
      • Pfizer Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Pfizer Investigational Site
  • Massachusetts
    • Haverhill, Massachusetts, United States, 01830
      • Pfizer Investigational Site
    • Worcester, Massachusetts, United States, 01610
      • Pfizer Investigational Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pfizer Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Pfizer Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75231
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77034
      • Pfizer Investigational Site
    • Lubbock, Texas, United States, 79424
      • Pfizer Investigational Site
    • Mesquite, Texas, United States, 75150
      • Pfizer Investigational Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Pfizer Investigational Site
    • Seattle, Washington, United States, 98122
      • Pfizer Investigational Site
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria.
• The patient must have had an inadequate response to methotrexate and have active disease, as defined by both: ≥6 joints tender or painful on motion; and ≥6 joints swollen; and fulfills 1 of the following 2 criteria at Screening: 1.ESR (Westergren method) >28 mm in the local laboratory. 2. CRP >7 mg/L in the central laboratory.
• No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis.
• The patient must have been on a stable dose of 7.5 mg to 25 mg weekly of methotrexate and washed out of all other DMARDs.

Exclusion Criteria:

• Blood dyscrasias including confirmed: 1. Hemoglobin <9 g/dL or Hematocrit <30%; 2. White blood cell count <3,000 cu.mm. Absolute neutrophil count <1,200 cu.mm; 4. Platelet count <100,000/L
• History of any other autoimmune rheumatic 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
• Patients who have failed any TNFi for either lack of efficacy or a TNFi mechanism related adverse event.
• Patients who have previously received adalimumab therapy for any reason.
• Patients who are contraindicated for treatment with adalimumab in accordance with the approved local label.
• Patients meeting the New York Heart Association Class III and Class IV Congestive Heart failure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5mg	Drug: CP 690,550; tablets 5 mg BID PO plus q2 week placebo SC injections for 12 months
Experimental: 10 mg	Drug: CP-690,550; tablets 10 mg BID PO plus q2 week placebo SC injections for 12 months
Placebo Comparator: Placebo Sequence 1	Other: Placebo; placebo tablets BID PO advance to 5mg CP 690,550 BID at Month 3 or 6 visit plus q2 week placebo SC injections for 12 months; Other: Placebo; tablets BID PO advance tablets to10mg CP 690,550 BID at Month 3 or 6 visit plus q2 week placebo SC injections for 12 months
Placebo Comparator: Placebo Sequence 2	Other: Placebo; placebo tablets BID PO advance to 5mg CP 690,550 BID at Month 3 or 6 visit plus q2 week placebo SC injections for 12 months; Other: Placebo; tablets BID PO advance tablets to10mg CP 690,550 BID at Month 3 or 6 visit plus q2 week placebo SC injections for 12 months
Active Comparator: adalimumab	Biological: Biologic TNFi; placebo tablets BID PO plus adalimumab 40 mg q2 week SC injections for 12 months; Other Names: Humira (Adalimumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 6	ACR20 response: greater than or equal to (>=) 20% 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
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) 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 With 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) calculated from SJC and TJC using 28-joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (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) less than or equal to (<=) 3.2 implied low disease activity and > 3.2 to 5.1 implied moderate to high disease activity, and < 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
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 1 and 3	ACR20 response: >=20% improvement in TJC; >= 20% improvement in 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 HAQ); and CRP.	Month 1, 3
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response 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 the HAQ); and CRP.	Month 9, 12
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 1, 3 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 the HAQ); and CRP.	Month 1, 3, 6
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response 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 the HAQ); and CRP.	Month 9, 12
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 1, 3 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 the HAQ); and CRP.	Month 1, 3, 6
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response 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 the HAQ); and CRP.	Month 9, 12
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Baseline, Month 1, 3 and 6	DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint count and CRP (milligram per liter [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.	Baseline, Month 1, 3, 6
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
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Baseline, Month 1, 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 1, 3, 6
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Month 9 and 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 9, 12
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])	DAS28-4 [CRP] calculated from SJC and TJC using 28 joint count, CRP (mg/L) 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 (CRP) =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.	Baseline, Month 1, 3, 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 SJC and TJC using 28 joint count and ESR (mm/hour). 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 1, 3, 6, 9, 12
Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 1, 3 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; 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.	Month 1, 3, 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; 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.	Month 9, 12
Patient Assessment of Arthritis Pain at Baseline, Month 1, 3 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, Month 1, 3, 6
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
Patient Global Assessment (PtGA) of Arthritis Pain at Baseline, Month 1, 3 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 mm = very well and 100 mm = very poorly.	Baseline, Month 1, 3, 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 mm = very well and 100 mm = very poorly.	Month 9, 12
Physician Global Assessment (PGA) of Arthritis Pain at Baseline, Month 1, 3 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, Month 1, 3, 6
Physician Global Assessment (PGA) of Arthritis Pain 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 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 was reported as 2 summary scores; Physical Component Score and Mental Component Score. Total score range for the summary scores = 0-100 where higher scores represented higher level of functioning.	Baseline, Month 1, 3, 6
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 was reported as 2 summary scores; Physical Component Score and Mental Component Score. Total score range for the summary scores = 0-100 where higher scores represented higher level of functioning.	Month 9, 12
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)-Fatigue Scale at Baseline, Month 1, 3 and 6	FACIT-Fatigue scale 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
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)-Fatigue Scale at Month 12	FACIT-Fatigue scale 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
Medical Outcomes Study-Sleep Scale (MOS-SS) at Baseline, Month 1, 3 and 6	Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 sub scales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range:0-100); sleep quantity (Qua)(range:0-24), and optimal (Opt) sleep (yes: 1, no: 0) and nine item index measures of sleep disturbance were constructed to provide composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range* 100); total score range: 0 to 100; higher score = greater intensity of attribute.	Baseline, Month 1, 3, 6
Medical Outcomes Study-Sleep Scale (MOS-SS) at Month 12	Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 sub scales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range:0-100); sleep quantity (Qua)(range:0-24), and optimal (Opt) sleep (yes: 1, no: 0) and nine item index measures of sleep disturbance were constructed to provide composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range* 100); total score range: 0 to 100; higher score = greater intensity of attribute.	Month 12
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
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
Euro Quality of Life-5 Dimension (EQ-5D) Health State Profile Utility Score at Baseline, Month 1, 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 1, 3, 6
Euro Quality of Life-5 Dimension (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 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: 5-items Time Management scale (TMS); 6-items Physical Demands scale (PDS); 9-items Mental-Interpersonal Demands Scale (MIDS); 5-items Output Demands scale (ODS). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index (WLI), 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 3, 6
Work Limitations Questionnaire (WLQ) Score at Baseline and 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: 5-items Time Management scale (TMS); 6-items Physical Demands scale (PDS); 9-items Mental-Interpersonal Demands Scale (MIDS); 5-items Output Demands scale (ODS). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index (WLI), 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 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: any RA/non-RA related medical/non-medical (NM) practitioner visit, nursing home, hospital, surgery, emergency room (ER) treatment, diagnostic tests, over-night stay, home healthcare (HC) 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 indicated higher medical cost.	Baseline, Month 3, 6
Work Productivity and Healthcare Resource Utilization (HCRU) at Month 12	RA-HCRU assessed healthcare usage during last 3 months for direct, indirect medical cost domains. Direct cost: visit to doctor, NM practitioner, nursing home, hospital, surgery, ER treatment, diagnostic tests, over-night stay, home HC services, and 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 indicated higher medical cost.	Month 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
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, hours affected per day and average number of hours missed work per day 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, hours affected per day and average number of hours missed work per day 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 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 10-point scale, where higher score indicated lower work performance.	Month 12

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, 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). pii: e001395. doi: 10.1136/rmdopen-2020-001395.
• 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.
• Bergman M, Tundia N, Yang M, Orvis E, Clewell J, Bensimon A. Economic Benefit from Improvements in Quality of Life with Upadacitinib: Comparisons with Tofacitinib and Methotrexate in Patients with Rheumatoid Arthritis. Adv Ther. 2021 Dec;38(12):5649-5661. doi: 10.1007/s12325-021-01930-4. Epub 2021 Oct 12.
• 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.
• van Vollenhoven RF, Lee EB, Fallon L, Zwillich SH, Wilkinson B, Chapman D, DeMasi R, Keystone E. Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6. Arthritis Care Res (Hoboken). 2019 Jan;71(1):71-79. doi: 10.1002/acr.23585.
• Genovese MC, van Vollenhoven RF, Wilkinson B, Wang L, Zwillich SH, Gruben D, Biswas P, Riese R, Takiya L, Jones TV. Switching from adalimumab to tofacitinib in the treatment of patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Jun 23;18:145. doi: 10.1186/s13075-016-1049-3.
• van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, Garcia Meijide JA, Wagner S, Forejtova S, Zwillich SH, Gruben D, Koncz T, Wallenstein GV, Krishnaswami S, Bradley JD, Wilkinson B; ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012 Aug 9;367(6):508-19. doi: 10.1056/NEJMoa1112072. Erratum In: N Engl J Med. 2013 Jul 18;369(3):293.

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): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: February 27, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (Estimate): March 2, 2009

Study Record Updates

• Last Update Posted (Estimate): January 18, 2013
• Last Update Submitted That Met QC Criteria: January 10, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: clinical trial; JAK inhibitor; oral DMARD
• 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; Anti-Inflammatory Agents; Antirheumatic Agents; Protein Kinase Inhibitors; Adalimumab; Tofacitinib
• Other Study ID Numbers: A3921064