Study of CP-690,550 Versus Placebo In Rheumatoid Arthritis Patients On Background Methotrexate With Inadequate Response To Tumor Necrosis Factor (TNF) Inhibitors

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 Methotrexate With Inadequate Response To TNF Inhibitors

This study will test if CP-690,550 is safe and effective in rheumatoid arthritis patients taking methotrexate who have an inadequate response to tumor necrosis factor inhibitor treatment.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 399
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Pfizer Investigational Site
  • South Australia
    • Daw Park, South Australia, Australia, 5041
      • Pfizer Investigational Site
  • Victoria
    • Heidelberg, Victoria, Australia, 3081
      • Pfizer Investigational Site
• Austria
  • Wien, Austria, A-1100
    • Pfizer Investigational Site
  • Wien, Austria, 1100
    • Pfizer Investigational Site
  • Wien, Austria, 1090
    • Pfizer Investigational Site
  • Wien, Austria
    • Pfizer Investigational Site
• Belgium
  • Genk, Belgium, 3600
    • Pfizer Investigational Site
  • Hasselt, Belgium, 3500
    • Pfizer Investigational Site
  • Kortrijk, Belgium
    • Pfizer Investigational Site
  • Liège, Belgium, 4020
    • Pfizer Investigational Site
• Brazil
  • GO
    • Goiania, GO, Brazil, 74110-120
      • Pfizer Investigational Site
  • PR
    • Curitiba, PR, Brazil, 80060-240
      • Pfizer Investigational Site
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Pfizer Investigational Site
  • SP
    • Sao Paulo, SP, Brazil, 04266-010
      • Pfizer Investigational Site
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Pfizer Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Pfizer Investigational Site
    • Hamilton, Ontario, Canada, L8N 2B6
      • Pfizer Investigational Site
    • Ottawa, Ontario, Canada, K1H 1A2
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Pfizer Investigational Site
    • Pointe Claire, Quebec, Canada, H9R 3J1
      • Pfizer Investigational Site
• France
  • Amiens, France, 80054
    • Pfizer Investigational Site
  • Lyon, France
    • Pfizer Investigational Site
  • Orleans, France, 45000
    • Pfizer Investigational Site
  • Orleans Cedex 1, France, 45032
    • Pfizer Investigational Site
  • Paris, France, 75014
    • Pfizer Investigational Site
  • Paris, France
    • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Pfizer Investigational Site
  • Berlin, Germany, 14163
    • Pfizer Investigational Site
  • Erlangen, Germany, 91054
    • Pfizer Investigational Site
  • Frankfurt am Main, Germany, 60590
    • Pfizer Investigational Site
  • Halle, Germany, 06108
    • Pfizer Investigational Site
  • Hamburg, Germany, 22081
    • Pfizer Investigational Site
  • Koeln, Germany, 50937
    • Pfizer Investigational Site
  • Leipzig, Germany, 04103
    • Pfizer Investigational Site
  • Rheine, Germany, 48431
    • Pfizer Investigational Site
  • Wuerzburg, Germany, 97080
    • Pfizer Investigational Site
• Ireland
  • Dublin, Ireland, 4
    • Pfizer Investigational Site
  • Co. Limerick
    • Croom, Co. Limerick, Ireland
      • Pfizer Investigational Site
• Italy
  • Firenze, Italy, 50139
    • Pfizer Investigational Site
  • Jesi, Italy
    • Pfizer Investigational Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Pfizer Investigational Site
  • Daegu, Korea, Republic of, 705-718
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 135-720
    • Pfizer Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 00910
    • Pfizer Investigational Site
• Spain
  • Madrid, Spain, 28007
    • Pfizer Investigational Site
  • Valencia, Spain, 46017
    • Pfizer Investigational Site
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15705
      • Pfizer Investigational Site
  • Badajoz
    • Merida, Badajoz, Spain, 06800
      • Pfizer Investigational Site
  • Bizkaia
    • Bilbao, Bizkaia, Spain, 48013
      • Pfizer Investigational Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Pfizer Investigational Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Pfizer Investigational Site
• Taiwan
  • Changhua, Taiwan, 500
    • Pfizer Investigational Site
  • Kaohsiung, Taiwan, 813
    • Pfizer Investigational Site
  • Kaohsiung County
    • Niao Sung Hsiang, Kaohsiung County, Taiwan, 833
      • Pfizer Investigational Site
  • Taoyuan County
    • Kweishan, Taoyuan County, Taiwan, 333
      • Pfizer Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Pfizer Investigational Site
  • California
    • Los Angeles, California, United States, 90095
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90033
      • Pfizer Investigational Site
    • San Diego, California, United States, 92108
      • Pfizer Investigational Site
  • Connecticut
    • Farmington, Connecticut, United States, 06030-5353
      • Pfizer Investigational Site
    • Trumbull, Connecticut, United States, 06611
      • Pfizer Investigational Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33614
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Pfizer Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83702
      • Pfizer Investigational Site
    • Idaho Falls, Idaho, United States, 83404
      • Pfizer Investigational Site
  • Illinois
    • Springfield, Illinois, United States, 62704
      • Pfizer Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46227
      • Pfizer Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Pfizer Investigational Site
  • Maine
    • Portland, Maine, United States, 04102
      • Pfizer Investigational Site
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Pfizer Investigational Site
  • Massachusetts
    • Worcester, Massachusetts, United States, 01610
      • Pfizer Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Pfizer Investigational Site
    • Tupelo, Mississippi, United States, 38801
      • Pfizer Investigational Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Pfizer Investigational Site
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Pfizer Investigational Site
  • North Carolina
    • Rocky Mount, North Carolina, United States, 27804
      • Pfizer Investigational Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015-1153
      • Pfizer Investigational Site
    • Willow Grove, Pennsylvania, United States, 19090
      • Pfizer Investigational Site
    • Wyomissing, Pennsylvania, United States, 19610
      • Pfizer Investigational Site
  • Tennessee
    • Hixson, Tennessee, United States, 37343
      • Pfizer Investigational Site
    • Knoxville, Tennessee, United States, 37909
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37203
      • Pfizer Investigational Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75246
      • Pfizer Investigational Site
    • Fort Worth, Texas, United States, 76107
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77034
      • Pfizer Investigational Site
    • Lubbock, Texas, United States, 79424
      • Pfizer Investigational Site
  • Washington
    • Vancouver, Washington, United States, 98684
      • Pfizer Investigational Site
    • Vancouver, Washington, United States, 98686
      • Pfizer Investigational Site
    • Vancouver, Washington, United States, 98664
      • 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:

• Adults with moderate to severe rheumatoid arthritis on a stable dose of methotrexate who have inadequate response to Tumor Necrosis Factor (TNF) inhibitors.

Exclusion Criteria:

• Pregnancy, severe acute or chronic medical conditions, including serious infections or clinically significant laboratory abnormalities.

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: Sequence 1	Drug: CP-690,550; Oral tablets administered at 5 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 5 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase
Experimental: Sequence 2	Drug: CP-690,550; Oral tablets administered at 5 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 5 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase
Placebo Comparator: Sequence 3	Drug: CP-690,550; Oral tablets administered at 5 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 5 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase; Drug: Placebo; Oral placebo tablets administered BID daily during the first 3 months of the double-blind, study period.; Other Names: double-blind, placebo-controlled phase; Drug: Placebo; Oral placebo tablets administered BID daily during the first 3 months of the double-blind, placebo-controlled period.; Other Names: double-blind, placebo-controlled phase
Placebo Comparator: Sequence 4	Drug: CP-690,550; Oral tablets administered at 5 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily for 6 months during the double-blind, placebo-controlled period.; Drug: CP-690,550; Oral tablets administered at 5 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase; Drug: CP-690,550; Oral tablets administered at 10 mg BID daily during the second 3 months of the double-blind, study period.; Other Names: double-blind, extension phase; Drug: Placebo; Oral placebo tablets administered BID daily during the first 3 months of the double-blind, study period.; Other Names: double-blind, placebo-controlled phase; Drug: Placebo; Oral placebo tablets administered BID daily during the first 3 months of the double-blind, placebo-controlled period.; Other Names: double-blind, placebo-controlled phase

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 3	ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joints count (TJC); >= 20% improvement in swollen joints 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 3 analysis.	Month 3
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 With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3	DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR)(millimeter/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 3 analysis.	Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 2 and Month 1	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.	Week 2, Month 1
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 4.5 and 6	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 4.5, 6
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 2, Month 1 and 3	ACR50 response: >= 50% improvement in TJC or SJC 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.	Week 2, Month 1, 3
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 4.5 and 6	ACR50 response: >= 50% improvement in TJC or SJC 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 4.5 and 6
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 2, Month 1 and 3	ACR70 response: >=70% improvement in TJC or SJC 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.	Week 2, Month 1, 3
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 4.5 and 6	ACR70 response: >=70% improvement in TJC or SJC 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 4.5, 6
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Baseline, Week 2, Month 1 and 3	DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.	Baseline, Week 2, Month 1, 3
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Month 4.5 and 6	DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.	Month 4.5, 6
Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Baseline and Month 3	DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.	Baseline, Month 3
Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Month 6	DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.	Month 6
Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, Month 1 and 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.	Week 2, Month 1, 3
Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 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; 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 4.5, 6
Patient Assessment of Arthritis Pain at Baseline, Week 2, Month 1 and 3	Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.	Baseline, Week 2, Month 1, 3
Patient Assessment of Arthritis Pain at Month 4.5 and 6	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 4.5, 6
Patient Global Assessment (PtGA) of Arthritis Pain at Baseline, Week 2, Month 1 and 3	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, Week 2, Month 1, 3
Patient Global Assessment (PtGA) of Arthritis Pain at Month 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 mm = very well and 100 mm = very poorly.	Month 4.5, 6
Physician Global Assessment of Arthritis at Baseline, Week 2, Month 1 and 3	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, 3
Physician Global Assessment of Arthritis at Month 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.	Month 4.5, 6
36-Item Short-Form Health Survey (SF-36) at Baseline, Week 2, Month 1 and 3	SF-36 is a standardized survey evaluating 8 domains (of 2 components; physical and mental) of functional health and well being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health, vitality, 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, Week 2, Month 1, 3
36-Item Short-Form Health Survey (SF-36) at Month 6	SF-36 is a standardized survey evaluating 8 domains (of 2 components; physical and mental) of functional health and well being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health, vitality, 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).	Month 6
Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Week 2, Month 1 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/no), and 9 item index measures of sleep disturbance provide composite scores:sleep problem summary,overall sleep problem.Except adequacy,optimal sleep and quantity,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, Week 2, Month 1, 3
Medical Outcomes Study Sleep Scale (MOS-SS) at Month 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/no), and 9 item index measures of sleep disturbance provide composite scores:sleep problem summary,overall sleep problem.Except adequacy,optimal sleep and quantity,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 6
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Week 2, Month 1, and 3	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 optimal by choosing yes or no. Number of participants with optimal sleep is reported.	Baseline, Week 2, Month 1, 3
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Month 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 optimal by choosing yes or no. Number of participants with optimal sleep is reported.	Month 6
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Baseline and Month 3	FACIT-Fatigue Scale (FS):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-FS 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 3
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Month 6	FACIT-FS: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-FS 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 6
Euro Quality of Life - 5 Dimensions (EQ-5D)- Health State Profile Utility Score at Baseline, Month 1 and 3	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
Euro Quality of Life - 5 Dimensions (EQ-5D) - Health State Profile Utility Score at Month 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.	Month 6
Work Productivity and Healthcare Resource Utilization (HCRU) at Baseline, Month 3	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
Work Productivity and Healthcare Resource Utilization (HCRU) at Month 6	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 6
Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Baseline and Month 3	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
Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Month 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.	Month 6
Number of Days as Assessed Using RA-HCRU at Baseline and Month 3	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 were reported.	Baseline, Month 3
Number of Days as Assessed Using RA-HCRU at Month 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 were reported.	Month 6
Number of Hours Per Day as Assessed RA-HCRU at Baseline and Month 3	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
Number of Hours Per Day as Assessed RA-HCRU at Month 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.	Month 6
Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Baseline and Month 3	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
Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Month 6	Work performance of participants on number of days bothered was based on 10-point scale, where higher score indicated lower work performance.	Month 6
Work Limitations Questionnaire (WLQ) Score at Baseline and Month 3	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 (TMS)(5-items); Physical Demands scale (PDS) (6-item); Mental-Interpersonal Demands Scale (MIDS) (9-items); Output Demands Scale (ODS) (5-items). 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 3
Work Limitations Questionnaire (WLQ) Score at Month 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 (TMS)(5-items); Physical Demands scale (PDS) (6-item); Mental-Interpersonal Demands Scale (MIDS) (9-items); Output Demands Scale (ODS) (5-items). 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 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) Less Than 2.6 and Less Than or Equal to 3.2 at Week 2, Month 1 and 3	DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0-9.4, higher score=more disease activity. DAS28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.	Week 2, Month 1, 3
Number of Participants With Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 4.5 and 6	DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0-9.4, higher score=more disease activity. DAS28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.	Month 4.5, 6
Number of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 3	DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.	Month 3
Number of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 6	DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment). Total score range: 0-9.4, higher score=more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.	Month 6

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.
• Vieira MC, Zwillich SH, Jansen JP, Smiechowski B, Spurden D, Wallenstein GV. Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis. Clin Ther. 2016 Dec;38(12):2628-2641.e5. doi: 10.1016/j.clinthera.2016.11.004. Epub 2016 Nov 24.
• 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.
• 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.
• Mariette X, Chen C, Biswas P, Kwok K, Boy MG. Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program. Arthritis Care Res (Hoboken). 2018 May;70(5):685-694. doi: 10.1002/acr.23421. Epub 2018 Apr 2.
• Strand V, Burmester GR, Zerbini CA, Mebus CA, Zwillich SH, Gruben D, Wallenstein GV. Tofacitinib with methotrexate in third-line treatment of patients with active rheumatoid arthritis: patient-reported outcomes from a phase III trial. Arthritis Care Res (Hoboken). 2015 Apr;67(4):475-83. doi: 10.1002/acr.22453.
• Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, Gruben D, Wallenstein G, Krishnaswami S, Zwillich SH, Koncz T, Soma K, Bradley J, Mebus C; ORAL Step investigators. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013 Feb 9;381(9865):451-60. doi: 10.1016/S0140-6736(12)61424-X. Epub 2013 Jan 5.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: August 14, 2009
• First Submitted That Met QC Criteria: August 14, 2009
• First Posted (Estimate): August 17, 2009

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: November 29, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: randomized double-blind placebo-controlled investigational drug oral therapy safety and efficacy
• 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: A3921032