Study to Evaluate Safety and Effects of Tofacitinib and Biologic Disease Modifying Antirheumatic Drugs in People Treated for Rheumatoid Arthritis

An Observational Study Within the CorEvitas Registry to Evaluate Safety and Effectiveness of Tofacitinib and Biologic Disease Modifying Antirheumatic Drugs (bDMARDs) in Japan Among Patients Treated for Moderately to Severely Active Rheumatoid Arthritis

This is a secondary structured database observational study conducted in Rheumatoid Arthritis (RA) patients treated with biologic and nonbiologic DMARDs, including tofacitinib, collected as part of the CorEvitas Japan RA Registry.

The data as of September 2022 will be used for this study. The study will include data from March 2016 to the latest data cut available in 2022 for both effectiveness and safety outcomes.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid

• Study Type: Observational
• Enrollment (Actual): 1972

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Pfizer

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants in an existing registry database

Description

Inclusion Criteria:

• Diagnosed with Rheumatoid Arthritis (RA) according to the 1987 American College of Rheumatology (ACR) or the ACR/European Lead Against Rheumatism (EULAR) 2010 RA Classification Criteria;
• At least 18 years of age or older;
• Was / Must be prescribed or switching to the following eligible medication for the first time ever at the enrollment visit:
• csDMARD: methotrexate (closed in February 2018);
• Anti-TNF bDMARD: adalimumab (originator or biosimilar), certolizumab pegol, etanercept (originator or biosimilar), golimumab, infliximab (originator or biosimilar), or any other anti-TNF biosimilar approved during the study;
• Non-TNF bDMARD: abatacept, tocilizumab, sarilumab (closed in June 2020);
• JAK inhibitor: tofacitinib, baricitinib, peficitinib, filgotinib, upadacitinib.

Exclusion Criteria:

• Data that are prior to March 2016 and after June 2022

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Rheumatoid Arthritis (RA) patients treated with biologic and nonbiologic DMARDs; to include all Japanese patients taking Tofacitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Incidence Rate of Total Cardiovascular Disease (CVD) Events	Incidence rate was defined as participants with total CVD events per (/) 100 person years. Total CVD was defined as hypertension requiring hospitalization, cardiac revascularization procedure (CABG, stent, angioplasty), ventricular arrhythmia, cardiac arrest, myocardial infarction, acute coronary syndrome, unstable angina, congestive heart failure (CHF) requiring hospitalization, stroke, transient ischemic attack, other cardiovascular event (specify), deep vein thrombosis, peripheral arterial thromboembolic event, urgent peripheral arterial revascularization, peripheral ischemia or gangrene (necrosis) and pulmonary embolism. Index visit was defined as the initiation date of the therapy of interest. Mean of incidence rate of total CVD events was calculated and reported.	Retrospective data collection from index visit date up to follow-up or latest data cut on 30 June 2022 (Approximately up to 75 months)
Mean Incidence Rate of Serious Infections Events	Incidence rate was defined as mean number of participants with serious infection events per 100 person years. Total serious infections were defined as infections meeting serious adverse event criteria or which required treatment with intravenous (IV) antibiotics. Serious infection types collected in the registry were pneumonia, sepsis, joint/bursa, cellulitis/skin, sinusitis, diverticulitis, bronchitis, gastroenteritis, meningitis/encephalitis, urinary tract infection, upper respiratory infection, active tuberculosis and other serious infections. Mean of incidence rate of total serious infection events was calculated and reported.	Retrospective data collection from index visit date up to follow-up or latest data cut on 30 June 2022 (Approximately up to 75 months)
Mean Incidence Rate of Total Herpes Zoster Events	Incidence rate was defined as mean number of participants with total Herpes Zoster events per 100 person years. Total herpes zoster included both serious and non-serious herpes zoster events. Mean of incidence rate of total herpes zoster events was calculated and reported.	Retrospective data collection from index visit date up to follow-up or latest data cut on 30 June 2022 (Approximately up to 75 months)
Mean Incidence Rate of Total Malignancy Excluding Non-Melanoma Skin Cancer (NMSC)	Incidence rate (number of participants with event per 100 person year) was defined as the mean number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Total malignancy excluding non-melanoma skin cancer included lymphoma, lung cancer, breast cancer, skin cancer (melanoma), and other cancers. Mean of incidence rate of total malignancy excluding non-melanoma skin cancer was calculated and reported.	Retrospective data collection from index visit date up to follow-up or latest data cut on 30 June 2022 (Approximately up to 75 months)
Mean Change From Baseline in Clinical Disease Activity Index (CDAI) at 6 Months	CDAI was the numerical sum of four outcome parameters: Tender joint count (TJC) or swollen joint count (SJC) both based on a 28-joint assessment, participant's assessment (PtGA) of disease activity and physician's global assessment (PGA) of disease activity both assessed on a 0 to 10 centimeter (cm) visual analogue scale (VAS) (higher scores indicated greater affection due to disease activity). CDAI total score ranged from 0 to 76. Higher scores indicated greater affection due to disease activity. CDAI less than or equal to (<=) 2.8 indicated disease remission, greater than (>) 2.8 to 10 indicated low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicated high disease activity. Mean change from baseline was calculated by subtracting the baseline value from the 6-month value.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Mean Change From Baseline in Japanese Health Assessment Questionnaire (J-HAQ) at 6 Months	HAQ: 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, 0 to 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. Higher scores indicated worse functioning. Mean change from baseline was calculated by subtracting the baseline value from the 6-month value.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Mean Change From Baseline in Participant's Pain at 6 Months	Participants were asked the following question to answer on a numeric rating scale (NRS): "How much pain have you had because of your arthritis in the past week?" The scale ranged from 0-100, where 0=no pain and 100=pain as bad as it could be. Higher scores indicated worsening of condition. Mean change from baseline in participant's pain was calculated and reported.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Mean Change From Baseline in Participant's Fatigue at 6 Months	Visual Analogue Scale (VAS) was a standardized tool for measuring overall health. Participants recorded their fatigue score on a range of 0 to 100, where higher score indicated higher intensity of fatigue. Mean change from baseline in participant's fatigue was calculated and reported.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Mean Change From Baseline in Participant's Global Assessment at 6 Months	Participant's global assessment of disease activity on a 100 millimeter (mm) Visual Analog Scale (VAS) (scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicated worse health condition). Mean change from baseline was calculated by subtracting the baseline value from the 6-month value.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Mean Change From Baseline in Morning Stiffness at 6 Months	CDAI and other continuous measures like morning stiffness were represented as mean change from baseline to 6-months and were calculated by subtracting the baseline value from the 6-month value.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Change in Percentage of Participants Reporting Moderate/Severe/Extreme Difficulty Levels for EQ-5D-5L From Baseline at Month 6	EQ-5D-5L was a participant rated questionnaire to assess health-related quality of life. It assessed level of current health in 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each domain had 5 levels: 1= no problems, 2=slight problems, 3=moderate problems, 4=severe problems, or 5=extreme problems/unable to do task. Total score for each domain was from 1-5, where higher levels/scores indicated more difficulty in each domain. At baseline and 6 months, percentage of participants who recorded "moderate", "severe" or "extreme problems" level in each of the domain were assessed; then change was calculated in percentage of participants from baseline at Month 6 and was reported in this outcome measure.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Percentage of Participants Who Achieved Minimally Clinically Important Difference (MCID) Improvement at 6 Months	MCID improvement assessed based on CDAI. CDAI: numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-10 cm VAS; CDAI total score = 0-76, higher scores=greater affection due to disease activity (DA). CDAI <= 2.8 indicates disease remission, > 2.8 to 10 = low DA, >10 to 22 = moderate DA, and >22 = high DA. MCID improvement defined by difference in CDAI from baseline (at time of tofacitinib initiation) to 6-month visit.	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Percentage of Participants Who Achieved Modified American College of Rheumatology (mACR) 20 Response Score at 6 Months	mACR20 response: >= 20 percent (%) improvement in tender and swollen joint count and 20% improvement in 2 of the following 4 criteria: 1) participant assessment of pain (scored from 0 to 100, higher scores indicated worsening of pain); 2) participant global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 3) physician global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 4) self-assessed disability index of the j-HAQ (scored from 0 to 3, higher scores indicated worsening of function).	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Percentage of Participants Who Achieved mACR 50 Response Score at 6 Months	mACR50 response: >= 50% improvement in tender and swollen joint count and 50% improvement in 2 of the following 4 criteria: 1) participant assessment of pain (scored from 0 to 100, higher scores indicated worsening of pain); 2) participant global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 3) physician global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 4) self-assessed disability index of the j-HAQ (scored from 0 to 3, higher scores indicated worsening of function).	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)
Percentage of Participants Who Achieved mACR 70 Response Score at 6 Months	mACR70 response: >= 70% improvement in tender and swollen joint count and 70% improvement in 2 of the following 4 criteria: 1) participant assessment of pain (scored from 0 to 100, higher scores indicated worsening of pain); 2) participant global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 3) physician global assessment of disease activity (scored from 0 to 100, higher scores indicated worsening of condition); 4) self-assessed disability index of the j-HAQ (scored from 0 to 3, higher scores indicated worsening of function).	Baseline, Month 6 (Retrospective data collection from 01 March-2016 to 30-Jun-2022)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline to 6-months of CDAI	The Clinical Disease Activity Index(CDAI) is the sum of 4 outcome parameters: tender and swollen joint counts (28 joints assessed) and patient's and physician's global assessments of disease activity (on a 0-10-cm visual analog scale). Range of possible scores is 0-76.	Index date, 6-month follow-up visit
Mean change from baseline to 6-months of J-HAQ	J-HAQ is Japanese version of the HAQ-DI. The Health Assessment Questionnaire-Disability Index (HAQ-DI) assesses the degree of difficulty a subject has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question in the questionnaire, the level of difficulty is scored from 0 to 3 with 0 representing "no difficulty," 1 as "some difficulty," 2 as "much difficulty," and 3 as "unable to do". Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status	Index date, 6-month follow-up visit
Mean change from baseline to 6-months of patient pain VAS	Patient pain VAS scale is measured on a visual analog scale ranging from 0 (no pain) to 100 mm (worst pain).	Index date, 6-month follow-up visit
Mean change from baseline to 6-months of patient global assessment VAS	Patient global assessment VAS is measured on a visual analog scale ranging from 0 (no arthritis activity) to 100 mm (extremely active arthritis).	Index date, 6-month follow-up visit
Mean change from baseline to 6-months of patient fatigue VAS	Patient fatigue VAS is measured on a visual analog scale ranging from 0 (no fatigue) to 100 mm (worst fatigue).	Index date, 6-month follow-up visit
Mean change from baseline to 6-months of morning stiffness	Patient morning stiffness assesses the length of time of morning stiffness (in hours/minutes).	Index date, 6-month follow-up visit
Mean change from baseline to 6-months of EA-5D-5L	The EQ 5D 5L is a validated health outcomes instrument that generates a simple descriptive profile on 5 domains of health. The domains are rated on 5 levels, and the instrument is composed of both a short, cognitively simple questionnaire and a VAS scale.	Index date, 6-month follow-up visit
Achievement of minimally clinically important difference (MCID) at 6-month follow-up	Achievement of minimally clinically important difference (MCID) [4] at 6-month follow-up, based on the CDAI value at initiation. Specifically, MCID > 1 if CDAI at baseline is ≤ 10, MCID > 6 if CDAI at baseline ranges between (10, 22], MCID > 12 if CDAI at baseline > 22.	6-month follow-up visit
Modified ACR20/50/70	Modified ACR20/50/70 (mACR20/50/70), defined as 20/50/70% improvement in tender and swollen joint count, and 20/50/70% improvement in 2 of the following four domains at the 6-month follow-up visit: patient pain assessment, patient global assessment, physician global assessment, patient self-addressed disability, measured by the J-HAQ score.	6-month follow-up visit

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2022
• Primary Completion (Actual): October 10, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: October 5, 2022
• First Submitted That Met QC Criteria: October 5, 2022
• First Posted (Actual): October 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 8, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: A3921429

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.