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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Arthritis, Rheumatoid

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Rheumatoid Arthritis (RA) patients treated with biologic and nonbiologic DMARDs<br>to include all Japanese patients taking Tofacitinib | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rates of selected safety events of interest | Safety events of interest ie. total CVD, serious infections, total Herpes Zoster, and total malignancy excluding NMSC (non-melanoma skin cancer) in the Tofacitinib, non-TNF, anti-TNFi, and MTX cohorts by estimating marginal means of incidence rates of selected safety events of interest. | Index date, 90 days after the end of therapy or end of data collection | 

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 |