Safety of TofAcitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA)- Cardiovascular Endpoints

Study Overview
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Brief Summary
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There are two main aims of this study. First aim is to compare the risk of cardiovascular events (including myocardial infarction or stroke), between patients treated with tofacitinib and patients treated with TNF inhibitors (TNFi) for rheumatoid arthritis (RA) among, 1) real world evidence (RWE) cohorts including routine care patient population from the US and, 2) Randomized controlled trial (RCT) DUPLICATE cohorts including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis (ORAL Surveillance, NCT02092467) clinical trial. Second aim is to examine the risk of myocardial infarction, stroke, heart failure hospitalization, coronary revascularization, and all-cause mortality as separate endpoints when comparing tofacitinib with TNFi in patients with RA among, 1) real world evidence (RWE) cohort including routine care patient population from the US and, 2) Randomized controlled trial (RCT) DUPLICATE cohort including routine care patient population who meet inclusion and exclusion criteria of the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis (ORAL Surveillance, NCT02092467) clinical trial.

Official Title
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Safety of TofAcitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA)- Cardiovascular Endpoints

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tofacitinib
* Drug: TNF Inhibitor


Participation Criteria
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Eligibility Criteria
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Criteria: Please see https://www.bwhprime.org/resources.html for full code and algorithm definitions. Eligible cohort entry dates: For US MarketScan, 2012-2018 For Optum, 2012-2020 For Medicare Claims Database (Parts A, B and D), 2012-2017 Cohort entry date: First TNFi or tofacitinib dispensation/administration date Inclusion and Exclusion Criteria Common to RWE and RCT-duplicate Cohorts: Inclusion Criteria Patients treated with tofacitinib or TNF inhibitors in IBM MarketScan, Optum, and Medicare fee-for-service A minimum of 365 days of continuous enrollment in health plan prior to (and including) the cohort entry date Two diagnosis codes for RA in any setting in 365 days baseline period (diagnosis codes between 7 and 365 days apart) Exclusion Criteria Index drug in 365 days prior to cohort entry date (prevalent users) Missing data on age or gender Admission to nursing facility or hospice on or prior to cohort entry date (ever look-back) TNFi users with history of any Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib, or baricitinib) (ever look-back period) TNFi users initiating with more than one TNFi on same date Tofacitinib users with a prescription of baricitinib, upadacitinib (ever look-back period) Tofacitinib users initiating treatment on multiple JAK inhibitors on same day (tofacitinib and baricitinib, tofacitinib and upadacitinib) Exclusion criteria specific to RWE cohorts: Patients less than 18 years of age (MarketScan and Optum) and 65 years of age (Medicare) at cohort entry Inclusion criteria specific to RCT-duplicate cohorts: Patients with at least one methotrexate dispensation (six months look-back period) Patients with at least one cardiovascular risk factor (including smoking, hypertension, dyslipidemia, diabetes mellitus, ischemic heart disease, family history of ischemic heart disease) (one-year look-back period) Exclusion criteria specific to RCT-duplicate cohorts: Patients less than 50 years of age (MarketScan and Optum) and 65 years Patients recently hospitalized with infections (30-day look-back period) Pregnant patients (one year look-back period)

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 |
| --- | --- |
| Patients treated with Tofacitinib<br>Real-World Evidence (RWE) and RCT-Duplicate | Drug: Tofacitinib<br>* First eligible prescription for treating rheumatoid arthritis (RA)<br>|
| Patients treated with TNF inhibitors<br>Real-World Evidence (RWE) and RCT-Duplicate | Drug: TNF Inhibitor<br>* First eligible prescription for treating rheumatoid arthritis (RA)<br>* Other names: golimumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first composite cardiovascular endpoint consisting of myocardial infarction or stroke | Myocardial infarction OR Stroke | Through study time period (2012-2020) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to myocardial infarction |  | Through study time period (2012-2020) | 
| Time to stroke |  | Through study time period (2012-2020) | 
| Time to heart failure hospitalization |  | Through study time period (2012-2020) | 
| Time to coronary revascularization |  | Through study time period (2012-2020) | 
| Time to all-cause mortality |  | Through study time period (2012-2020) |