Clinical trial NCT04772248: Safety of TofAcitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA)- Cardiovascular Endpoints
Official title: Safety of TofAcitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA)- Cardiovascular Endpoints
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rheumatoid Arthritis
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-02-26
Enrollment: 105711
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: There will be two independent study populations:

1. Real-World Evidence (RWE) cohorts: This study population will reflect the patients diagnosed with RA who are routinely treated and managed in setting of clinical practice.
2. RCT-duplicate cohorts: This study population will emulate "the Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis" clinical trial ("ORAL Surveillance", NCT02092467). The inclusion and exclusion criteria of this RCT will be applied to this study population.

Brief summary: 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.


Eligibility criteria: 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:

1. 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)
2. 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)

Primary outcomes:
measure: Time to first composite cardiovascular endpoint consisting of myocardial infarction or stroke
timeFrame: Through study time period (2012-2020)
Secondary outcomes:
measure: Time to myocardial infarction
timeFrame: Through study time period (2012-2020)
measure: Time to stroke
timeFrame: Through study time period (2012-2020)
measure: Time to heart failure hospitalization
timeFrame: Through study time period (2012-2020)
measure: Time to coronary revascularization
timeFrame: Through study time period (2012-2020)
measure: Time to all-cause mortality
timeFrame: Through study time period (2012-2020)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham And Women's Hospital
state: Massachusetts
Study officials:
affiliation: Assistant Professor of Medicine
name: Rishi Desai, MS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khosrow-Khavar F, Kim SC, Lee H, Lee SB, Desai RJ. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 Jun;81(6):798-804. doi: 10.1136/annrheumdis-2021-221915. Epub 2022 Jan 13.