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Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study
  1. Farzin Khosrow-Khavar1,
  2. Seoyoung C Kim1,2,
  3. Hemin Lee1,
  4. Su Been Lee1,
  5. Rishi J Desai1
  1. 1 Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Massachusetts, USA
  2. 2 Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Rishi J Desai, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, Massachusetts, USA; RDESAI{at}BWH.HARVARD.EDU

Abstract

Objectives Recent results from ‘ORAL Surveillance’ trial have raised concerns regarding the cardiovascular safety of tofacitinib in patients with rheumatoid arthritis (RA). We further examined this safety concern in the real-world setting.

Methods We created two cohorts of patients with RA initiating treatment with tofacitinib or tumour necrosis factor inhibitors (TNFI) using deidentified data from Optum Clinformatics (2012–2020), IBM MarketScan (2012–2018) and Medicare (parts A, B and D, 2012–2017) claims databases: (1) A ‘real-world evidence (RWE) cohort’ consisting of routine care patients and (2) A ‘randomised controlled trial (RCT)-duplicate cohort’ mimicking inclusion and exclusion criteria of the ORAL surveillance trial to calibrate results against the trial findings. Cox proportional hazards models with propensity score fine stratification weighting were used to estimate HR and 95% CIs for composite outcome of myocardial infarction and stroke and accounting for 76 potential confounders. Database-specific effect estimates were pooled using fixed effects models with inverse-variance weighting.

Results In the RWE cohort, 102 263 patients were identified of whom 12 852 (12.6%) initiated tofacitinib. The pooled weighted HR (95% CI) comparing tofacitinib with TNFI was 1.01 (0.83 to 1.23) in RWE cohort and 1.24 (0.90 to 1.69) in RCT-duplicate cohort which aligned closely with ORAL-surveillance results (HR: 1.33, 95% CI 0.91 to 1.94).

Conclusions We did not find evidence for an increased risk of cardiovascular outcomes with tofacitinib in patients with RA treated in the real-world setting; however, tofacitinib was associated with an increased risk of cardiovascular outcomes, although statistically non-significant, in patients with RA with cardiovascular risk factors.

Trial registration number NCT04772248.

  • rheumatoid arthritis
  • antirheumatic agents
  • arthritis
  • rheumatoid
  • epidemiology

Data availability statement

Data may be obtained from a third party and are not publicly available. The databases used in the study can be accessed through a license with MarketScan, Optum, and Medicare. No additional data are available from the authors.

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Data availability statement

Data may be obtained from a third party and are not publicly available. The databases used in the study can be accessed through a license with MarketScan, Optum, and Medicare. No additional data are available from the authors.

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors RJD had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: RJD, SCK and FK-K. Analysis of data: RJD, FK-K and SBL. Interpretation of data and drafting of the manuscript: all authors. RJD acts as guarantor and accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish.

  • Funding This study was funded by internal sources of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital & Harvard Medical School, Boston, MA, USA. SCK is supported by the National Institutes of Health (NIH) grant - K24AR078959. FK-K is supported by a postdoctoral fellowship from Fonds de recherche du Québec-Santé (FRQS). This work was previously presented at American College of Rheumatology Convergence 2021 Meeting (Abstract 1939): FK-K, SCL, HL, SBL and RJD. Risk of Cardiovascular Outcomes in Patients Treated with Tofacitinib: First Results from the Safety of TofAcitinib in Routine Care Patients with Rheumatoid Arthritis (STAR-RA) Study. 2021.

  • Competing interests RJD has received research grants to the Brigham and Women’s Hospital from Bayer, Novartis, and Vertex for unrelated projects. SCK has received research grants to the Brigham and Women’s Hospital from Roche/Genentech, Pfizer, Bristol-Myers Squibb, Roche, and AbbVie for unrelated studies. All other authors have no conflict of interests to disclose.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.