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Randomized Controlled Trial
. 2022 Jun;81(6):798-804.
doi: 10.1136/annrheumdis-2021-221915. Epub 2022 Jan 13.

Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study

Farzin Khosrow-Khavar  1 , Seoyoung C Kim  1   2 , Hemin Lee  1 , Su Been Lee  1 , Rishi J Desai  3
Affiliations
Randomized Controlled Trial

Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study

Farzin Khosrow-Khavar et al. Ann Rheum Dis. 2022 Jun.

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.

Keywords: antirheumatic agents; arthritis; epidemiology; rheumatoid; rheumatoid arthritis.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Forest plot of propensity score fine stratification weighted hazard ratios and corresponding 95% confidence intervals for composite cardiovascular outcomes when comparing tofacitinib with tumor necrosis factor inhibitors in patients with rheumatoid arthritis in RWE cohort (top panel) and RCT-duplicate cohort (bottom panel)
Figure 2.
Figure 2.
Forest plot of propensity score fine stratification weighted hazard ratios and corresponding 95% confidence intervals for composite cardiovascular outcomes for subgroup analyses in RWE study cohort
See this image and copyright information in PMC

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