Cardiovascular Safety of Tofacitinib in Real-World Clinical Practice – Results of the STAR-RA Study
Recent results from the ORAL Surveillance clinical trial have raised concerns about the cardiovascular adverse effects of tofacitinib in patients with rheumatoid arthritis. A comprehensive analysis of real-world clinical practice data, involving nearly 13,000 patients, focused on the cardiovascular safety of tofacitinib for this indication.
Cardiovascular Risks of RA and Tofacitinib
Rheumatoid arthritis (RA) is characterized by systemic inflammation, which leads to joint damage as well as extra-articular manifestations, including cardiovascular disease. Tofacitinib is a Janus kinase inhibitor (JAKi) that achieves efficacy comparable to biological treatment in patients with RA.
Recently published results from the post-marketing safety study ORAL Surveillance suggested a potential increased risk of major adverse cardiovascular events (MACE) with tofacitinib treatment compared to tumor necrosis factor inhibitors (TNFi) among patients aged ≥ 50 years and with ≥ 1 additional cardiovascular risk factor.
The aim of the presented analysis was to further investigate the cardiovascular risk of tofacitinib treatment in real-world clinical practice conditions.
Analysis Methodology
The study authors used anonymized data from the databases of several health insurance companies in the USA from 2012−2020, creating two cohorts of RA patients who started treatment with tofacitinib or TNF inhibitors. The first cohort, called RWE (real-world evidence), consisted of patients from routine clinical practice. The second cohort, called RCT-duplicate (randomized controlled trial duplicate), mimicked the inclusion and exclusion criteria of the ORAL Surveillance clinical trial to calibrate the analysis results against the results of this study.
To estimate the hazard ratios (HR) and 95% confidence intervals (CI), the Cox proportional hazards model with fine stratification propensity score weighting was used. The model estimated the composite endpoint – the risk of myocardial infarction and/or stroke, considering 76 potential confounding variables. Database-specific effect estimates were pooled using fixed-effects models with inverse variance weighting.
Results
The RWE cohort included 102,263 patients, of whom 12,852 (12.6%) started treatment with tofacitinib. The pooled weighted hazard ratio for myocardial infarction and/or stroke in this cohort for tofacitinib versus TNFi was 1.01 (95% CI 0.83−1.23). Increased cardiovascular risk was observed in patients with a history of cardiovascular disease (HR 1.27; 95% CI 0.95−1.70) but not in patients without this history (HR 0.81; 95% CI 0.61−1.07).
In the RCT-duplicate cohort, the hazard ratio for the primary endpoint was 1.24 (95% CI 0.90−1.69), consistent with the results of the ORAL Surveillance study (HR 1.33; 95% CI 0.91−1.94).
Conclusion
The analysis did not demonstrate an increase in cardiovascular risk for patients in real-world clinical practice. The use of tofacitinib was associated with a statistically non-significant increase in cardiovascular risk in RA patients with pre-existing cardiovascular risk factors or coronary artery disease before starting treatment.
(este)
Source: Khosrow-Khavar F., Kim S. C., Lee H. et al. 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; 81 (6): 798−804, doi: 10.1136/annrheumdis-2021-221915.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.