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Deepak Bhatt, MD, MPH, discusses a posthoc analysis of the ORAL Surveillance trial examining drivers of increased cardiovascular risk observed in the phase 3b/4 trial in patients with rheumatoid arthritis.
Further analysis of data from the ORAL Surveillance trial is providing clinicians with new insight into the increased risk of major adverse cardiovascular events observed with use of tofacitinib in patients with rheumatoid arthritis.
Presented at the American College of Rheumatology (ACR) Convergence 2022, results of the posthoc analysis demonstrate the risk of a composite of all ischemic cardiovascular and heart failure events did not appear to be different between use of tofacitinib and TNF inhibitors and the increased cardiovascular risk observed in the trial was driven by an increase in venous thromboembolism events.
A phase 3b/4 randomized, post-authorization safety study launched with the intent of examining whether use of tofacitinib might increase risk of major adverse cardiovascular events or cancer compared against use of TNF inhibitors, the ORAL Surveillance trial enrolled and randomized 4362 adults with rheumatoid arthritis in a 1:1:1 ratio to receive tofacitinib at a dose of 5 mg twice daily, tofacitinib at a dose of 10 mg twice daily, or a TNF inhibitor.
In the trial, which included a median follow-up of 4.0 years, results indicated incidences of MACE and cancer were higher with the combined tofacitinib doses (3.4% [98 patients] vs 4.2% [122 patients], respectively) than with a TNF inhibitor (2.5% [37 patients] and 2.9% [42 patients]). In the posthoc analysis, investigators sought to determine specific drivers of the increased risk observed in the trial. To do so, the analyses examined risk of cardiovascular events by expanding on 3-point MACE and evaluating risk of all adjudicated cardiovascular events in the trial in a sequential manner.
Results of the investigators’ analysis demonstrated expansion of the 3-point MACE endpoints up to and including MACE-8 did not significantly alter hazard ratios compared to those observed for the 3-point MACE endpoint. However, expanding to MACE-8 plus VTE indicated risk was greater with tofacitinib 10 mg twice daily compared to TNF inhibitor use, which was not observed with use of tofacitinib 5 mg twice daily (HR, 1.12 [95% CI, 0.82-1.52]). Further analysis indicated risk of myocardial infarction appear to be greater with tofacitinib, but risk of other individual adjudicated cardiovascular events was generally similar. Overall, investigators noted a trend for increased risk observed with tofacitinib use compared to use of TNF inhibitors among those with a history of ASCVD.
For more on this study and how it might influence treatment choices, our editorial team reached out to Deepak Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and that conversation is the subject of the following video.
This study, “Risk of Extended Major Adverse Cardiovascular Event Endpoints with Tofacitinib vs TNF Inhibitors in Patients with Rheumatoid Arthritis: A Post Hoc Analysis of a Phase 3b/4 Randomized Safety Study,” was presented at ACR Convergence 2022.