LONDON -- Baricitinib (Olumiant) failed to show noninferiority to tumor necrosis factor (TNF) inhibitors for venous thromboembolism (VTE) risk in FDA-required postmarketing studies, a researcher reported here.
In two large randomized trials with up to 6 years of follow-up in patients -- ordered by the FDA as a condition of baricitinib's approval in 2018 for rheumatoid arthritis (RA) -- those treated with the Janus kinase (JAK) inhibitor suffered VTE events at a rate of 2.5%, compared with 1.7% among those assigned to adalimumab (Humira) or etanercept (Enbrel), according to Torsten Witte, MD, of Hannover Medical School in Germany.
That yielded a hazard ratio of 1.61 (95% 0.969-2.660) for time to first VTE event. While not a statistically significant difference, the FDA-approved protocol set a maximum upper bound of 1.8 for the confidence interval to declare noninferiority, which was far exceeded, Witte told attendees at a packed late-breaking abstract session at the European Alliance of Associations for Rheumatology's (EULAR) annual meeting.
Baricitinib already carries a boxed warning about VTE risk (as well as risks for major cardiovascular events and certain infections and malignancies). But the VTE, heart, and cancer risks were based on a presumed class effect stemming from the famous ORAL Surveillance study with tofacitinib (Xeljanz), the first JAK inhibitor to win FDA approval. The manufacturer of that drug, Pfizer, was required to conduct ORAL Surveillance after its clinical program suggested higher risks relative to TNF inhibitors such as adalimumab.
