The Food and Drug Administration (FDA) is requiring new and updated warnings for Janus kinase (JAK) inhibitors Xeljanz/Xeljanz XR (tofacitinib; Pfizer), Olumiant (baricitinib; Eli Lilly and Co.), and Rinvoq (upadacitinib; AbbVie Inc).

The FDA completed a review of a large, randomized safety clinical trial comparing Xeljanz with tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis. The agency concluded that there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR. The trial’s final results also showed an increased risk of blood clots and death with the lower dose of Xeljanz. A prior drug safety communication based upon earlier results from this trial reported an increased risk of blood clots and death only seen at the higher dose.

Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action with Xeljanz, the FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.

Two other JAK inhibitors, Jakafi (ruxolitinib) and Inrebic (fedratinib), are not indicated for the treatment of arthritis and other inflammatory conditions and so are not a part of the updates being required to the prescribing information for Xeljanz, Xeljanz XR, Olumiant, and Rinvoq. Jakafi and Inrebic are used to treat blood disorders and require different updates to their prescribing information. If the FDA becomes aware of any additional safety information or data that warrants updates to the prescribing information for these medicines, the agency may take further action and will alert the public.

Food and Drug Administration (FDA). FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. September 1, 2021. Available at: click here. Accessed September 1, 2021.