RAPS recognizes that the current situation in Ukraine impacts our members and customers on many levels. If you are directly impacted by the current situation in the region and are challenged to meet your deadlines or obligations to RAPS, please reach out to raps@raps.org so that we can defer those challenges. Your health and safety are paramount to us.

Regulatory Focus™ > News Articles > 2021 > 9 > JAK inhibitors' CV, cancer risks merit expanded boxed warning

JAK inhibitors' CV, cancer risks merit expanded boxed warning

Posted 02 September 2021 | By Kari Oakes 

JAK inhibitors' CV, cancer risks merit expanded boxed warning

The boxed warnings for several members of a class of drugs used to treat a number of inflammatory conditions must be revised to reflect the increased risk of cancer, serious cardiovascular problems and death seen in people taking the drugs, according to a new drug safety communication from the US Food and Drug Administration (FDA).
The revisions come after safety data from a randomized clinical trial of Pfizer’s Xeljanz (tofacitinib) and is extended release formulation, Xeljanz XR, showed an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” in patients with rheumatoid taking the medicines, announced FDA in a MedWatch notification released Thursday. The increased risk was seen in those taking Xeljanz, but not in a comparator group taking tumor necrosis factor inhibitors.
Similar boxed warnings are now required for two other Janus kinase (JAK) inhibitors. Large safety trials have not yet been conducted that could detect such risks for Eli Lilly’s Olumiant (baricitnib) and AbbVie’s Rinvoq (upadacitinib), but “since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial,” wrote FDA.
The concerning increases in serious complications and death with Xeljanz were seen in the required post-marketing ORAL safety study that enrolled nearly 1,500 patients and randomized them to two different doses of tofacitinib, an oral medication, or to a TNFi taken by subcutaneous injection.
FDA is not requiring that two other JAK inhibitors, Incyte’s Jakafi (ruxolitinib) and Celgene’s Inrebic (fedratinib), carry the warnings, since they are not used to treat inflammatory conditions.


© 2022 Regulatory Affairs Professionals Society.