FDA Requires New Warning Labels for Most JAK Inhibitors

The U.S. Food and Drug Administration (FDA) announced September 1 that it will now require updated warnings of heightened risks for heart attack, stroke, blood clots, and cancer on Janus kinase (JAK) inhibitors used for inflammatory conditions, including ulcerative colitis, psoriatic arthritis, and rheumatoid arthritis.

In its Drug Safety Communication, FDA noted that baricitinib and upadacitinib “have not been studied in trials similar to the large safety clinical trial with Xeljanz [tofacitinib], so the risks have not been adequately evaluated. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.”

The agency is also limiting approved use of these JAK inhibitors to patients who have not responded to or cannot tolerate anti-TNFs.

The FDA action comes after its review of a randomized safety clinical trial concluded that tofacitinib, which already carried a boxed warning for these risks at the 10 mg per day dose, also showed increased risks at the 5 mg per day dose when compared with anti-tumor necrosis factor (TNF) therapeutics.

The trial also showed a higher rate of lymphomas and a increased rate of lung cancers in current or past smokers treated with tofacitinib compared to those treated with anti-TNFs.

The JAK inhibitors ruxolitinib and fedratinib are not indicated for inflammatory conditions and therefore are unaffected by this requirement for labeling changes.

--Rebecca Mashaw

Reference:

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. [Drug Safety Communication]. Silver Spring, MD. US Food and Drug Administration; September 1, 2021. Linked Here. Accessed September 2, 2021.