FDA Approves JAK Inhibitor to Treat Ulcerative Colitis, Providing an Alternative to Anti-TNF Agents

This week, the FDA approved an expanded indication of the Janus kinase (JAK) inhibitor tofacitinib (Xeljanz) to include adults with moderate to severe ulcerative colitis (UC). Tofacitinib is the first oral medicine approved for long-term use in UC, and provides an alternative to anti—tumor necrosis factor (anti-TNF) drugs that must be injected or infused.

The “approval provides an alternative therapy for a debilitating disease with limited treatment options,” said Julie Beitz, MD, director of the Office of Drug Evaluation in FDA’s Center for Drug Evaluation and Research, in a statement.

The approval was based on data collected from 3 controlled clinical trials. In 2 different 8-week placebo-controlled trials, 10 mg of tofacitinib, administered twice daily, resulted in remission in 17% to 18% of patients by week 8. Of these patients, 35% and 47% achieved sustained, corticosteroid-free remission when treated with 5 mg or 10 mg, respectively.

In the final placebo-controlled clinical trial, tofacitinib was administered at a 5-mg or 10-mg dose twice daily. Among patients in the study who achieved a clinical response by week 8, the drug induced remission by week 52 in 34% and 41% of patients, respectively.

The most commonly reported adverse events (AEs) were diarrhea, elevated cholesterol levels, headache, rash, upper respiratory tract infection, herpes zoster, increased blood creatine phosphokinase, and the common cold. Less common serious AEs seen in the studies included malignancy and serious infections, such as opportunistic infections.

However JAK inhibitors as a class have recently come under increased examination after the FDA’s Adverse Events Reporting System revealed 18 primary cases of pulmonary embolism in patients taking tofacitinib.

This heightened incidence of thromboembolic adverse events has also been seen in ruxolitinib (Jakafi), drawing concerns of whether the safety issue may be class-wide for JAK inhibitors. Then, in April 2018, the FDA’s Arthritis Advisory Committee voted in favor of recommending approval of a low dose of the JAK inhibitor baricitinib to treat rheumatoid arthritis, and against recommending approval of a higher dose, because of concerns about safety that included the risk of thrombosis. On June 1, the FDA approved baricitinib as Olumiant at the lower, 2-mg dose, and required a black-box safety warning for thrombosis as well as serious infections and malignancy.