When FDA approved the Pfizer drug product tofacitinib (Xeljanz, Xeljanz XR), which treats arthritis and ulcerative colitis by decreasing the activity of the immune system, they required that Pfizer conduct post-approval safety trials to evaluate the risk of serious heart-related events, cancer and infections.

Tofacitinib is offered in two strengths which were both studied in the trials; the originally approved dosing was 5 mg twice a day for Rheumatoid Arthritis (RA) or Psoriatic arthritis (PsA) and 10 mg twice a day for ulcerative colitis (initial treatment and for long-term use in limited situations).  As Lachman shared in this blog on July 26, 2019 (here), the post-marketing study revealed a higher risk of blood clots and death for patients taking the 10 mg dose when compared to patients taking the 5 mg twice daily approach or alternate treatments using tumor necrosis factor (TNF) inhibitors.  This finding led to the inclusion of a black-box warning in the product’s prescribing information, and limited the 10 mg dose to certain patients who are not treated effectively or who experience severe side effects with other medications.

The clinical trial is now complete, and FDA is warning the public that preliminary results from safety clinical trial show a higher occurrence of serious heart-related problems and cancer in RA patients treated with both the 5 mg and 10 mg strengths of tofacitinib as compared to TNF inhibitors.  The study also investigated other potential risks including blood clots in the lungs and death.  FDA is awaiting final results related to all of the safety concerns.

For additional information, please review FDA’s Drug Safety Communications dated February 25, 2019 (here, July 26, 2019 (here ), and yesterday’s February 4, 2021 communication (here). Stay tuned for FDA’s decision on what further actions the Agency and the manufacturer may take.