Researchers looking into the link between Xeljanz and life-threatening blood clots say additional data is needed to better understand the safety signals that recently prompted an update to the drug’s Black Box Warning.
The U.S. Food & Drug Administration (FDA) first approved Xeljanz (tofactinib) at a 5mg twice-daily dose to treat rheumatoid arthritis (RA) in 2012. Five years later, the agency cleared the same dosing regimen for psoriatic arthritis, while a 10mg twice-daily dose was approved for ulcerative colitis in 2018.
In 2012, the FDA also ordered Pfizer to conduct a post-market study comparing the rate of certain adverse events in patients prescribed the 10mg twice-daily Xeljanz regimen and those being treated with either the 5 mg twice-daily protocol or a tumor necrosis factors (TNFi). To evaluate the risk of heart related events among these three group, Pfizer launched clinical trial A3921133. Unlike other Xeljanz post-market trials, the company required participants to be at least 50 years old and have one cardiovascular risk factor.
Earlier this year, Pfizer disclosed that preliminary findings from A3921133 suggested patients in the study’s 10mg twice-daily Xeljanz arm were 5-times more likely to suffer a pulmonary embolism compared to those taking a TNFi, and 3-times more likely compared to those on the 5mg twice-daily Xeljanz protocol. The higher-dose Xeljanz group also had more deaths from all causes compared to the study’s other patient groups.
In July, the FDA ordered Pfizer to update the Xeljanz Black Box Warning to reflect these findings. The agency also limited the approved use of Xeljanz for ulcerative colitis to patients who are not treated effectively or who experience severe side effects with certain other medicines. In such cases, doctors should prescribe the lowest effective dose possible and limit the 10mg twice-daily regimen to the shortest duration possible.
Recently, researchers at the American College of Gastroenterology Annual Meeting reported that a post hoc analysis evaluating the safety of Xeljanz in ulcerative colitis revealed comparable incidence rates of pulmonary embolism and deep vein thrombosis in patients who did and did not receive the agent.
But they acknowledged that their study sample was small and urged attendees not to overinterpret their findings.
“The incidence rates for DVT and PE were comparable with those that you would see in ulcerative colitis among people who do not take tofacitinib, but we really need more data about this,” William J. Sandborn, MD, director of the inflammatory bowel disease center at University of California, San Diego Health, concluded. “I refer all of you to the revised prescribing information that requires you to make an attempt to move patients from 10 mg to 5 mg during the maintenance period … in order to optimize the risk-benefit of this drug.