Pfizer, Inc. has altered an important clinical trial involving Xeljanz, after an early analysis suggested rheumatoid arthritis (RA) patients on a higher-dosing regimen were more likely to experience pulmonary embolism.
The U.S. Food & Drug Administration (FDA) approved the 5mg twice-daily dose of Xeljanz (tofactinib) to treat RA in 2012. At the time, however, the agency also ordered Pfizer to study the occurrence of certain adverse events associated with two Xeljanz dosing regimens (5 mg twice daily and 10 mg daily) in combination with metformin versus those taking a tumor necrosis factor inhibitor (TNFi).
Pfizer subsequently designed clinical trial A3921133 to evaluate heart-related adverse events. Unlike other post-market trials involving Xeljanz, the company required participants to be at least 50 years old and have one cardiovascular risk factor.
The Rheumatology Data Safety Monitoring Board recently notified Pfizer that study subjects taking the 10 mg Xeljanz dose “had a statistically and clinically important difference in the occurrence of pulmonary embolism” compared with those receiving a TNFi. The 10 mg group also had a higher death rate compared to those taking the 5 mg twice daily dose.
Because of these findings, all patients enrolled in the trial’s 10mg twice daily Xeljanz arm will be transitioned to the lower dose regimen. The study will continue and is expected to conclude later this year.
The FDA is working with Pfizer to evaluate other currently available safety information for Xeljanz and will update the public with any new information based on its ongoing review.
In the meantime, the agency urged healthcare providers to follow all dosage recommendations when prescribing Xeljanze. The FDA has not approved the 10 mg twice daily regimen to treat RA. In fact, the higher dose is only indicated to treat ulcerative colitis.
Xeljanz patients should seek medical attention if they experience any symptoms that may be associated with a pulmonary embolism:
Finally, they should not stop taking Xeljanz or lower their dose without first talking to their doctor.