Recent FDA Safety Updates for JAK Inhibitors
The FDA added a Boxed Warning to all JAK inhibitors, including Xeljanz (tofacitinib), Olumiant (baricitinib), Rinvoq (upadacitinib), and Zeposia (ozanimod), in September 2021. This followed the ORAL Surveillance trial, which showed higher risks of serious heart-related events, cancer, blood clots, and death compared to TNF blockers in rheumatoid arthritis patients aged 50+ with at least one cardiovascular risk factor.[1][2]
What Risks Are Now Highlighted?
The warning flags:
- Major adverse cardiovascular events (MACE), like heart attack and stroke.
- Malignancies, especially lung cancer, lymphoma, and melanoma.
- Thrombosis, including pulmonary embolism, deep vein thrombosis, and arterial thrombosis.
- Overall mortality increase.
These risks were dose-dependent for Xeljanz (5 mg vs. 10 mg twice daily) and appeared early in treatment.[1]
Who Faces the Highest Risks?
Patients over 50 with cardiovascular risk factors (smoking, high blood pressure, high cholesterol) saw the most issues in trials. The FDA recommends these patients start with lower doses and use JAK inhibitors only if TNF blockers or other biologics fail. Younger patients or those without risks have less clear data.[2][3]
How Does This Affect Xeljanz Specifically?
Xeljanz carries the strongest evidence from ORAL Surveillance (4,362 patients). Real-world risks may vary, but prescribers must discuss these with patients via a medication guide. No changes to approved uses, but monitoring for symptoms like chest pain, shortness of breath, or leg swelling is now emphasized.[1][4]
Changes for Other Conditions and Drugs
For ulcerative colitis or psoriatic arthritis (Xeljanz approvals), similar precautions apply despite less trial data in those groups. Rinvoq and Olumiant got identical warnings post-approval based on shared class effects. Zeposia, mainly for MS, shares the label due to mechanism overlap.[2]
What Do Doctors and Patients Need to Do?
- Reserve for TNF failures; consider lowest effective dose.
- Screen for CV risks and smoking before starting.
- Watch for early warning signs; report to FDA MedWatch.
Patient concerns often focus on long-term cancer risk—studies show 1-2 extra cases per 1,000 patient-years vs. TNFs.[3][5]
Ongoing Studies and Future Updates
Post-marketing trials continue for younger patients and other indications. EMA issued similar warnings in 2022. No new Boxed Warnings since, but label updates track emerging data.[2]
Sources
[1]: FDA Drug Safety Communication: Safety Trial Finds Risk of Blood Clots
[2]: FDA Xeljanz Label Update
[3]: NEJM: ORAL Surveillance Trial Results
[4]: Pfizer Xeljanz Safety Info
[5]: DrugPatentWatch: JAK Inhibitor Patents and Litigation