Increased pulmonary embolism risk with high-dose tofacitinib

The European Medicines Agency (EMA) has issued new advice to healthcare professionals recommending that they do not exceed the recommended dosage of tofacitinib (Xeljanz) when treating patients with rheumatoid arthritis.

The advice follows the results of an ongoing clinical trial that has shown an increased risk of pulmonary embolism and all-cause mortality at a dosage of 10mg tofacitinib twice daily, ie twice the recommended dosage for rheumatoid arthritis and psoriatic arthritis of 5mg twice daily. The open-label post-marketing study is designed to compare the safety of two dosages of tofacitinib (5mg and 10mg twice daily) with the anti-TNF agents adalimumab and etanercept in patients aged 50 years and older with rheumatoid arthritis and at least one cardiovascular risk factor. The study has indicated an approximately five-fold higher incidence of pulmonary embolism in patients taking tofacitinib 10mg twice daily compared with patients taking an anti-TNF agent. Patients in the study on the higher dosage of tofacitinib have had their dose reduced for the remainder of the trial.

While the full results of the study are awaited, the EMA recommends that healthcare professionals should adhere to the authorised dosage of 5mg twice daily tofacitinib in patients with rheumatoid arthritis. Furthermore, all patients taking tofacitinib (regardless of indication) should be monitored for signs and symptoms of pulmonary embolism. Patients should seek immediate medical attention if they experience symptoms such as difficulty breathing, chest or upper back pain, coughing up blood, excessive sweating or bluish skin.

In response to this safety signal, a review of tofacitinib is being carried out by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) to consider if any regulatory action is needed.


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