EMA Puts Temporary Restrictions on Tofacitinib Due to PE Risk

Megan Brooks

May 17, 2019

The European Medicines Agency's (EMA's) Pharmacovigilance Risk Assessment Committee (PRAC) is temporarily advising physicians not to prescribe the 10-mg twice-daily dose of tofacitinib (Xeljanz, Pfizer) to patients at high risk for pulmonary embolism (PE).

These include patients with heart failure, cancer, inherited coagulation disorders, a history of venous thromboembolism, either deep venous thrombosis (DVT) or PE, as well as patients taking combined hormonal contraceptives or hormone replacement therapy or who are scheduled to have major surgery.

Prescribers should also consider other factors that may increase the risk for PE, including age, obesity, smoking, or immobilization, the EMA said in a news release.

The recommendation stems from results of an ongoing postmarketing study that is evaluating the safety of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily in comparison with a tumor necrosis factor (TNF) inhibitor in patients with rheumatoid arthritis (RA) aged 50 years or older who have one or more cardiovascular risk factors.

Preliminary results found 19 cases of PE in 3883 patient-years in the tofacitinib 10-mg twice-daily arm, compared with three cases in 3982 patient-years in the TNF-inhibitor arm. Additionally, there were 45 deaths from all causes in 3897 patient-years in the 10-mg twice-daily arm, compared with 25 deaths in 3982 patient-years in the TNF-inhibitor group.

In February, the US Food and Drug Administration flagged the same risk, as reported by Medscape Medical News.

Tofacitinib was first approved in Europe in 2017 for adults with moderate to severe RA. In 2018, it was approved in Europe for the treatment of psoriatic arthritis and severe ulcerative colitis. The approved dose for treating RA and psoriatic arthritis is 5 mg twice daily.

The EMA notes that because the 10-mg twice-daily dose is the only recommended starting dose for the treatment of ulcerative colitis, "patients with this condition who are at high risk of blood clots must not be started on Xeljanz. Patients at high risk currently taking this dose for any condition must be switched to alternative treatments."

The new recommendations are temporary and follow previous advice from the PRAC not to exceed the recommended 5-mg twice-daily dose in RA patients. The PRAC has launched an in-depth review of all available evidence and will provide updated guidance when their review is complete.

Patients who are receiving tofacitinib, irrespective of indication, should be monitored for the signs and symptoms of PE and be advised to seek medical attention immediately if they experience them.

A letter is being sent to all healthcare professionals in Europe who are expected to prescribe tofacitinib to inform them of the temporary treatment recommendations.

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