FDA Drug Safety Communication: Initial safety trial results find increased risk of serious heart-related problems and cancer with tofacitinib

The initial results of a completed safety clinical trial show a higher occurrence of serious heart-related problems and cancer in patients with rheumatoid arthritis treated with tofacitinib (both 5mg BD and 10mg BD) compared to those treated with a TNF inhibitor.

SPS commentary:

This study was required by the FDA when it first approved tofacitinib, to evaluate the risk of serious heart-related events, cancer and infections in patients with rheumatoid arthritis aged >50 and with at least one CV risk factor, who were also taking methotrexate. Interim results from this study were communicated in 2019, showing an increased risk of blood clots and death with the higher dose (10mg BD), and at that time the US FDA approved a Boxed Warning. The study is now complete, with initial results showing an increased risk of serious heart-related problems and cancer with both evaluated doses. The final results for other safety endpoints are not yet available, and the FDA’s final conclusions and recommendations will be communicated in due course.  In the meantime, healthcare professionals are urged to consider the benefits and risks of tofacitinib when deciding whether to prescribe or continue patients on the medicine.

In 2019, the MHRA advised healthcare professionals of the potential risk of venous thromboembolism, and temporary contraindications for the 10mg twice-daily dose of tofacitinib in patients with risk factors for pulmonary embolism, following the interim results of the safety study. Following the conclusions of a European review, a number of final measures were introduced, which are summarised in a Drug Safety Update article published in March 2020.


US Food and Drug Administration

Resource links:

Drug Safety Update – summary of measures taken to minimise risk of venous thromboembolism and serious and fatal infections