EMA issues new guidance to limit use of JAK inhibitors for chronic inflammatory disorders

The European Medicines Agency’s (EMA) safety committee has recommended that the use of Janus kinase (JAK) inhibitors for several chronic inflammatory disorders should be limited over concerns of serious side effects.

Specifically, the committee recommended that these medicines should not be used to treat those aged 65 years and above, those at an increased risk of major cardiovascular problems, those who smoke or have in the past and those at an increased risk of cancer, unless no suitable treatment alternatives are available.

The committee also recommended using JAK inhibitors ‘with caution’ in patients with risk factors for blood clots in lungs and in deep veins, and that the doses should be reduced in some patient groups who may be at risk of venous thromboembolism (VTE), cancer or major cardiovascular problems.

The new guidance follows a review of available data, which was initiated at the request of the European Commission (EC). This included final results from a clinical trial of Xeljanz (tofacitinib), as well as preliminary findings from an observational study involving Olumiant (baricitinib).

The review, which involved advice from an expert group of rheumatologists, dermatologists, gastroenterologists and patient representatives, confirmed that Xeljanz increases the risk of major cardiovascular problems, cancer, VTE, serious infections and death due to any cause when compared with TNF-alpha inhibitors.

It has now been concluded that these safety findings apply to all approved uses of JAK inhibitors in chronic inflammatory disorders – rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, ulcerative colitis, atopic dermatitis and alopecia areata.

The EMA outlined that the product information for JAK inhibitors for these indications will be updated with new recommendations and warnings. This includes Cibinqo (abrocitinib), Jyseleca (filgotinib), Olumiant (baricitinib), Rinvoq (upadacitinib) and Xeljanz (tofacitinib).

Education materials for patients and healthcare professionals will also be revised accordingly, the organisation said.

The recommendations will now be sent to the Committee for Medicinal Products for Human Use, which will issue a final legally binding decision applicable in all EU Member States.

The JAK inhibitors Jakavi and Inrebic, which are used to treat myeloproliferative disorders, were not included in the review. The use of Olumiant in the short-term treatment of COVID-19, which is under assessment by EMA, was also not covered in the review.