JAK inhibitors increase risk of cardiovascular problems and cancer, warns PRAC

Patients 65 years or older, those with increased risk of cardiovascular disorders like heart attack or stroke, individuals who smoke or have for an extended period in the past and those at increased risk of cancer should only be given Janus kinase (JAK) inhibitors if no other suitable treatment is available, recommends the European Medicines Agency (EMA)’s Pharmacovigilance Risk Assessment Committee (PRAC).

The committee advises that Cibinqo (abrocitinib), Jyseleca (filgotinib), Olumiant (baricitinib), Rinvoq (upadacitinib) and Xeljanz (tofacitinib), used for chronic inflammatory conditions, should have limited distribution to minimise risk of serious side effects such as cardiovascular diseases, blood clots, cancer and serious infections.

Patients at risk of blood clots in the lungs and venous thromboembolism (VTE) should be cautious in considering JAK inhibitors. The group also recommended patients at risk of VTE, cancer or major cardiovascular problems should be offered a reduced dose.

The proposed restrictions are due to a review of available data, including clinical trial results for Xeljanz and initial findings from an observational study of Olumiant. The review established that Xeljanz increases risk of major cardiovascular condition such as cancer, VTE, serious infection and death due to any cause when compared to TNF-alpha inhibitors.

During the review, the PRAC took onboard advice from experts such as rheumatologists, dermatologists, gastroenterologists and patient representatives.

Conditions at increased risk of serious side effects with JAK inhibitors

The PRAC has confirmed that individuals with the following chronic inflammatory disorders should not take JAK inhibitors:

• Rheumatoid arthritis (RA)
• Psoriatic arthritis
• Juvenile idiopathic arthritis
• Axial spondyloarthritis
• Ulcerative colitis (UC)
• Atopic dermatitis
• Alopecia areata (AA).

The review did not evaluate JAK inhibitors Jakavi and Inrebic for myeloproliferative disorders, or safety concerns for short-term use of Olumiant for COVID-19, which is under assessment by the EMA.