[Baricitinib image courtesy of PubChem]
The European Medicines Agency (EMA) is backing a series of measures to reduce the risk of serious side effects associated with Janus kinase (JAK) inhibitors, limiting their use in high-risk individuals.
Similarly, Health Canada is recommending updated labeling for the drug class to disclose the risk of serious cardiovascular events and cancer. The agency is working with Novartis (NYSE:NVS) to update Jakavi’s (ruxolitinib) labeling. Health Canada has already worked with manufacturers to update the labeling for the JAK drugs Cibinqo (abrocitinib), Inrebic (fedratinib), Olumiant (baricitinib,), Rinvoq (upadacitinib) and Xeljanz/Xeljanz XR (tofacitinib).
In 2021, FDA announced that it would require a warning for JAK inhibitors, indicating that they may lead to an elevated risk of cardiovascular events, cancer, blood clots and death.
Health Canada recommended labeling changes after reviewing a thorough safety review. It identified reports of serious heart-related events, fatal blood clots and cancer in JAK inhibitor recipients in 2020 and 2021.
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that JAK inhibitors be prescribed only when no suitable alternatives exist for several high-risk groups. Those include individuals 65 and older, individuals with an elevated risk of major cardiovascular problems, smokers and those with elevated cancer risk.
PRAC also urged caution in prescribing JAK inhibitors to individuals with risk factors for blood clots in the lungs and venous thromboembolism.
The committee consulted with an outside group of physicians and patient representatives to reach its conclusions.
A study recently published in BMJ focusing on rheumatoid arthritis patients taking either JAK inhibitors versus adalimumab presented “reassuring data” about the risks of major adverse cardiovascular events and venous thromboembolism events in patients initiating a JAKi compared to adalimumab. The assessment included data from patients with a high risk of cardiovascular diseases.
Earlier studies had found elevated risk of cardiovascular events associated with JAK inhibitor use.
In 2018, Austrian researchers linked JAK inhibitors to aggressive lymphomas in a small number of patients with myelofibrosis.
Since 2011, roughly a dozen JAK inhibitors have won regulatory approval worldwide.