JAK inhibitors and black box warnings: what is the future for JAK inhibitors?

Janus kinase inhibitors (JAKi) have dramatically improved the treatment of various autoimmune and myeloproliferative disorders. Recently, concern has arisen regarding their safety in patients with rheumatoid arthritis.Here, we provide a comprehensive summary of the major current and emerging JAKi and their indications, address recent studies on comparative safety, and provide insight into their future and use. We emphasize that the application of the research findings on a case-by-case basis should consider a patient's age, comorbidities, disease for which JAKi is being considered, disease activity, the JAKi target(s), alternate treatment options available for the patient, and the planned duration of JAKi.Rheumatologists are used to prescribing therapies in which a risk-to-benefit assessment is required as well as to screening and monitoring the safety of medications. Thus, rheumatologists are already practiced in applying specific criteria to effectively screen and monitor patients who are candidates for JAKi therapy. Ongoing research will help to clarify any mechanisms underlying differential safety signals between JAK and other therapies, what the balance between risk and efficacy is, who the susceptible subpopulations are, and whether safety signals are shared between different JAKis and across indications.