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

ABSTRACTIntroduction 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.Areas covered 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.Expert opinion 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.KEYWORDS: Cancercomparative safetyJAK inhibitorsMACErheumatoid arthritisshared decision makingTnfi Article highlights Recently, several studies have been published on the comparative safety of Janus kinase inhibitors (JAKi) including the ORAL surveillance clinical trial.Much of the evidence to date points to an increased risk of herpes zoster from use of JAKi relative to other comparators and the risk can be minimized with vaccinations.There is an urgent need of long-term comparative safety studies evaluating the risk of MACE and malignancy among users of various JAKi drugs.Other important considerations in managing MACE, VTE, or cancer risks need to include minimizing inflammatory disease burden, decreasing exposure to glucocorticoids or NSAIDs, and smoking cessation.One of the most important issues raised by the ORAL Surveillance trial is how to effectively communicate risk to patient in a way that balances the risks and benefits of alternate therapies and the risk of undertreating disease.Declaration of interestJ Giles serves as consultant for Pfizer, AbbVie, Eli Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingN Singh is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number K23AR079588.