Evolving landscape of JAK-STAT inhibition in the treatment of immune-mediated inflammatory diseases.

Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) comprise a direct membrane-to-nucleus intracellular signaling pathway, facilitating rapid transcriptional changes in response to cytokines, growth factors, and hormones. Since the first JAK inhibitor (JAKi) gained regulatory approval in 2011, targeting of the JAK-STAT pathway has expanded significantly, with over a dozen approved agents and new indications in many immune-mediated inflammatory diseases. Newer agents targeting the JAK-STAT pathway have been developed with improved JAK selectivity, delivery to specific tissues, and new mechanisms of action in an effort to improve efficacy and address ongoing safety concerns. This review covers the expanding clinical use of JAK-STAT inhibition across immune-mediated inflammatory diseases as well as new therapeutic strategies and approaches.