A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition.

Spondyloarthritis (SpA) comprises a group of chronic inflammatory diseases with overlapping clinical, genetic and pathophysiological features including back pain, peripheral arthritis, psoriasis, enthesitis, and dactylitis. Several cytokines are involved in the pathogenesis of SpA, variously contributing to each clinical manifestation. Many SpA-associated cytokines, including interleukin (IL)-23, IL-17, IL-6, type I/II interferon, and tumour necrosis factor signal directly or indirectly via the Janus kinase (JAK)-signal transducer and activator of transcription pathway. JAK signalling also regulates development and maturation of cells of the innate and adaptive immune systems. Accordingly, disruption of this signalling pathway by small molecule oral JAK inhibitors can inhibit signalling implicated in SpA pathogenesis. Herein we discuss the role of JAK signalling in the pathogenesis of SpA and summarise the safety and efficacy of JAK inhibition via reference to relevant SpA clinical trials.