Targeting intracellular pathways in idiopathic inflammatory myopathies: A narrative review

Abstract

In recent decades, several pieces of evidence have drawn greater attention to the topic of innate immunity, in particular, interferon (IFN) and Interleukin 6 in the pathogenesis of idiopathic inflammatory myopathies (IIM). Both of these molecules transduce their signal through a receptor coupled with Janus kinases (JAK)/signal transducer and activator of transcription proteins (STAT). In this review, we discuss the role of the JAK/STAT pathway in IIM, evaluate a possible therapeutic role for JAK inhibitors in this group of diseases, focusing on those with the strongest IFN signature (dermatomyositis and antisynthetase syndrome).

Primary-Sjögren’s-Syndrome-Related Interstitial Lung Disease: A Clinical Review Discussing Current Controversies

“…Type 1 IFN signaling is mediated by the JAK-STAT pathway, whose modulation with the novel JAK-inhibitors has proved efficacious in different autoimmune diseases. Growing evidence indicates that JAK-STAT signaling is also involved in both pro-inflammatory and pro-fibrotic processes in ILD, and JAK-inhibitors are being successfully employed for the treatment of both COVID-19 disease and rapidly-progressive CTD-ILD [86][87][88][89][90]. Recently, a phase II RCT of Filgotinib (a Jak1-inhibitor) in pSS failed to reach its primary endpoint, consisting of a composite outcome measure; however, a sub-analysis of the trial showed a trend toward clinical efficacy in patients with severe disease [91].…”