The Use of Janus Kinase Inhibitors in Axial Spondyloarthritis: Current Insights

Abstract

Current pharmacological treatments of axial spondyloarthritis (axSpA) are limited to non-steroidal anti-inflammatory drugs (NSAIDs) and biological agents, including TNFα inhibitors and IL-17 inhibitors. Despite the availability of these agents, many patients either fail to respond adequately, lose their initial therapeutic response over time, or develop undesirable side effects, thus highlighting the need for new treatment options. Janus kinase (JAK) and signal transducers and activators of transcription (STAT) are a group of intracellular kinases that play a role in the signaling pathway induced by cytokines and certain growth factors associated with the inflammatory process of axSpA. There are several lines of evidence implicating the JAK–STAT pathway in the pathophysiological process of axSpA, including genetic data, the use of certain JAK in the intracellular signal of specific cytokines involved in axSpA (IL-23, IL-22, and IL-6), and data from experimental models of SpA. This provides a rationale for the assessment of JAK inhibitors (JAKi) in clinical trials with patients with axSpA. In this review, we examine the role of JAK–STAT signaling in the pathogenesis of axSpA and summarize the results from recent clinical trials of JAKi (tofacitinib, upadacitinib, and filgotinib) in patients with axSpA.

Janus Kinase Inhibitors: A New Tool for the Treatment of Axial Spondyloarthritis

“…Although the use of these new drugs has greatly improved the quality of life of patients and can slow the radiological progression of the disease, a significant number of subjects do not respond or partially respond to therapy. Therefore, the availability of new drugs for these difficult-to-treat patients is urgently needed [ 9 , 10 ]. In recent years, thanks to intensive research in rheumatic diseases, a new class of drugs called Janus kinase inhibitors (JAKinibs) have become available.…”

Emerging story of gut dysbiosis in spondyloarthropathy: From gastrointestinal inflammation to spondyloarthritis

“…The IL-17 axis has a great deal of promise in terms of enhancing SpA therapy options (Smith and Colbert, 2014), and the potential role of gut dysbiosis can be considered. tsDMARDs tsDMARDs, such as Janus kinase (JAK) inhibitors, have begun to be used in clinical trials with promising outcomes (Gladman et al, 2017;Toussirot, 2022). There have been limited studies of longitudinal changes in the gut microbiome with tsDMARD treatment in SpA.…”

“…tsDMARDs, such as Janus kinase (JAK) inhibitors, have begun to be used in clinical trials with promising outcomes ( Gladman et al., 2017 ; Toussirot, 2022 ). There have been limited studies of longitudinal changes in the gut microbiome with tsDMARD treatment in SpA.…”

Geschichte der reaktiven Arthritis. Historische Meilensteine und Zukunft

“…Erforderlich sind auch weiterführende kontrollierte Therapiestudien, die, ausgehend von den jüngsten Erfahrungen zur Wirksamkeit einer antibiotischen Kombinationstherapie und von Biologika bei chronischer ReA, eine validierte Therapieempfehlung ermöglichen. Die erfolgreiche Therapie der axialen SpA mit Januskinaseinhibitoren könnte auch eine Option für die Therapie der chronischen ReA sein [52,53].…”