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REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1488357
This article is part of the Research Topic Autoinflammatory novelties: from pathogenic mechanisms to clinical and therapeutic implications View all 3 articles
JAK inhibition and axial Spondyloarthritis: new steps on the path to understanding pathophysiology
Provisionally accepted
Francesco Ciccia 1
Dennis McGonagle 2,3,4
Ranjeny Thomas 5
Helena Marzo-Ortega 2,3,4
David A. Martin 6
Arne Yndestad 7*
Mikhail Volkov 8
Obed Nimley 9- 1 Dipartimento di Medicina di Precisione, Università della Campania L. Vanvitelli, Naples, Campania, Italy
- 2 Leeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, England, United Kingdom
- 3 Leeds Biomedical Research Centre (NIHR), Leeds, United Kingdom
- 4 Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
- 5 Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia
- 6 Pfizer Inc, Cambridge, MA, United States
- 7 Pfizer Inc, Oslo, Norway
- 8 Pfizer BV, Capelle aan den IJssel, Netherlands
- 9 IPG Health Med Coms Inc, Parsippany, NJ, United States
Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease that predominantly affects the sacroiliac joints and spine. TNF and IL-17A are key cytokines in disease pathogenesis and are established axSpA treatment targets. Recently, axSpA treatment options have been complemented by Janus kinase inhibitors (JAKi), which inhibit various cytokines without directly impacting TNF or IL-17 signaling. The effect of JAKi on axSpA remains under investigation: besides a JAK2-mediated (and potentially tyrosine kinase 2 [TYK2]-mediated) effect on the IL-23/IL-17 axis, emerging evidence suggests γδ T cells, type 3 innate lymphoid cells, and mucosa-associated invariant T cells, which are dependent on IL-7 and/or IL-15 and thus on JAK1, are strongly inhibited by JAKi used to treat axSpA. This review summarizes potential effects of JAKi on axSpA and shows evidence from pre-clinical/clinical studies.Greater understanding of the mechanisms of action of available treatments may improve knowledge of axSpA and pave the road for future therapies.
Keywords: Axial spondyloarthritis, Gut-joint axis, JAK-STAT pathway, Janus kinase inhibitor, pathophysiology
Received: 29 Aug 2024; Accepted: 13 Feb 2025.
Copyright: © 2025 Ciccia, McGonagle, Thomas, Marzo-Ortega, Martin, Yndestad, Volkov and Nimley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Arne Yndestad, Pfizer Inc, Oslo, Norway
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.