Patients With AxSpa Receive Some Benefit From JAKs

The Janus kinase (JAK) inhibitors tofacitinib, upadacitinib, and filgotinib have shown improvement in some major disease domains in patients with axial spondyloarthritis (axSpa), but their performance in domains involving enthesitis or uveitis has been less convincing, according to a review article published online in the International Journal of Molecular Sciences.

“Further studies are needed in patients who have not responded adequately to anti-tumor necrosis factor-α and/or anti-interleukin-17 biologics to better understand in which line of treatment these drugs should be optimally used,” advised corresponding author Marino Paroli, MD, of Sapienza University of Rome in Italy, and coauthors.

Introduced as a therapeutic option for patients with rheumatoid arthritis more than a decade ago, JAK inhibitors are now used in the management of additional inflammatory rheumatic diseases. The review article focused on their efficacy and safety in patients with axSpa.

Published studies of tofacitinib, upadacitinib, and filgotinib have demonstrated patient gains on a slate of important measures, including Assessment in Ankylosing Spondylitis (ASAS) 20% and 40% response, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Patients’ quality of life and fatigue also improved. The authors detailed specifics on the reported efficacy in the SELECT-AXIS 1, SELECT-AXIS 2, and TORTUGA trials, which together spanned patients with both radiographic and nonradiographic axSpa.

Even so, safety concerns remain, according to the review. The US Food and Drug Administration requires a black box warning for JAK inhibitors that treat rheumatoid arthritis and other inflammatory diseases, citing an increased risk of serious cardiovascular events, neoplasia, and thrombosis.

“Despite all these important considerations and the need for future large randomized controlled trials,” the authors wrote, “JAK inhibitors represent, to date, an innovative therapy for the treatment of patients with AxSpa who have failed all other available treatments.”

Reference
Paroli M, Caccavale R, Paroli MP, Spadea L, Accapezzato D. Janus kinase inhibitors: a new tool for the treatment of axial spondyloarthritis. Int J Mol Sci. 2023;24(2):1027. doi:10.3390/ijms24021027