Novel therapies for axial spondyloarthritis and future directions

Abstract

This update explores emerging therapeutic strategies aimed at novel targets implicated in the pathogenesis of axSpA. Recent clinical trials of bimekizumab, a monoclonal antibody targeting both IL-17A and IL-17F, and janus-kinase inhibitors have demonstrated significant and sustained improvements in clinical and imaging outcomes, with a favorable safety profile and reduced rates of uveitis. Investigational agents targeting GM-CSF and MK2 have not demonstrated efficacy, but the targeting of autoreactive T cell clonotypes shared among individuals with axSpA using depleting antibodies to the variable gene segment 9 of the T cell receptor beta chain appears promising. Preclinical investigation has focused on cytokines, such as macrophage inflammatory protein, and kinases, such as mammalian target of rapamycin and phosphoinositide 3-kinase, and transcriptional factors, such as retinoic acid receptor-related orphan receptor-yt that regulate expression of IL-17A and -F cytokines. Several advances in therapeutic technologies also hold promise for more effective therapeutics based on current targets.

Keywords: Axial spondyloarthritis; Bimekizumab; Biologic therapies; Filgotinib; IL-17A; IL-17F; Janus kinase inhibitors; T cell receptor clonotypes; Upadacitinib.