The IL-23/IL-17A axis in spondyloarthritis: therapeutics informing pathogenesis?

To give an overview of the recently published trials relating to IL-23/IL-17 pathway in spondyloarthritis (SpA).

Recent studies in psoriasis confirmed the efficacy of targeting the IL-23/IL-17 pathway, with emerging evidence from head-to-head studies suggesting functional hierarchy of these inhibitors. In psoriatic arthritis (PsA), recent studies have indicated the efficacy of inhibiting IL-23p19, in addition to IL-23p40 and IL-17A, albeit all with lower hurdle results than those seen in psoriasis. The first head-to-head study of an IL-17A and tumour necrosis factor inhibitor in PsA has also recently been published. Recent studies have demonstrated the efficacy of the IL-17A inhibitor, ixekizumab, across the axial SpA spectrum. In contrast, inhibition of IL-12/IL-23p40 and IL-23p19 both failed in axial SpA. In inflammatory bowel disease (IBD), recent studies indicate efficacy of IL-23p40 and IL-23p19 inhibition, in contrast to the previous failed studies of IL-17 inhibition.

Clinical trials of IL-23/IL-17 inhibition have been transformative in psoriasis, with more mixed results in PsA and differential responses in axial SpA and IBD. These results pose challenges to our fundamental understanding of SpA pathogenesis and further head-to-head studies and more subtle evaluation of the local tissue-specific aspects will be required.