New treatment targets for axial spondyloarthritis

Abstract

Axial spondyloarthritis (axSpA) patients can be divided into those with structural damage in the SI joint visible on X-rays, termed radiographic axSpA or AS, and those in an earlier phase of the disease, without structural damage in the SI joint, termed non-radiographic axSpA. TNF-blockers have been shown to be highly effective in the treatment of active axSpA. Interestingly, conventional DMARDs and also non-TNF-blocker biologics targeting IL-1, IL-6 and T cells (abatacept) are not effective. Recent interest has focused on the cytokines IL-23 and IL-17 as potential treatment targets in axSpA. An open-label trial with ustekinumab showed a good efficacy in AS patients. Two placebo-controlled phase 3 trials with a mAb blocking IL-17, secukinumab, showed a good reduction in disease activity, similar to that shown for TNF blockers. Probably triggered by inflammation, new bone formation is another hallmark in AS and a potentially important treatment target. However, a previously reported inhibitory effect of NSAID treatment could not be confirmed in a recent NSAID trial.

Keywords: IL-17–blockade; IL-23–blockade; ankylosing spondylitis; axial spondyloarthitis; biologics; small molecules.