Blocking Interleukin-12 and Interleukin-23 in the Treatment of Axial Spondyloarthritis

Abstract

Currently, there are only two effective drug classes approved for treatment of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA): non-steroidal anti-inflammatory drugs (NSAIDs) and, if NSAIDs fail, tumour necrosis factor (TNF)-α blockers. Although the majority of patients do respond well to these treatment options, there is certainly an unmet need for further therapeutic options for patients who do not respond to, do not tolerate or have contraindications for NSAIDs and TNF-α blockers. Blockade of the Th17 pathway that includes inhibition of interleukins (IL)-12/23 and to a further extent IL-17 represent currently the most promising therapeutic targets in axSpA. The first positive results on the blockade of IL-12/23 in active AS should be confirmed in larger placebo-controlled studies, ideally including the entire population of axSpA. It is very important to identify whether IL-12/23 and IL-17 blockade also works in TNF-α blocker non-responders and if there are specific predictors of response to one or another drug class. Also, effects of this therapy on long-term outcomes including progression of structural damage in the spine in AS/axSpA are of high importance and should be evaluated.