IL-17 inhibition in axial spondyloarthritis: current and future perspectives

ABSTRACT

Introduction: Interleukin (IL)-17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) as well as of other spondyloarthritides. There is a number of substances targeting IL-17, which are at different stages of development in the axSpA indication.

Areas covered: This review summarizes the current evidence on the role of IL-17 in the pathophysiology of axSpA and provided a comprehensive review of clinical and radiographic outcomes as well as of safety data from studies with IL-17A inhibitors secukinumab and ixekizumab. Ongoing studies on other IL-17 inhibitors (bimekizumab, brodalumab and BCD-085) that are being developed are also summarized.

Expert opinion: The development of the IL-17 inhibitors has expanded AS treatment with effective options and confirmed the pathophysiological role of IL-17 in axSpA. IL-17 inhibition showed sufficient efficacy against signs and symptoms of the disease even after the failure of tumor necrosis factor inhibitors, being at the same time reasonably safe.

KEYWORDS:

• Ankylosing spondylitis
• axial spondyloarthritis
• bimekizumab
• brodalumab
• interleukin 17
• ixekizumab
• netakimab
• secukinumab

Article highlights

• IL-17 plays a major role in pathophysiology of axSpA.

• Data from clinical trials confirmed the high anti-inflammatory potential of IL-17 blockade in axSpA.

• The spectrum of drugs targeting IL-17 will expand in the next few years including IL-17A blockers ixekizumab and BCD-085 (netakimab), IL17A and F inhibitor bimekizumab, and IL-17RA blocker brodalumab.

• Head-to-head trials comparing TNFi with IL-17 inhibitors are required in order to define the optimal place of IL-17 blockade in the treatment algorithm of axSpA.

• Whether IL-17 blockade is effective in prevention or retardation of radiographic spinal progression in axSpA is another important research question to be answered in prospective trials.

This box summarizes the key points contained in the article.

Declaration of interest

D Poddubnyy has received grant/research support from AbbVie, MSD, Pfizer, and Novartis; has been a speaker/consultant for AbbVie, BMS, Janssen, Lilly, Celgene, MSD, Novartis, Pfizer, Roche, and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.