Clinical Trials Supporting the Role of the IL-17/IL-23 Axis in Axial Spondyloarthritis

Front Immunol. 2021 Jun 2:12:622770. doi: 10.3389/fimmu.2021.622770. eCollection 2021.

Abstract

The term spondyloarthritis (SpA) encompasses a heterogeneous group of inflammatory musculoskeletal diseases with several common genetic background and clinical features, including the possible involvement of the axial skeleton with peripheral mono- or oligo- arthritis and frequently coexisting skin, eye and intestinal manifestations. When the sacroiliac joints or other parts of the spine or thoracic wall are predominantly affected at magnetic resonance or X-ray imaging with inflammatory back pain, the disease is classified as axial SpA and the therapeutic choices are significantly different compared to cases of peripheral arthritis. Moving from the narrow effectiveness and safety profiles of non-steroidal anti-inflammatory drugs, there has been a significant research effort aimed at identifying new treatments based on our better understanding of the pathogenesis of SpA. Indeed, in parallel with the solid data demonstrating that IL-17 and IL-23 are key cytokines in the development of enthesitis and spondylitis, monoclonal antibodies interfering with this pathway have been developed for the treatment of axial SpA. Furthermore, the IL-17/IL-23 axis is key to extra-articular manifestations such as inflammatory bowel disease, uveitis, and psoriasis which are frequent comorbidities of SpA. Currently available drugs act through these mechanisms recognizing IL-23 and targeting IL-17, such as secukinumab and ixekizumab. These therapeutic approaches are now envisioned in the international treatment recommendations for psoriatic arthritis with an axial phenotype as well as for ankylosing spondylitis (AS). We will provide herein a concise comprehensive overview of the clinical evidence supporting the use of these and other drugs acting on IL-23 and IL-17 in axial SpA.

Keywords: HLA B27 allele; Th17; biologics; enthesitis; spondylitis.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Clinical Trials as Topic*
  • Evidence-Based Medicine
  • Humans
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / metabolism
  • Interleukin-23 Subunit p19 / antagonists & inhibitors*
  • Interleukin-23 Subunit p19 / metabolism
  • Signal Transduction
  • Spondylarthritis / diagnosis
  • Spondylarthritis / drug therapy*
  • Spondylarthritis / immunology
  • Spondylarthritis / metabolism
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • IL17A protein, human
  • IL17F protein, human
  • IL23A protein, human
  • Interleukin-17
  • Interleukin-23 Subunit p19