The role of ixekizumab in the treatment of nonradiographic axial spondyloarthritis

Abstract

Nonradiographic axial spondyloarthritis (nr-axSpA) is a subtype of SpA with undeveloped definite radiographic sacroiliitis. Tumor necrosis factor inhibitors have demonstrated effectiveness in nr-axSpA patients who do not respond to first-line therapy. More recently, accumulated data from genetic, experimental, and clinical studies revealed that IL-17 is a key player in the pathogenesis of SpA, leading to development of new biologics directly inhibiting IL-17. Among them, ixekizumab is a high-affinity monoclonal antibody that selectively targets IL-17A and has exhibited significant efficacy and acceptable safety profiles in the treatment of nr-axSpA. The aim of this paper is to narratively review the recent insights of IL-17 in the pathogenesis of axSpA and discuss the effectiveness and safety of ixekizumab in treatment of nr-axSpA.

Plain language summary

Nonradiographic axial spondyloarthritis (Nr-axSpA) is a type of inflammatory disease affecting the spine, particularly the sacroiliac joints, where x-rays don't clearly show signs of damage. When initial treatments don't work, medications like tumor necrosis factor inhibitors can help. But now, recent studies have found that IL-17 plays a big role in this condition. Because of this, new drugs targeting IL-17, such as ixekizumab, have been developed. Ixekizumab is a powerful medication that specifically targets IL-17A. Studies have found it to be both effective and safe in treating nr-axSpA. This article aims to explain how IL-17 contributes to this condition and discuss how ixekizumab can help people with nr-axSpA.

Graphical abstract

Executive summary

Background

• Nonradiographic axial spondyloarthritis (nr-axSpA) is a classification term covering patients with axSpA without definite radiographic sacroillitis.

• Patients with nr-axSpA can exhibit comparable disease burden and functional impairment compared with patients with radiographic axSpA (r-axSpA).

The role of IL-17 in the pathogenesis of axial spondyloarthritis

• IL-17 plays a pivotal role in host protection and inflammation.

• Genetic, experimental, and clinical studies have revealed that IL-17 is one of the key players in the pathogenesis of SpA including inflammation and pathogenic bone remodeling, leading to development of new biologics directly inhibiting IL-17.

Clinical trials of ixekizumab in patients with nr-axSpA

• Ixekizumab, a high-affinity IL-17A monoclonal antibody, has exhibited efficacy in both biologic-naive and TNF inhibitor-exposed patients with r-axSpA.

• More recently, the COAST-X, a 52-week, randomized, double-blind, placebo-controlled, parallel-group, phase III trial, showed that ixekizumab can be effective and safe option also for treating nr-axSpA.

• Ixekizumab has shown an acceptable safety profile, notably in tuberculosis, which is the one of the major safety issues in treatment with TNF inhibitors.

Conclusion

• IL-17 inhibitors including ixekizumab may be preferred in SpA patients with significant psoriasis while TNF monoclonal antibodies are preferred for uveitis or inflammatory bowel disease.

Keywords: :

• biologics
• IL-17 inhibitor
• ixekizumab
• nonradiographic axial spondyloarthritis
• spondyloarthritis

Financial disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

Figure 1 was created with BIoRender.com.