New treatment options and emerging drugs for axial spondyloarthritis: biological and targeted synthetic agents

ABSTRACT

Introduction: Ankylosing spondylitis (AS) and axial spondyloarthritis (ax SpA) are chronic inflammatory diseases mainly involving the axial skeleton. Pharmacological treatments for AS and ax SpA usually include local glucocorticoid injections, NSAIDs and anti-TNFα agents. Since around 30% to 40% of patients are non responders or intolerant to anti-TNFα agents, we need new therapeutic options for AS and ax SpA.

Areas covered: This review describes the new biological agents that can be used or are in development for AS or ax SpA as well as emerging synthetic targeted drugs.

Expert opinion: Based on the rationale of the involvement of the IL-23/Th17 axis in AS, novel biological agents have been developed and include secukinumab, an anti-IL-17A agent and ustekinumab, an anti-IL-23 antibody. New compounds in the class of synthetic drugs are apremilast, a PDE4 inhibitor, and inhibitors of kinase pathways. Secukinumab gave positive results in the treatment of AS. Ustekinumab yielded promising results in AS in an open labeled study. Apremilast is not effective in AS while results with kinase inhibitors are preliminary. Future studies will clarify the place of secukinumab in the therapeutic management of AS, its influence on radiographic progression and its effects on the non radiographic form of the disease.

KEYWORDS:

• Axial spondyloarthritis
• IL-23
• Th17
• secukinumab
• ustekinumab
• apremilast

Article highlights

• Around 30% to 40% of patients are non-responders or intolerant to anti-TNFα agents in AS and ax SpA

• Biological drugs other than than anti-TNFα (including anti IL-1, anti-CD20, anti-IL6 agents and the inhibitor of costimulatory pathway CTLA-4 Ig) that are used in RA are ineffective in AS and ax SpA.

• There is a strong rationale for targeting the IL-23/Th17 pathway in AS and ax SpA

• Secukinumab, an anti-IL-17A agent demonstrated its efficacy in both anti TNFα naïve and anti TNFα non responder AS patients in the MEASURE program.

• Ustekinumab is licensed for the treatment of psoriasis and psoriatic arthritis. Results of an open label study of ustekinumab in AS are encouraging, giving the rationale for a phase III study

• Apremilast a targeted synthetic drug and phosdiesterase-4 inhibitor is not effective in AS.

• Tofacitinib, a JAK inhibitor used in RA gave promising results in a phase II/III study in AS, but its development is interrupted.

This box summarizes key points contained in the article.

Acknowledgments

Language editing services, provided by Thivet Frances, Thivet Language Services, were utilized in the production of this paper.

Declaration of interest

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

Additional information

Funding

This paper was not funded.