Emerging therapies for the treatment of spondyloarthritides with focus on axial spondyloarthritis

ABSTRACT

Introduction

Spondyloarthritides (SpA) such as axial spondyloarthritis (axSpA) including ankylosing spondylitis (AS) and psoriatic arthritis (PsA) including psoriasis are chronic immune-mediated disorders with involvement of tumor necrosis factor (TNF), interleukin (IL)-17 cytokines, and janus kinases (JAK) in their pathogenesis, with IL-23 clearly also playing a role in psoriasis, PsA, and chronic inflammatory bowel diseases.

Areas covered

In this narrative review, we focus on a biologic disease modifying anti-rheumatic drug (bDMARD), the bispecific IL-17A and IL-17 F inhibitor bimekizumab, and a targeted synthetic (ts) DMARD, the JAK inhibitor (i) filgotinib – emerging agents for the treatment of axSpA. Upadacitinib, another JAKi that has recently been reviewed intensively by us is already approved for axSpA and PsA in Europe.

Expert opinion

In contrast to inhibition of IL-17, JAKi also work in rheumatoid arthritis (RA), while agents inhibiting IL-17 are not, even though some effect may be there. Indeed, 4 JAKi including filgotinib are approved for RA. There are several head-to-head trials with bimekizumab in plaque psoriasis. The last one showed that the bispecific inhibition of IL-17A and IL-17 F with bimekizumab may indeed be superior to inhibition of IL-17A alone with 300 mg secukinumab (usual dosage). Whether this is also the case for treatment of axSpA and PsA remains to be shown.

KEYWORDS:

• IL-17 dual inhibition
• JAK inhibitors
• filgotinib
• bimekizumab
• ankylosing spondylitis

Article highlights

• Besides the already approved drugs we now have more agents which obviously work in axSpA.

• There is clear evidence that TNFi work but also IL-17 inhibitors (IL-17i), and bimekizumab targeting not also IL-17A but also IL-17F may be even a bit better, but this has not been shown in axSpa, only in psoriasis.

• IL-17i are safe but there may be an issue for bimekizumab with candidiasis. However, side effects are probably mild. More experience and more data are needed.

• Furthermore, JAKi do work in axSpA, and this has been shown for tofacitinib, upadacitinib and filgotinib. At present, only tofacitinib and upadacitinib are approved for AS.

• There are discussions about the safety of JAKi, and there is an FDA black box warning out. Patients with cardiovascular and/or thromboembolic risks should only be treated when there are no alternatives.

• The issue with problems of sperm production related to intake of filgotinib seems to be resolved.

This box summarizes key points contained in the article.

Declaration of interest

J Braun has received honoraria for talks, advisory boards, paid consultancies and grants for studies from Abbvie, Amgen, Biogen, Bristol Myers Squibb, Boehringer, Celltrion, Chugai, Fresenius, GlaxoSmithKline, Galapagos, Hexal, Janssen, Lilly, Medac, Merck Sharp & Dohme, Mylan, Mundipharma, Novartis, Pfizer, Sanofi-Aventis and UCB. U Kiltz has received honoraria for talks, advisory boards, paid consultancies and grants for studies from Abbvie, Amgen, Biogen, Bristol Myers Squibb, Fresenius, GlaxoSmithKline, Galapagos, Hexal, Janssen, Lilly, Merck Sharp & Dohme, Mylan, Novartis, Pfizer and Union Chimique Belge. X Baraliakos has received honoraria for talks, advisory boards, paid consultancies and grants for studies from Abbvie, Amgen, Biogen, Bristol Myers Squibb, Boehringer, Celltrion, Chugai, Fresenius, GlaxoSmithKline, Galapagos, Hexal, Janssen, Lilly, Medac, Merck Sharp & Dohme, Mylan, Mundipharma, Novartis, Pfizer, Sanofi-Aventis and Union Chimique Belge. 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 or other relationships to disclose.

Additional information

Funding

This paper was not funded.