Anti-IL-17 Agents in the Treatment of Axial Spondyloarthritis

Abstract

Axial spondyloarthritis (axSpA) describes a group of chronic inflammatory rheumatic diseases primarily involving the axial skeleton. IL-17 is involved in the pathogenesis of numerous inflammatory diseases, including inflammatory arthritis. Until a few years ago, the only biological agents licensed for the treatment of axSpA and nr-axSpA were TNF inhibitors. However, as some patients did not respond to TNF inhibition or experienced secondary failure, the introduction of the first two IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) has extended the treatment options, and there are now three others (bimekizumab, brodalumab and netakimab) in various stages of clinical development. The last ten years have seen the development of a number of therapeutic recommendations that aimed at improving the management of axSpA patients. The aim of this narrative review of the published literature concerning the role of IL-17 in the pathogenesis of SpA, and the role of IL-17 inhibitors in the treatment of axSpA, is to provide a comprehensive picture of the clinical efficacy and safety of the drugs themselves, and the treatment strategies recommended in the international guidelines.

Residual Disease in Patients with Axial Spondyloarthritis: A Post-Hoc Analysis of the QUASAR Study

“…Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammation and new bone formation in the sacroiliac joints and spine and include non-radiographic axSpA and radiographic axSpA (also known as ankylosing spondylitis (AS)) [ 1 , 2 , 3 ]. Treatment options for axSpA include non-steroidal anti-inflammatory drugs and biologic disease-modifying anti-rheumatic drugs (bDMARDs) that target tumour necrosis factor-alpha (TNFα) or interleukin (IL)-23/17 axes [ 4 , 5 , 6 , 7 , 8 ]. The efficacy of TNFα and IL-23/17 inhibitors in controlling signs and symptoms of axSpA has been shown in clinical trials [ 4 , 5 , 6 ].…”

Efficacy and safety of guselkumab in biologic-naïve patients with active axial psoriatic arthritis: study protocol for STAR, a phase 4, randomized, double-blinded, placebo-controlled trial

“…AxPsA as a unique presentation is supported by differing responses among patients with axSpA to biological agents that target the IL-23/IL-17 axis. Despite the efficacy of IL-12/23 and IL-23 inhibitors in PsA [ 9 , 16 – 18 ] and the efficacy of IL-17 inhibitors in PsA and axSpA [ 37 , 38 ], a trial of an IL-23 inhibitor, risankizumab, in AS demonstrated negative results [ 39 ]. Additionally, cumulative evidence from three phase 3 placebo-controlled trials of patients with axSpA showed that patients treated with the anti-IL-12/23p40 monoclonal antibody ustekinumab did not achieve clinically meaningful improvement across key efficacy endpoints when compared with placebo [ 15 ].…”

Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis

“…Interestingly, in favor of the anti-inflammatory function of irisin, we also disclosed that serum irisin positively correlated with C-peptide, another molecule with similar beneficial effects on inflammation ( 40 ). Of note, a previous study performed in patients with type 2 diabetes mellitus reported an inverse association between irisin and interleukin (IL)-17A ( 41 ), one of the main pro-inflammatory cytokines implicated in the pathogenesis of axSpA ( 1 ). IL-17A was suggested to exert an indirect pro-atherosclerotic role in obese individuals ( 42 ).…”

“…Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton (spine and pelvic joints), although its main symptoms can also be accompanied by extra-articular manifestations ( 1 ). axSpA has detrimental effects on the health status of the patients affected by this condition including, but not limited to, pain, stiffness and poor physical function ( 2 ).…”