Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

Yufeng Yin,Xin Chang,Tian Ren,Keqin Zeng,Mingjun Wang,Erye Zhou,Michun He,Yufan Guo,Mengru Liu,Jian Wu

doi:10.1186/s13075-020-02208-w

Abstract

ObjectivesTo systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis.MethodsA systematic review of the literature was performed for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. Meta-analyses were used to determine the efficacy and safety of the IL-17 inhibitors in the treatment of these patients. The primary endpoint was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary endpoint was defined as ASAS40 at week 16.ResultsSix phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR = 1.63, 95% CI 1.45 to 1.84, p = 0.00) and the secondary endpoint ASAS40 response rate (RR = 2.12, 95% CI 1.75 to 2.56, p = 0.00) versus those for the placebo. With respect to the safety profile, more treatment-emergent adverse events (RR = 1.11, 95% CI 1.01 to 1.22, p = 0.03) and non-severe infections (RR = 1.82, 95% CI 1.40 to 2.37, p < 0.001) were described after treatment with IL-17 inhibitors than after treatment with placebo, while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including death, discontinuation due to adverse events, or serious adverse events.ConclusionsIL-17 inhibitors produced favorable response rates but an increased risk of non-severe infections in the treatment of active ankylosing spondylitis.

Highlights

Ankylosing spondylitis is a chronic disease, with a prevalence ranging from 9 to 30 per 10,000 persons of the adult population worldwide [1, 2]
A combination of the following keywords was used: “axial spondyloarthritis,” “ankylosing spondylitis,” “anti-interleukin-17,” “anti-IL-17,” “IL17 receptor blockade,” “anti-IL17R,” “secukinumab,” “ixekizumab,” “brodalumab,” “bimekizumab,” and “netakimab.” The search was independently performed by two investigators (YY and ML), and discrepancies in the study selection were resolved by consensus
Secukinumab was evaluated in 4 trials of 3 published articles [25,26,27], and ixekizumab was used in two articles in the treatment of ankylosing spondylitis [28, 29]

Summary

Introduction

Ankylosing spondylitis is a chronic disease, with a prevalence ranging from 9 to 30 per 10,000 persons of the adult population worldwide [1, 2]. Ankylosing spondylitis is generally characterized by irreversible and structural damage of the sacroiliac and spinal joints, and progressive spinal ankylosis due to new bone formation [3]. Clinical presentations of these patients include chronic back pain, morning stiffness, and loss of spinal mobility, which primarily affect the pelvis and the lower back [3]. For patients who do not respond to or tolerate NSAIDs, biological disease-modifying antirheumatic drugs (bDMARDs), mainly tumor necrosis factor inhibitors (TNFis), have been recommended since the early 2000s [4, 5]. The emergence of interleukin (IL)-17 inhibitors has changed the treatment landscape of active ankylosing spondylitis [10]

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