Optimal Biologic Drugs for the Treatment of Ankylosing Spondylitis: Results from a Network Meta-Analysis and Network Metaregression

Abstract

Background. Ankylosing spondylitis (AS) is a common immune-related systemic chronic inflammatory osteoarthropathy. Previous studies have proven that biologic agents, including IL-17A inhibitors (IL17Ai), TNF-α inhibitor FC fusion protein (TNFiFCP), or fully human monoclonal antibody (TNFiNMA) and JAK inhibitor (JAKi), are effective for AS treatment. Our study is aimed at comparing the clinical efficacy, tolerability, and safety of different biological agents, including novel IL-6 inhibitor (IL6i), IL-23 inhibitor (IL23i), and IL-17 A/F dual variable domain inhibitor (IL17AFi) in AS. Method. PubMed, Scopus, Embase, CNKI, and the Cochrane Library were systematically searched. A frequentist framework network meta-analysis with a random-effects model was performed. Ranking effects were calculated by surface under the cumulative ranking analysis (SUCRA) and cluster-rank analysis. Results. IL17AFi reported both the highest ASAS40 ( $\text{SUCRA}=91.4$ %) and ASAS20 ( $\text{SUCRA}=92.5$ %) response, while IL6i and IL23i reported the lowest responses ( $\text{SUCRA}=6.6$ % and 19.9%, respectively). With the exceptions of IL6i (RR 0.60, 95% CI (0.22 to 1.67) for ASAS40 and 1.36 (0.71 to 2.58) for ASAS20) and IL23i (0.98 (0.68 to 1.40) for ASAS40 and 0.91 (0.70 to 1.19) for ASAS20), all biological drugs demonstrated statistically superior ASAS responses than placebo. TNFiFMA performed best in the suppression of disease activity ( $\text{SUCRA}=77.4$ %, SMD 2.35, and 95% CI (1.11 to 3.59)) and functional improvement ( $\text{SUCRA}=68.8$ %, SMD 1.67, and 95% CI (0.59 to 2.74)). There were no significant differences in tolerability or safety between biologic drugs and placebo. Conclusions. The novel IL-17 A/F dual variable domain inhibitor, bimekizumab, may be an ideal future treatment choice for AS, while IL-23 and IL-6 inhibitors demonstrate little potential in the treatment of AS. For patients with rapid disease progression and severe functional limitation, TNF-α inhibitors, especially infliximab, are safe and effective and could be a first-line treatment choice.