Efficacy and Safety of IL-17 and JAK Inhibitors in Ankylosing Spondylitis: A Systematic Review and Network Meta-Analysis

Objective: The aim of this study was to compare the clinical efficacy and safety of interleukin-17 inhibitors and Janus kinase inhibitors in the treatment of ankylosing spondylitis based on a network meta-analysis. Methods: According to the search strategy, systematic retrievals were conducted in PubMed, Embase, Web of Science, the Cochrane Register of Clinical Trials, Scopus, and website ClinicalTrials.gov, from the establishment to December 8, 2023. Randomized controlled trials (RCTs) of interleukin-17 inhibitors and Janus kinase inhibitors for the treatment of ankylosing spondylitis were selected according to the inclusion and exclusion criteria. The included studies were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Software Stata 16.0, to compare the effectiveness and safety differences in all interventions. Results: A total of 18 RCTs involving 3968 subjects were included in this study. The interventions were ranked from best to worst in terms of ASAS20: netakimab 120 mg > filgotinib 200 mg > tofacitinib 5 mg> brodalumab 210 mg >upadacitinib 15 mg >bimekizumab 160 mg > secukinumab 300 mg> ixekizumab 80 mg Q4W > secukinumab 150 mg > secukinumab 150 mg no LD> placebo, netakimab 120 mg outperformed all other interventions and the difference was statistically significant. The interventions were ranked from best to worst in terms of ASAS40: netakimab 120 mg > tofacitinib 5 mg > secukinumab 150 mg > secukinumab 300 mg > upadacitinib 15 mg > bimekizumab 160 mg> ixekizumab 80 mg Q4W > filgotinib 200 mg > brodalumab 210 mg > secukinumab 150 mg no LD > placebo, netakimab 120 mg outperformed all other interventions and was statistically significant (except the intervention of filgotinib 200 mg). In terms of AEs and SAEs, there was no statistical significance among all interventions. Conclusions: The results of the network meta-analysis showed that netakimab 120mg ranked relatively high in outcome of ASAS20 and ASAS40. All treatments with IL-17 and JAK inhibitors were generally safe and well tolerated. However, the two included netakimab clinical studies may have limitations. Therefore, the therapeutic agents should be carefully selected in clinical treatment. Moreover, the efficacy and safety of netakimab remain to be further analyzed in studies with larger sample sizes and longer follow-up times.