Immune-related adverse events (irAEs) in ankylosing spondylitis (AS) patients treated with interleukin (IL)-17 inhibitors: a systematic review and meta-analysis

摘要

Background Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by immune system dysregulation and inflammation in the joints. Interleukin (IL)-17 inhibitors are new biological drugs used to treat AS. In this study, we aimed to assess the risk of immune system-related AEs due to targeting IL-17 or IL-17R. Methods The CENTRAL, PubMed, Scopus, Google Scholar, Clinical Trials Registry, and ICTRP were searched for randomized clinical trials (RCTs) and non-RCTs until February 2021. The risk of irAEs in patients treated with IL-17 inhibitors compared to the placebo or a drug-free control was evaluated. In studies that reported AEs of the IL-17 inhibitors at several different time points, we compared the number of cases/100 patient-year in which irAEs were reported. Subgroup analyses were also performed based on the dose and type of drugs. Results Thirteen studies of 1848 AS patients treated by IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, and netakimab) and 764 participants who received a placebo were included. The risk of some AEs related to immune function in patients under IL-17 inhibitors treatment was significantly higher than that of the placebo group, including infection and infestation (risk difference RD = 0.09, P = 0.02), nasopharyngitis (RD = 0.04, P < 0.001), opportunistic infections (RD = 0.01, P = 0.04), and neutropenia (RD = 0.04, P = 0.03). Besides, the results of the Cochran Q test showed that there were significant differences between the occurrence of some AEs over time, including infection and infestations (p < 0.001, RCTs), upper respiratory tract infections (p < 0.001, non-RCTs), urinary tract infections (p < 0.001, non-RCTs), and diarrhea (p < 0.01, RCTs). Conclusions The most common immune system-related AEs in patients treated with IL-17 inhibitors are mucosal and opportunistic infections.