Comparative safety of interleukin inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis of randomized controlled trials.

Background: The safety of biological agents in the treatment of rheumatoid arthritis (RA) is an important factor affecting patient prognosis and treatment adherence. Among them, interleukin inhibitors are an important category. However, the safety of different types of interleukin inhibitors used to treat RA has not been adequately evaluated. The purpose of this study is to evaluate the safety of interleukin inhibitors for the treatment of RA. Methods: Computer-based searches were conducted in PubMed, the Cochrane Library, Embase, and CNKI to retrieve randomized controlled trials of interleukin inhibitors for the treatment of RA up to March 2026. Literature screening, data extraction, and risk of bias assessment were independently performed by two researchers, and the data were analyzed using Stata 13.1 and the R 4.5.3's gemtc package. The network meta-analysis was performed using a Markov Chain Monte Carlo (MCMC) consistent model. Odds ratios (OR) were used as the measure of effect size. Results: A total of 24 RCTs involving 12,915 patients with RA were included. The use of interleukin inhibitors was associated with the occurrence of adverse events (AE) (OR = 1.15, 95% CI [1.09, 1.21], p < 0.0001), serious adverse events (SAEs) (OR = 1.22, 95% CI [1.08, 1.38], p = 0.001), infections (OR = 1.10, 95% CI [1.02, 1.18], p = 0.007), serious infections (OR = 1.35, 95% CI [1.00, 1.83], p = 0.046), AEs leading to discontinuation (OR = 1.65, 95% CI [1.32, 2.06], p < 0.0001), general disorders and administration site conditions (OR = 1.85, 95% CI [1.49, 2.29], p < 0.0001), gastrointestinal AEs (OR = 1.38, 95% CI [1.04, 1.83], p = 0.002), neurological AEs (OR = 1.32, 95% CI [1.03, 1.68], p = 0.024), skin and subcutaneous tissues AEs (OR = 1.86, 95% CI [1.52, 2.28], p < 0.0001), abnormal laboratory investigations (OR = 1.99, 95% CI [1.59, 2.48], p < 0.0001), and increased ALT in laboratory investigations (OR = 1.88, 95% CI [1.36, 2.60], p < 0.0001). However, interleukin inhibitor use was associated with a decrease in musculoskeletal and connective tissue AEs (OR = 0.77, 95% CI [0.62, 0.95], p = 0.014). It is worth noting that characteristics of the included studies may have affected the results, such as sparse networks, short trial durations, rare-event uncertainty, heterogeneity in background MTX/DMARD use, and lack of long-term safety data. Conclusions: Overall, the AEs caused by different interleukin inhibitors vary. However, in clinical practice, our conclusion should be interpreted cautiously according to individual patient circumstances. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/