To evaluate the efficacy and safety of interleukin-6 (IL-6) inhibitors for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD).

 IL-6 inhibitors, including Tocilizumab and Satralizumab, have been studied for relapse prevention in NMOSD, but comparative synthesis is limited.

PubMed, EMBASE, SCOPUS, and Web of Science were searched through September 2025. Two reviewers screened records, extracted data, and assessed quality. A frequentist network meta-analysis was conducted in R (netmeta) using a random-effects model. Comparisons included active agents versus placebo or standard therapy. Outcomes were relapse risk (HR), annualized relapse rate (MD), relapse at 96 weeks (OR), and serious adverse events. Language refinement was assisted by ChatGPT (OpenAI, GPT-5).

Four studies (three RCTs and one cohort study; n = 361) were analyzed. Tocilizumab (8 mg/kg weekly) showed the strongest protection against relapse versus control (HR 0.40, 95% CI 0.26–0.59; OR 0.26, 95% CI 0.15–0.45; both p < 0.0001) and markedly reduced annualized relapse rate (MD –2.26, 95% CI –3.40 to –1.12, p = 0.0001). Satralizumab (120 mg q4w) also significantly reduced relapse versus control (HR 0.55, 95% CI 0.36–0.83, p = 0.0046; OR 0.38, 95% CI 0.20–0.73, p = 0.0038) with a modest effect on relapse rate (MD –0.22, 95% CI –0.36 to –0.09, p = 0.0013). At 96 weeks, Tocilizumab (OR 4.17, 95% CI 2.39–7.27, p < 0.0001) and Satralizumab (OR 2.46, 95% CI 1.28–4.72, p = 0.0066) maintained significant efficacy versus control. No agent increased serious adverse events. Heterogeneity and inconsistency were negligible.

Tocilizumab and Satralizumab significantly reduce relapse risk and maintain efficacy at 96 weeks versus control, without increasing serious adverse events. Further large-scale trials are needed to compare IL-6 inhibitors directly, assess long-term safety, and optimize dosing strategies for NMOSD patients.