Interleukin-6 inhibitors for neuromyelitis optica spectrum disorder (NMOSD): A systematic review and meta-analysis

Background: Interleukin-6 (IL-6) inhibitors recently emerged as a promising therapy for neuromyelitis optica spectrum disorder (NMOSD). Objective: We performed a systematic review and meta-analysis comparing IL-6 inhibitors to placebo or traditional immunosuppressants in NMOSD. Methods: We searched PubMed, Embase, and Cochrane Central for eligible studies. Efficacy endpoints included hazard ratio (HR) for relapse, annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) change over time. Safety outcomes comprised any adverse event, serious adverse events and infections. Statistical analysis was performed using RevMan Web and R studio package meta. Heterogeneity was assessed with I2 statistics. Results: Four studies involving 361 patients (228 treated with IL-6 inhibitors) were included. IL-6 inhibitors significantly reduced HR for relapse (HR 0.35; 95 % CI 0.23, 0.55); p < 0.00001; I-2 = 0 %) and ARR (mean difference -0.79 relapses/year; 95 % CI -1.54, -0.03; p = 0.04; I2 = 96 %) compared to placebo or traditional immunosuppressants. No significant differences were observed in EDSS change over 24 weeks of follow-up (mean difference -0.18; 95 % CI -0.41, 0.05; p = 0.93; I-2 = 0 %), adverse events (odds ratio (OR) 1.59; 95 % CI 0.45, 5.63; p = 0.48; I-2 = 48 %), serious adverse events (OR 0.76; 95 % CI 0.40, 1.44; p = 0.50; I2 = 0 %) and infection rates (OR 1.10; 95 % CI 0.67, 1.79; p = 0.71; I2 = 0 %). Conclusion: IL-6 inhibitors demonstrate superior efficacy in preventing relapses in NMOSD compared to placebo or traditional immunosuppressants, without a notable increase in safety risks.