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

• Published in: Multiple sclerosis and related disorders 2024-12, Vol.92, p.106156, Article 106156
• Main Authors: Noll, Giovani, de Lima, Marcos Madeira, Mantovani, Gabriel Paulo, Pineda, Felipe Gutierrez, Silva, Yasmin Picanço, Marcarini, Pedro Guimarães, Reis, Lucas Gabriel Mappes Reimao, Konzen, Viviana Regina, Finkelsztejn, Alessandro
• Format: Article
• Language: English
• Subjects: Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Immunotherapy; Interleukin-6 - antagonists & inhibitors; Interleukin-6 Inhibitors; Meta-analysis; Neuroinflammatory diseases; Neuromyelitis optica; Neuromyelitis Optica - drug therapy
• ISSN: 2211-0348; 2211-0356; 2211-0356
• DOI: 10.1016/j.msard.2024.106156

•Relapse prevention is critical to reduce disability in NMOSD.•Traditionally, long-term treatment involved corticosteroids and azathioprine.•Recent studies provided data indicating the efficacy of IL-6 inhibitors.•IL-6 inhibitors demonstrate higher efficacy without increasing safety concerns. Interleukin-6 (IL-6) inhibitors recently emerged as a promising therapy for neuromyelitis optica spectrum disorder (NMOSD). We performed a systematic review and meta-analysis comparing IL-6 inhibitors to placebo or traditional immunosuppressants in NMOSD. 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. 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; I² = 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; I² = 0 %), adverse events (odds ratio (OR) 1.59; 95 % CI 0.45, 5.63; p = 0.48; I² = 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 %). IL-6 inhibitors demonstrate superior efficacy in preventing relapses in NMOSD compared to placebo or traditional immunosuppressants, without a notable increase in safety risks.