Work

Monoclonal antibody efficacy in seropositive vs seronegative NMOSD: systematic review and meta-analysis

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Background and objectives Monoclonal antibodies have transformed the treatment of neuromyelitis optica spectrum disorder (NMOSD), yet their comparative efficacy by aquaporin-4 immunoglobulin G (AQP4-IgG) serostatus remains uncertain. We conducted a systematic review and meta-analysis to compare monoclonal antibody efficacy between AQP4-IgG seropositive and seronegative NMOSD patients. Methods We searched PubMed/MEDLINE, Embase, and Cochrane CENTRAL from inception through January 2025 for studies comparing monoclonal antibody efficacy outcomes (rituximab, eculizumab, satralizumab, inebilizumab, tocilizumab, or ravulizumab) between seropositive and seronegative NMOSD patients. Primary outcomes included annualized relapse rate (ARR) and relapse events. Secondary outcomes included disability progression (Expanded Disability Status Scale [EDSS]) and infectious adverse events. Random-effects meta-analysis was performed. The protocol was registered in PROSPERO (CRD1049290). Results Thirteen studies (4 randomized controlled trials [RCTs], 9 observational) comprising 1284 patients (1010 seropositive; 274 seronegative) were included. Seropositive patients had significantly lower relapse risk (risk ratio [RR] = 0.66; 95% CI: 0.49–0.89; p = 0.007; I 2 = 0%; 9 studies), indicating 34% greater efficacy in preventing relapses. An RCT-only subgroup analysis demonstrated a 59% relative risk reduction favoring seropositive patients (RR = 0.41; 95% CI: 0.25–0.69; p = 0.0008; I 2 = 0%). No significant differences were observed for continuous ARR (standardized mean difference [SMD] = 0.23; p = 0.61; I 2 = 94%), disability progression (SMD = 1.07; p = 0.32; I 2 = 96%), or infectious adverse events (RR = 1.13; p = 0.61; I 2 = 0%). Discussion Monoclonal antibodies demonstrate significantly greater efficacy in preventing relapses in AQP4-IgG seropositive compared with seronegative NMOSD patients. Serostatus should inform treatment selection and expectations. Comparable safety profiles support continued use in seronegative patients, though further research is needed to optimize therapeutic strategies for this population.

Source: Journal of Neuroimmunology

DOI: 10.1016/j.jneuroim.2026.578945