Role of C5 inhibitors in Neuromyelitis Optica Spectrum Disorders with Seropositive Anti-aquaporing-4 Antibody: A Systematic Review and Meta-Analysis

Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve and the spinal cord. C5 complement inhibition is an effective therapeutic approach in the treatment of NMOSD. In this systematic review and meta-analysis, we aimed to determine the role of C5 inhibitors in the treatment of patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG) NMOSD Methods This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Relevant articles were systematically searched through Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases until October 6th, 2023. We included randomized clinical trials (RCTs) that investigated the treatment with C5 inhibitors compared to placebo in patients with seropositive NMOSD. The primary endpoint was the rates of first adjudicated relapse. Secondary endpoints included different disability and quality of life measures. The random-effects model was used for all statistical analyses. Results Two RCTs with a total of 201 patients were included. C5 inhibitors demonstrated significant reduction of first adjudicated relapse (risk ratio (RR) = 0.05, 95% CI 0.01-0.15) and Hauser Ambulation Index (HAI) (mean difference (MD): -0.79, 95% CI -1.27 to -0.31). There was no significant difference between the two groups in Expanded Disability Status Scale (EDSS) (MD -0.23, 95% CI -0.54-0.08). C5 inhibitors significantly improved the mean change in EQ-5D index (MD 0.08, 95% CI 0.01-0.14; P = 0.02); however, no significant difference was shown in the mean change in EQ-5D VAS (MD 3.79, 95% CI -1.61 to 9.19; P = 0.17). Safety measures were comparable between C5 inhibitors and placebo. Conclusion NMOSD Patients with AQP4+IgG receiving C5 inhibitors have lower rate of relapses and improved levels of disability and quality of life. Real-world studies are warranted to establish the long-term safety of C5 inhibitors.