OBJECTIVES : Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is a chronic disorder of the brain and spinal cord dominated by inflammation of the optic nerve (optic neuritis) and inflammation of the spinal cord (myelitis). Patients with NMOSD had eculizumab as the only FDA-approved treatment until 2019. This study attempts to synthesize a network meta-analysis (NMA) and assess comparative safety and tolerability of eculizumab with recently approved inebilizumab for adult NMOSD patients.

METHODS : A targeted literature review was conducted for last 10 years until July 2020 using Ovid platform for English language publications in MEDLINE, Embase, and Cochrane Library on eculizumab and inebilizumab for adult patients. Study quality of included records was assessed using the Cochrane Risk of Bias instruments. Network meta-analysis (NMA) was conducted using R v4.0.0 and OpenBUGS v3.2.3 to calculate the risk ratio (RR) with 95% credible intervals (CrIs) for all outcomes.

RESULTS : Literature review identified two key placebo-controlled RCTs, pooling 373 patients for the NMA. Fixed effects model results showed inebilizumab to be the safest treatment in NMOSD patients compared to eculizumab with lower risks of adverse event (RR: 0.99; 95% CrI: 0.81, 1.31) serious adverse event (RR: 0.58; 95% CrI: 0.16, 2.13) and mortality (RR: 0.11; 95% CrI: 0.00, 145.50). However, eculizumab was more tolerable with lower risk of discontinuation due to adverse events compared to inebilizumab (RR: 0.01; 95% CrI: 0.00, 1.21). The results were comparable with no significant differences among the comparisons. The sparseness of the evidence networks entails high uncertainty and associated wide credible intervals.

CONCLUSIONS : This NMA presents the first comparative safety and tolerability results of treatments approved for NMOSD. Both inebilizumab and eculizumab have comparatively similar safety and tolerability profile in adult patients. Wide heterogeneity in evidence warrants more robust trial designs investigating long-term treatments for this disease.