OBJECTIVES

: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that mainly affects the optic nerves and spinal cord. In the absence of clinical trials with head-to-head comparison, an indirect treatment comparison (ITC) was conducted utilizing Bucher method to evaluate the comparative safety and tolerability of inebilizumab and eculizumab.

METHODS

: MEDLINE, Embase, Cochrane and clinicaltrials.gov were searched for last 10 years until July 2020 for relevant placebo-controlled clinical trials with inclusion criterion of adult patients with NMOSD, inebilizumab, eculizumab, and derivable safety and tolerability outcomes. Using placebo as the common comparator, the Bucher method for ITC compared inebilizumab with eculizumab for all outcomes to calculate the risk ratio (RR) with 95% confidence intervals (CI) and p-values.

RESULTS

: Literature review yielded two key placebo-controlled RCTs, pooling 373 patients for the ITC. Bucher ITC demonstrated an indirect superiority of inebilizumab compared to eculizumab for safety with significantly lower risk of adverse events (RR: 0.44; 95% CI: 0.22, 0.89; p=0.023). Furthermore, the ITC showed lower risk of serious adverse events (RR: 0.55; 95% CI: 0.14, 2.18; p=0.399) and mortality (RR: 0.22; 95% CI: 0.00, 35.32; p=0.570) with inebilizumab versus eculizumab, however the comparisons were non-significant. In terms of tolerability, the results were not favourable for inebilizumab compared to eculizumab for discontinuation due to adverse events (RR: 16.46; 95% CI: 0.22, 1235.29; p=0.205) and wider CIs were observed due to smaller number of events within the trials.

CONCLUSIONS

: While comparing treatments for NMOSD indirectly, the Bucher ITC favored inebilizumab for safety and eculizumab for tolerability among adult patients. In the absence of head-to-head comparison, these findings will be useful for health decision makers to make an informed decision for the treatment of NMOSD. Further, high-quality RCTs and systematic reviews are required for conclusive determination of comparative effectiveness, safety and tolerability.