Comparative Effectiveness and Safety of Inebilizumab Versus Rituximab in AQP4-IgG-Positive NMOSD

Rituximab (anti-CD20, RTX) and inebilizumab (anti-CD19, INE) represent B-cell-depleting therapies used for aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD); however, direct comparative evidence remains limited. This study aimed to evaluate the real-world comparative effectiveness and safety of RTX versus INE.

This was a retrospective, multicenter, observational study.

In this retrospective cohort study, 103 patients with AQP4-IgG+ NMOSD were included, of whom 40 received INE and 63 received RTX. Overlap weighting based on propensity scores was employed to balance baseline covariates, achieving excellent balance (all standardized mean differences < 0.001). The primary outcomes included annualized relapse rate (ARR) and relapse risk, which were analyzed using weighted Poisson regression and Anderson-Gill mode.

After weighting, the proportion of patients experiencing any relapse was lower in the INE group than in the RTX group (10.6% vs. 43.9%, p = 0.047). In models accounting for differences in follow-up duration, INE was also associated with a lower post-treatment relapse risk than RTX. Although the restricted mean survival time difference at 27 months favored INE, the difference was not statistically significant. Disability progression was similar between groups, though hypogammaglobulinemia, particularly reduced IgG levels, was more frequently observed with INE (54.1% vs. 17.2%; p < 0.001).

In this real-world cohort, INE showed a trend toward lower relapse risk compared to RTX, whereas demonstrating a manageable safety profile with increased incidence of hypogammaglobulinemia.