Real-World Multicenter Cohort Study of Inebilizumab vs Low-Dose Rituximab in Neuromyelitis Optica Spectrum Disorders.

Abstract

Background and objectives: Inebilizumab and rituximab (RTX) are anti-CD19 and anti-CD20 B cell-depleting antibodies, respectively. They are both used in the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, limited data on both drugs exist regarding real-world clinical applications. This study aimed to assess the efficacy and safety of inebilizumab vs low-dose RTX in NMOSD patients through a retrospective-prospective multicenter analysis.

Methods: This study collected data on aquaporin-4 immunoglobulin G seropositive NMOSD patients from 6 cities in China among those receiving either inebilizumab or low-dose RTX (500 mg), with a 1-year follow-up. Analyses assessed outcomes using inverse probability of treatment weighting and doubly robust models.

Results: We included a total of 229 patients, comprising 119 treated with inebilizumab and 110 with low-dose RTX. The cohort was predominantly female (217/229, 94.76%). The median follow-up duration was 12.0 months (range: 4.0-12.0) in the inebilizumab group and 12.0 months (range: 7.0-12.0) in the low-dose RTX group. Relapses occurred in 8/119 (6.72%) inebilizumab recipients vs 24/110 (21.82%) low-dose RTX recipients (hazard ratio [HR] 3.77, 95% confidence interval [CI] 1.56-9.14; p = 0.003). Adjusted annualized relapse rates were significantly lower in the inebilizumab group (0.06) than in the low-dose RTX group (0.24), corresponding to an incidence rate ratio (IRR) of 3.65 (95% CI 1.59-8.39; p = 0.003). Adverse events (AEs) occurred in 35 patients (29.42%) with inebilizumab, including 2 serious adverse events (SAEs; 1.68%), vs 44 patients (40.00%) with low-dose RTX (4 SAEs [3.64%]). Both AE and SAE rates showed no statistical difference between groups. The rate of patients with at least 1 infection in inebilizumab group was lower than that in the low-dose RTX group (p = 0.003).

Discussion: In this short-term study, inebilizumab demonstrated greater efficacy in reducing relapse risk, along with significantly lower rates of key adverse events, compared with low-dose RTX in patients with NMOSD. These findings support the use of inebilizumab as an effective and well-tolerated therapeutic option in a broader NMOSD population.

Classification of evidence: This short-term study with a 12-month observation period provides Class III evidence that in patients with NMOSD, inebilizumab is more effective than low-dose RTX in reducing relapses.