Therapeutic response to rituximab in seropositive neuromyelitis optica: Experience from a tertiary care center in South India

Objectives: Neuromyelitis optica (NMO) is a severe central nervous system demyelinating disease caused by autoantibodies to anti-aquaporin-4 immunoglobulin-G (AQP4-IgG). Rituximab, a monoclonal antibody targeting CD20 cells, is effective in neuromyelitis optica spectrum disorder (NMOSD) in several observational studies and small randomized controlled trials. However, this includes both AQP4-IgG antibody positive and negative cases. Whether rituximab is more effective in seropositive NMO is unknown. The aim of the study was to determine the efficacy of rituximab in seropositive NMO. Materials and Methods: This single-center ambispective study with retrospective data collection and prospective follow-up included patients with NMOSD who were positive for AQP4-Ig-G and treated with rituximab. Efficacy outcomes assessed were annualized relapse rate (ARR), disability progression by expanded disability status scale (EDSS), very good outcome (defined as no relapse and an EDSS ≤3.5), and persistent antibody positivity. Safety was also monitored. Results: Between June 2017 and December 2019, 15 AQP4-IgG-positive cases were identified. The mean (± SD) age was 36 ± 17.9 years and 73.3% were females. Transverse myelitis followed by optic neuritis was the most common presentations. Rituximab was initiated after a median period of 19-weeks from the disease onset. The mean number of rituximab doses received was 6.4 ± 2.3. After a mean follow-up duration of 107 ± 74.7 weeks from the first dose of rituximab, ARR significantly reduced from 0.5 ± 0.9 to 0.02 ± 0.08, difference 0.48 ± 0.86 (95% confidence intervals [CI], 0.0009–0.96;P= 0.05). The number of relapses also reduced significantly from 0.6 ± 0.8–0.07 ± 0.26 , a difference of 0.53 ± 0.91 (95% CI, 0.026–1.05;P= 0.041). EDSS also significantly reduced from 5.6 ± 2.5–3.3 ± 2.9 , a difference of 2.23 ± 2.36 (95% CI, 0.93–3.54;P= 0.003). Very good outcome was obtained in 73.3% (11 of 15);P= 0.002. AQP4-IgG remained positive in 66.7% (4 of 6) when repeated after a mean period of 149.5 ± 51.1 weeks after the first dose of rituximab. Neither pre-treatment ARR, EDSS, time to initiate rituximab, the total number of rituximab doses, or time to repeat AQP4-IgG were significantly associated with persistent antibody positivity. No serious adverse events were observed. Conclusion: Rituximab exhibited high efficacy and good safety in seropositive NMO. Larger trials in this subgroup are warranted to confirm these findings.