NMOSD is an inflammatory, immune-mediated astrocytic disease of the central nervous system characterized by monophasic or recurrent optic neuritis, longitudinally extensive transverse myelitis(Carnero Contentti and Correale, 2021; Silbermann and Bourdette, 2019). Although the prevalence of NMOSD is around 12 per 100,000 people, severe immune-mediated attacks can rapidly lead to blindness and paralysis if not diagnosed and treated in time(Silbermann and Bourdette, 2019). The median age at onset is 40 years in European patients and may be lower in Asian and Black patients positive for AQP4-IgG. NMOSD is more common in women, especially among AQP4-IgG-positive patients (male to female ratio 1:9 ∼ 1:10) (Jarius et al., 2020). The majority of patients with NMOSD experienced severe relapses resulting in permanent neurological deficits, making curbing the frequency and severity of relapses a major goal of disease management. Due to its high relapse rate and disability, it seriously affects people's quality of life and imposes a serious burden on families, countries, and society.

The current standard of care for NMOSD acute relapse is early intravenous methylprednisolone with intravenous immunoglobulin(IVIG) or plasma exchange. AQP4-IgG seropositivity is associated with a high risk of recurrence in patients with a first episode of longitudinally extensive transverse myelitis and single or recurrent optic neuritis. AQP4-IgG is a strong predictor of future recurrence, and early preventive treatment can help avoid severe disability in patients with NMOSD. Regular immunosuppressive therapies have been used to prevent relapses and these include rituximab, mycophenolate mofetil(MMF), azathioprine(AZA), and prednisone(Levy et al., 2021). A meta-analysis published in 2021, showed that rituximab was more effective in NMOSD than MMF or AZA in preventing attacks(Giovannelli et al., 2021). Rituximab is a monoclonal antibody against the CD20 molecule, which produces depletion of B lymphocytes due to complement cytotoxicity and phagocytosis by macrophages (Gomez-Figueroa et al., 2020). Studies have shown that rituximab is more effective than AZA and MMF in reducing ARR and severity of relapse and in preventing new relapses(Jeong et al., 2016; Mealy et al., 2014; Stellmann et al., 2017). A phase 2/3 multicentre double-blind randomized controlled trials(RCT) (RIN-1) study evaluating rituximab in patients with NMOSD was conducted in Japan and showed that after 72 weeks of follow-up, patients treated with rituximab had a significantly lower ARR than placebo (0% vs 0.37%) with no statistically significant difference in EDSS (Tahara et al., 2020).

The efficacy, safety, tolerability, and practical considerations (including potential cost) of each drug vary, which may affect the use of patients with NMOSD in real-world populations(Levy et al., 2021). Previous studies and clinical trials have demonstrated the effectiveness of rituximab, however, the optimal dose regimen remains a key issue and there is still considerable controversy regarding its dose. Therefore, we focused on a meta-analysis of different dose regimens for rituximab treatment in NMOSD. In previous clinical trials, rituximab has demonstrated flexible dose regimens [a.100mg IV, one infusion per week for 3 consecutive weeks; b.375mg/m2 (body surface area) once; c.average 500mg per dose and 2g totally in 4 weeks; d.375 mg/m2 weekly for 4 weeks; e.two doses of 1000mg each, at an interval of 2 weeks.] In our study, we combined different doses of rituximab to analyze the efficacy and safety of the treatment in NMOSD.