Long-term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder and MOG Antibody Disease

Background and Objectives: Rituximab is used widely for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-IgG associated disease (MOGAD), however data regarding the effectiveness and safety of long-term rituximab use in these conditions are limited. In this study we sought to evaluate long-term clinical outcomes in patients with aquaporin-4 IgG seropositive (AQP4-IgG+) NMOSD and MOGAD treated with rituximab.

Methods: We performed a retrospective chart review of patients with AQP4-IgG+ NMOSD or MOGAD followed at the Johns Hopkins Neuromyelitis Optica Clinic and included patients who had received at least one dose of rituximab.

Results: We identified 111 NMOSD and 23 MOGAD patients who fulfilled inclusion criteria. Median duration of rituximab treatment for the NMOSD patients was 3.7 years (range:0.5 to 13.2) and for the MOGAD patients was 2.1 years (range:0.5 to 7.0). The annualized relapse rate (ARR) decreased after rituximab initiation in both NMOSD (median ARR:pre-treatment 1.1, post-treatment 0; p<0.001) and MOGAD (median ARR:pre-treatment 1.9, post-treatment 0.3; p=0.002). Relapses on rituximab occurred in 31 NMOSD (28%) and 14 MOGAD (61%) patients. The majority of NMOSD treatment failures (37/48 relapses; 77%) occurred either within the initial 6-months after starting rituximab (n=13 relapses) or in the setting of delayed/missed rituximab doses and/or peripheral B cell reconstitution (n=24 relapses) whereas in MOGAD, these circumstances were present in a smaller proportion of treatment failures (19/35 relapses; 54%). The risk of relapse on rituximab was greater for MOGAD compared to NMOSD patients (hazard ratio:2.8, 95%CI: 1.5 to 5.2, p=0.001). Infections requiring hospitalization occurred in 13% and IgG hypogammaglobulinemia in 17% of patients. Median rituximab treatment duration before IgG hypogammaglobulinemia onset was 5.4 years (IQR:3.8 to 7.7).

Conclusions: Rituximab treatment is associated with reduced annualized relapse rate in AQP4-IgG seropositive NMOSD, especially in the absence of gaps in treatment and/or B cell reconstitution. In MOGAD, while a reduction in relapses was observed after initiation of rituximab, this association appeared to be less robust than in AQP4-IgG seropositive NMOSD. Severe infections and hypogammaglobulinemia occurred in a significant proportion of patients, highlighting the need for close monitoring of infectious complications.

Classification of Evidence: This study provides Class IV evidence that rituximab decreases the annualized relapse rate in AQP4-IgG seropositive NMOSD and MOGAD.