ObjectiveTo compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin‐4 (AQP4) antibodies.MethodsWe prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B‐cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with <0.05% memory B cells in peripheral blood lymphocytes.ResultsIn 16 patients with MOG antibodies and 29 with AQP4 antibodies, mean follow‐up was 19 (range = 9–38) and 38 (13–79) months. Under RTX, 10 relapses occurred in 6 of 16 (37.5%) patients with MOG antibodies, and 13 occurred in 7 of 29 (24%) with AQP4 antibodies. The median time of relapse after the most recent infusion was 2.6 (0.6–5.8) and 7 (0.8–13) months, respectively (p < 0.001). Memory B cells had reemerged in 2 of 10 (20%) relapses in patients with MOG antibodies and 12 of 13 (92.5%) with AQP4 antibodies (p < 0.001).InterpretationIn AQP4 antibody–associated disorder, relapse mostly occurs when the biological effect of RTX decreases, which argues for treatment efficacy. In MOG antibody–associated disorder, the efficacy of RTX is not constant, because one‐third of patients showed relapse despite an effective biological effect of RTX. In this subpopulation, memory B‐cell depletion was unable to prevent relapse, which was probably caused by different immunological mechanisms. These findings should be used to improve treatment strategies for MOG antibody–associated disorder. ANN NEUROL 2020;87:256–266

Background and ObjectivesTo determine the frequency of hypogammaglobulinemia and infections in patients with multiple sclerosis (PwMS) receiving rituximab (RTX).MethodsThis prospective observational study included all consecutive PwMS receiving RTX at the university hospital of Marseille, France, between 2015 and 2020. Patient visits occurred at least every 6 months.ResultsWe included 188 patients (151 with relapsing-remitting MS; the mean age was 43.4 years [SD 12.9], median disease duration 10 years [range 0–36], median Expanded Disability Status Scale 5 [range 0–8], median follow-up 3.5 years [range 1–5.8], and median number of RTX infusions 5 [range 1–9]). Overall, 317 symptomatic infections and 13 severe infections occurred in 133 of 188 (70.7%) and 11 of 188 (5.9%) patients, respectively. After 4 years, 24.4% of patients (95% CI 18.0–33.1) were free of any infection and 92.0% (95% CI 87.1–97.1) had not experienced a severe infection. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 32 of 188 (17%) patients. After RTX, IgG level was <7, <6, <4 and <2 g/L for 83 (44%), 44 (23.4%), 8 (4.2%) and 1 (0.53%) patients, respectively. The risk of infection was associated with reduced IgG levels (multivariate Cox proportional hazards hazard ratio [HR] = 0.86, 95% CI 0.75–0.98, p = 0.03). The risk of reduced IgG level <6 g/L increased with age (HR = 1.36, 95% CI 1.05–1.75, p = 0.01).DiscussionIn PwMS receiving RTX, reduced IgG level was frequent and interacted with the risk of infection.