ObjectiveWe wanted to evaluate efficacy on inflammatory parameters of rituximab (RTX)-personalized reinfusion scheme using a memory B cell–based treatment regimen.MethodsThis is a prospective, uncontrolled, open-label study including patients with MS treated with RTX in 2 Italian MS units. All patients were treated with RTX induction, followed by maintenance infusion at the dosage of 375 mg/m², according to memory B cell repopulation (0.05% of peripheral-blood mononuclear cells [PBMCs] for the first 2 years, 0.1% of PBMC for the third year). MS activity was assessed as clinical or MRI activity.ResultsOne hundred two patients were included in the analysis. Mean follow-up was 2.40 years (range 0.57–7.15 years). The annualized relapse rate (ARR) was 0.67 in the year before RTX start and decreased to 0.01 in the 3 years after RTX initiation (global ARR). The proportion of patient with MS activity (i.e., relapse or MRI activity) was 63.16% in the year before RTX start and decreased to 8.7% (0–6 months), 1.3% (6–12 months), 0% (12–24 months), and 0% (24–36 months). Annualized RTX infusion rates were 1.67 (95% confidence interval [CI]: 1.43–1.94), 0.76 (95% CI: 0.58–0.98), and 0.78 (95% CI: 0.52–1.12) for the first 3 years after RTX initiation, respectively. Patients were reinfused with a mean infusion interval of 367 days (range 181–839 days).ConclusionThe results of this study show that the memory B cell–based RTX reinfusion protocol is able to reduce the mean number of RTX reinfusions with persistent reduction of disease activity.Classification of evidenceThis study provides Class IV evidence that for patients with MS, a memory B cell–based RTX reinfusion protocol can reduce the mean number of RTX reinfusions with persistent reduction of disease activity.