B-lymphocyte-guided retreatment contributes to establish good effectiveness and safety profile in MS patients treated with rituximab

•Rituximab is an effective treatment for multiple sclerosis patients.•During follow-up, a substantial increase of BL counts was preceded by initial values of 0.2–0.3%.•Rituximab retreatment guided by this cut-off BL showed high effectiveness in MS patients.•This approach may reduce adverse such as infections or hypogammaglobulinemia, thus allowing long-term therapy. Rituximab is extensively used for multiple sclerosis (MS) treatment. However, the best dosage remains to be established. It has been proposed that retreatment could be guided by B lymphocyte (BL) percentages. To establish the best BL value for retreatment with rituximab in MS and to confirm the safety and efficacy of this approach. A prospective study was done with an exploratory cohort and a confirmatory cohort of MS patients treated with rituximab between 2017 and 2021. The first one comprised 10 MS patients with BL assessed every 3 months after rituximab infusion and retreatment done when BL values were ≥0.5%. The confirmatory cohort included 41 MS patients (41.5% women, 87.8% with secondary progressive MS, median age = 46.3 (interquartile range: 41.3–52.1) years, disease duration = 14.1 (9–19.6) years, EDSS score = 5.5 (4.0–6.5)). The confirmatory cohort was treated with rituximab following the pattern established in the exploratory cohort. In the exploratory cohort, ≥0.2% BL was established as the best value for retreatment because in most cases, a substantial increase of BL counts was preceded by initial values of 0.2–0.3%. In the confirmatory cohort, rituximab reduced the annualized relapse rate (ARR 0.56 vs. 0.125, p