Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 monoclonal antibodies: a systematic review and meta-analysis of observational studies

Introduction: Monoclonal antibodies (mAbs) targeting CD20 used in patients with multiple sclerosis (MS) can cause hypogammaglobulinemia, increasing the risk of infections. We aim to identify the proportion of individuals developing these events during the treatment with an anti-CD20 mAb. Methods: A systematic review of observational studies was conducted from 2014 to 2024. Studies involving patients with MS, receiving anti-CD20 mAbs, evaluating outcomes related to hypogammaglobulinemia and/or infections were included. A random effect meta-analysis approach was used. Results: 55 articles were selected for meta-analysis, covering a population of 14,548 MS patients. Overall, rituximab exhibited a higher prevalence of hypogammaglobulinemia [11%; 95% Confidence Interval (CI): 0.08 to 0.15], infections of any grade (25%; 95%CI: 0.18 to 0.32), genito-urinary infections (9%;95%CI: 0.05 to 0.12), while ocrelizumab exhibited a higher prevalence of serious infections (6%; 95%CI: 0.03 to 0.09) and respiratory infections (12%; 95%CI: 0.07 to 0.17). The paucity of data for ofatumumab and ublituximab highlights a research gap. The proportion of these AEs increase with treatment duration. Substantial heterogeneity was identified in all analyses. The quality of included studies was mainly classified as poor. Conclusions: Monitoring and educating patients on anti-CD20 mAb is fundamental to quickly identifying adverse events and minimizing clinical risks. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42024617575.