Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients

Abstract

BackgroundRecent years have seen the emergence of disease-modifying therapies in multiple sclerosis (MS), such as anti-cluster of differentiation 20 (anti-CD20) monoclonal antibodies, aiming to modulate the immune response and effectively manage MS. However, the relationship between anti-CD20 treatments and immunoglobulin G (IgG) levels, particularly the development of hypogammaglobulinemia and subsequent infection risks, remains a subject of scientific interest and variability. We aimed to investigate the intricate connection between anti-CD20 MS treatments, changes in IgG levels, and the associated risk of hypogammaglobulinemia and subsequent infections.MethodPubMed, Scopus, Embase, Cochrane, and Web of Science databases have been searched for relevant studies. The “R” software utilized to analyze the occurrence of hypogammaglobulinemia, infections and mean differences in IgG levels pre- and post-treatment. The subgrouping analyses were done based on drug type and treatment duration. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model.ResultsThirty-nine articles fulfilled our inclusion criteria and were included in our review which included a total of 20,501 MS patients. The overall prevalence rate of hypogammaglobulinemia was found to be 11% (95% CI: 0.08 to 0.15). Subgroup analysis based on drug type revealed varying prevalence rates, with rituximab showing the highest at 18%. Subgroup analysis based on drug usage duration revealed that the highest proportion of hypogammaglobulinemia occurred in individuals taking the drugs for 1 year or less (19%). The prevalence of infections in MS patients with a focus on different infection types stratified by the MS drug used revealed that pulmonary infections were the most prevalent (9%) followed by urinary tract infections (6%), gastrointestinal infections (2%), and skin and mucous membrane infections (2%). Additionally, a significant decrease in mean IgG levels after treatment compared to before treatment, with a mean difference of 0.57 (95% CI: 0.22 to 0.93).ConclusionThis study provides a comprehensive analysis of the impact of anti-CD20 drugs on serum IgG levels in MS patients, exploring the prevalence of hypogammaglobulinemia, based on different drug types, treatment durations, and infection patterns. The identified rates and patterns offer a foundation for clinicians to consider in their risk-benefit.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=518239, CRD42024518239.