Comprehensive Review of Hypogammaglobulinemia and Infection Rates in MS Patients Treated with Anti-CD20 Antibodies
Anas Elgenidy1, Omar Alomari2, Mohammed Al-mahdi Al-kurdi3, Lobna A. Mohamed4, Mohamed M. Ghoneim5, Ahmed Wagdy Fathy6, Hazem Khaled Hassaan7, Ahmed Anan8, Nagham Nader Abdelhalim9
1Department of Neurology, Kasr Al-Aini, Cairo University, Egypt, 2Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Turkey, 3Faculty of Medicine, University of Aleppo, Aleppo, Syrian Arab Republic, 4Faculty of Medicine, Alexandria University, Egypt, 5Faculty of Medicine, Menoufia University, Egypt, 6Faculty of Medicine, Kafrelshikh University, Egypt, 7Faculty of Medicine, Benha University, Egypt, 8Faculty of Medicine Suez Canal University, Egypt, 9Faculty of Medicine, Cairo University, Egypt
Objective:
To investigate the relationship between anti-CD20 treatments in Multiple Sclerosis (MS), serum immunoglobulin G (IgG) levels, and the risk of hypogammaglobulinemia and infections, aiming to inform treatment strategies to prevent severe infections.
Background:
MS is an autoimmune disorder characterized by demyelination in the central nervous system, affecting young adults and leading to significant neurological disability. The disease presents as either relapsing or progressive, with varying clinical manifestations. Disease-modifying therapies, including anti-CD20 monoclonal antibodies (e.g., rituximab), have revolutionized MS management by targeting B-cells. However, these treatments may cause hypogammaglobulinemia, increasing infection risks. There is a need for standardized data to guide treatment adjustments based on IgG levels.
Design/Methods:
This systematic review followed the PRISMA and searched major databases up to late 2024, using a comprehensive strategy. Studies included examined the effects of anti-CD20 treatments on IgG levels in MS patients. Meta-analysis was conducted using R software, with heterogeneity assessed using I² and chi-squared tests.
Results:
From 39 studies, encompassing 20,501 MS patients across various countries, we found an 11% prevalence of hypogammaglobulinemia (95% CI:0.08-0.15; I² >91%). Subgroup analysis based on drug type revealed varying prevalence rates, with rituximab showing the highest at 18%. Subgroup analysis showed the highest rate of hypogammaglobulinemia (19%) in those using the drugs for one year or less. Among MS patients, pulmonary infections were most common (9%), followed by urinary tract infections (6%), gastrointestinal infections (2%), and skin/mucous membrane infections (2%), varying by the MS drug used. Additionally, mean IgG levels significantly decreased after treatment, with a mean difference of 0.57 (95% CI:0.22-0.93).
Conclusions:
Anti-CD20 therapies in MS are associated with varying risks of hypogammaglobulinemia and infections. Rituximab exhibits the highest risk, necessitating close monitoring of IgG levels and infection management. Standardized guidelines are essential for optimizing treatment strategies and improving patient outcomes.
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