Secondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management
- PMID: 37783194
- DOI: 10.1016/j.msard.2023.105009
Secondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management
Abstract
Hypogammaglobulinemia is characterized by reduced serum immunoglobulin levels. Secondary hypogammaglobulinemia is of considerable interest to the practicing physician because it is a potential complication of some medications and may predispose patients to serious infections. Patients with multiple sclerosis (MS) treated with B-cell-depleting anti-CD20 therapies are particularly at risk of developing hypogammaglobulinemia. Among these patients, hypogammaglobulinemia has been associated with an increased risk of infections. The mechanism by which hypogammaglobulinemia arises with anti-CD20 therapies (ocrelizumab, ofatumumab, ublituximab, rituximab) remains unclear and does not appear to be simply due to the reduction in circulating B-cell levels. Further, despite the association between anti-CD20 therapies, hypogammaglobulinemia, and infections, there is currently no generally accepted monitoring and treatment approach among clinicians treating patients with MS. Here, we review the literature and discuss possible mechanisms of secondary hypogammaglobulinemia in patients with MS, hypogammaglobulinemia results in MS anti-CD20 therapy clinical trials, the risk of infection for patients with hypogammaglobulinemia, and possible strategies for disease management. We also include a suggested best-practice approach to specifically address secondary hypogammaglobulinemia in patients with MS treated with anti-CD20 therapies.
Keywords: Anti-CD20; Hypogammaglobulinemia; Multiple sclerosis; Ocrelizumab; Ofatumumab; Ublituximab.
Copyright © 2023. Published by Elsevier B.V.
Conflict of interest statement
Declaration of Competing Interest Enrique Alvarez has received compensation for activities such as advisory boards, lectures, and consultancy from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono/Merck, Genentech/Roche, Novartis, Sanofi, and TG Therapeutics; and has received research support from Biogen, Genentech/Roche, National Institutes of Health, National Multiple Sclerosis Society, Novartis, Patient-Centered Outcomes Research Initiative, Rocky Mountain MS Center, and TG Therapeutics. Erin E. Longbrake has received honoraria for consulting from Bristol Myers Squibb, Genentech, NGM Biopharmaceuticals, and TG Therapeutics; and has received research support from Genentech, National Institutes of Health (K23107624, KL2 TR001862), and Patterson Leet Trust. Kottil Rammohan has received speaking, consulting, and advisory fees from Alexion, Biogen, EMD Serono, Genentech, Genzyme, Horizon Therapeutics, Novartis, and TG Therapeutics; and has served as Principal Investigator or Co-investigator for grants to his institutions from Alexion, Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and TG Therapeutics. James Stankiewicz is an employee and stockholder of Novartis Pharmaceuticals Corporation. Carrie M. Hersh has received speaking, consulting, and advisory board fees from Biogen, Bristol Myers Squibb, DynaMed, EMD Serono, Genentech, Genzyme, Novartis, TG Therapeutics, and Alexion; and has received research support paid directly to her institution by Biogen, Genentech, National Institutes of Health-National Institute of Neurological Disorders and Stroke (1U01NS111678–01A1 sub-award), Novartis, and Patient-Centered Outcomes Research Institute.
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