Hypogammaglobulinemia and Infection Risks in Multiple Sclerosis Patients Receiving Anti-Cd20 Monoclonal Antibodies: Incidence, Clinical Implications, and Longitudinal Insights From a Three-Year Iranian Cohort Publisher Pubmed



Fallah EA ; Emami A ; Moghaddam NB ; Ghaffari M ; Meshkini F ; Paybast S
Source: Multiple Sclerosis and Related Disorders Published:2026

Abstract

Introduction: Anti-CD20 monoclonal antibodies are regarded as high efficacy disease-modifying therapy (DMT) for management of multiple sclerosis (MS). However, prolonged B-cell depletion might increase the risk of secondary hypogammaglobulinemia (SHG) and serious infections. Herein, we aimed to investigate the incidence, severity, and clinical correlates of SHG in MS patients receiving rituximab and ocrelizumab. Methods and materials: Between January 2018 and February 2023, MS patients prescribed rituximab and ocrelizumab at Imam Hossein MS Center in Tehran, Iran, were identified. Clinician-reported data were retrospectively collected. Results: 254 patients were enrolled. The majority (73.2 %) were female with a mean age of 41.22 ± 9.79 and a mean disease duration of 9.79 ± 5.46 years. Mean IgG levels declined from 1108.6 ± 205.6 mg/dL at baseline to 880.7 ± 199.9 mg/dL after three years. Over a mean follow-up of 44.43 ± 15.95 months, 48 patients (18.9 %) developed SHG (IgG < 700 mg/dL), mostly asymptomatic (70.80 %) and mild (85.4 %). SHG was independently associated with lower baseline IgG levels (OR = 0.99 per unit increase; P = 0.001) and a standard interval dosing (SID) regimen (OR = 0.027, 95 % CI: 0.001–1.013, P = 0.051) in subgroup rituximab-treated patients. Serious infections occurred in 7.1 % of patients and were predicted by lower year-one IgG levels (OR = 0.98 per unit increase; P < 0.001). Conclusion: Our results revealed an 18.9 % incidence rate of SHG in MS patients treated with anti-rituximab and ocrelizumab, which was mainly asymptomatic and mild. We also demonstrated the lower baseline IgG levels and SID regimen as a risk factor to develop SHG. The incidence of SHG at year one was strongly associated with an increased risk of infection. Our findings underscore the IgG monitoring before and during anti-CD20 treatment, along with patient-tailored anti-CD20 regimens to mitigate the risk of SHG and infection. © 2025 Elsevier B.V.