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Real world predictors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab or ofatumumab for the treatment of multiple sclerosis: The REPLACE-MS study. Mult Scler 2026 Mar;32(3):338-346

Date

02/10/2026

Pubmed ID

41664431

DOI

10.1177/13524585251412125

Scopus ID

2-s2.0-105029583617 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

INTRODUCTION: Ocrelizumab (OCR) and ofatumumab (OFB) are disease-modifying therapies (DMTs) for multiple sclerosis (MS). Patients on these DMT's are at higher risk of hypogammaglobulinemia (HGG), which may increase the risk of infections.

OBJECTIVES: To investigate the impact of OCR and OFB and patient-specific, independent factors in developing HGG and serious infections.

METHODS: This multicenter, cohort retrospective study included patients who had received induction dosing with OCR or OFB. The primary outcome was the incidence and predictors of HGG.

RESULTS: A total of 911 patients (732 OCR, 179 OFB) were included. The mean (±SD) age was 45.4 (±12.8 years), and 68.6% were female. A total of 9.8% of patients developed HGG. Univariate analysis associated older age, Caucasian race, longer time on therapy, and lower baseline immunoglobulin G (IgG) levels as potential risk factors for HGG. Multivariable regression identified age ⩾50 years (p = 0.039), Caucasian race (p = 0.0002), and time on therapy ⩾3 years (p = 0.0094) as independent risk factors for HGG. Eight percent of patients experienced a serious infection. Multivariable regression identified HGG, lymphopenia, time on therapy ⩾3 years, previous DMT use, and progressive phenotype as independent risk factors for serious infection. A propensity-score-matching analysis found no differences in HGG and serious infection rates between OCR and OFB.

CONCLUSIONS: Age over 50, Caucasian race, time on therapy 3 or more years were risk factors for HGG.

Author List

Sangha KS, Jakubecz C, Maynard M, Hernandez RS, Esmaeili S, Zabeti A, Abboud H, Serra A, Woodson S, Obeidat AZ

Author

Ahmed Zayed Obeidat PhD, MD Associate Professor in the Neurology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Agammaglobulinemia
Antibodies, Monoclonal, Humanized
Female
Humans
Immunologic Factors
Incidence
Male
Middle Aged
Multiple Sclerosis
Retrospective Studies
Risk Factors