Ocrelizumab Led to Declines in Immunoglobulins in Patients With MS

Declines in immunoglobulins were found in patients living with multiple sclerosis (MS) when they used ocrelizumab (OCR) to treat the condition, according to a study in Neurological Research and Practice.¹ The results indicate that patients with low baseline levels of immunoglobulins should be monitored for intervention.

OCR is a treatment used to treat MS in patients through the slowing of disability progression in the relapsing-remitting (RRMS) and primary progressive (PPMS) forms of MS.² The treatment works to rapidly deplete B cells, which could have effects on patients in the long term as immunoglobulin (Ig) levels decrease. The risk of infection due to this occurrence is unknown, however. This study aimed to use a real-world cohort to assess changes in serum IgG, IgA, and IgM for patients using OCR to treat their MS.¹

This observational study was performed at a single center in Germany that specializes in the management of MS. Patients were included in the study if they had a diagnosis of RRMS or PPMS, were 18 years or older, and had received treatment with OCR between February 1, 2018, and April 30, 2023. Patients who had started OCR outside of the study center, had prior therapy with other treatments that depleted B cells, had fewer than 2 measurements for Ig, or had fewer than 2 treatment cycles with OCR were excluded from the study.

All participants had a neurological exam an estimation of walking distance, and were scored on the Expanded Disability Severity Scale (EDSS) at baseline. OCR was given in two 300-mg doses that came 2 weeks apart before moving to a 600-mg dose every 6 months. Follow-up visits were scheduled every 2 to 6 months with the neurologist after the start of treatment. The researchers collected electronic health record data from the hospital, including sociodemographic data and disease-related parameters.

There were 116 patients included in the final analysis, including 9 patients who discontinued treatment with OCR. The patients were primarily women (60%) and had a diagnosis of RRMS (81%). Treatment with OCR was started at a median (IQR) age of 39 (30-52) years after an onset of MS at a median of 28 (23-41) years. Median EDSS was 2.5 (1.0-4.5) at baseline, and psychiatric disorders were the most common comorbidity (47%).

Disease activity based in MRI saw a decline after the start of OCR treatment (OR, 0.29; 95% CI, 0.19-0.44). Active MRI lesions decreased from 60% before treatment to 20% in the first year. A third of the patients with RRMS and PPMS experienced disability progression of an EDSS increase of 1 or more points. Patients with RRMS (OR, 1.31; 95% CI, 0.95-1.82) or PPMS (OR, 1.27; 95% CI, 0.80-2.00) had no association between EDSS progression and increasing treatment years.

IgG declined gradually in the 107 patients with available baseline Ig values. These reductions were more pronounced in the fifth and sixth cycles and reached 17.9% in the ninth and 10th cycles. IgM declined more and reached 31.0% by the ninth and 10th cycles. IgG declined by 1.0% per cycle, whereas IgM declined by 6.1% per cycle. IgA declined by 1.7% per cycle. Patients with lower baseline levels did not have a disproportionate decline compared with patients with higher baseline levels. A total of 29.3% of patients reported at least 1 infection, with the most common being a urinary tract infection.

There were some limitations to this study. Generalizability and causality were limited due to the retrospective design and smaller sample size. Exposure-time bias is possible due to the time-dependent nature of some of the analyses. Measures of Ig used serum concentrations rather than functional antibody responses or cellular immune competence. There is also no standard definition of low Ig and affects comparison of reported rates of immunoglobulin across analyses. There was a higher proportion of corticosteroid pulse therapies administered to the patients.

“This real-world longitudinal study demonstrates that OCR induces predicatable, class-specific declines in serum Ig levels…” the authors concluded. “While hypogammaglobulinemia—particularly of IgM—is common, no clear association with short- to mid-term infection risk was observed…”

References

1. Bohn A, Teubner FS, Tauber SC, Waschbisch A. Longitudinal changes of serum immunoglobulins under ocrelizumab: factors associated with hypogammaglobulinemia and infection risk in a real-world multiple sclerosis cohort. Neurol Res Pract. 2026;8(1):52. doi:10.1186/s42466-026-00509-0
2. Ocrelizumab injection. Cleveland Clinic. Accessed June 30, 2026. https://my.clevelandclinic.org/health/drugs/18442-ocrelizumab-injection