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Observational Study
. 2025 May 22;272(6):415.
doi: 10.1007/s00415-025-13133-w.

Real-world observational study of infections in people treated with ocrelizumab for multiple sclerosis

Laura Davies  1 , Rasheed Shehadeh  2 , W John Watkins  2 , Stephen Jolles  2   3 , Neil P Robertson  1   4 , Emma C Tallantyre  5   6
Affiliations
Observational Study

Real-world observational study of infections in people treated with ocrelizumab for multiple sclerosis

Laura Davies et al. J Neurol. .

Abstract

Background: Anti-CD20 monoclonal antibodies are now a common first-line treatment for multiple sclerosis (MS). Rituximab, ocrelizumab and ofatumumab have all been associated with a dose-dependent risk of hypogammaglobulinaemia, but its relevance in clinical practice remains uncertain.

Objectives: To study infection rates over time in a real-world cohort of people treated with ocrelizumab for MS, and their relationship to serum immunoglobulin.

Design: Observational study of 152 people receiving ocrelizumab for MS followed for up to 5.6 years (mean 2.7 years).

Results: Mean (SD) annualized changes in immunoglobulins during ocrelizumab treatment were IgM - 0.22 g/L/year (0.4), IgG - 0.38 g/L/year (0.9), IgA - 0.03 g/L/year. Rates of self-reported infection increased significantly during the first 4 years of treatment. Infection rates were not only associated with total immunoglobulin levels but also independently associated with age, comorbidity and female sex. We demonstrated for the first time that 29 out of 34 (87%) people on ocrelizumab with IgG in the lower normal range had sub-protective antibody responses to pneumococcus / haemophilus influenzae.

Conclusions: Real-world observational studies complement open label extensions of clinical trials, often by having a more representative cohort and more complete follow-up. Our data suggest that while serious infections are rare in people on ocrelizumab, non-serious infections become increasingly burdensome. We offer practical suggestions on mitigating the risk of infection on ocrelizumab and other anti-CD20 medications.

Keywords: Disease modifying therapy; Hypogammaglobulinaemia; Multiple sclerosis; Ocrelizumab; Treatment complications.

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Conflict of interest statement

Declarations. Conflict of interest: In the last 5 years ET has received honorarium for consulting work from Biogen, Janssen, Merck, Novartis, and Roche. She has received travel grants to attend or speak at educational meetings from Biogen, Merck, Neuroax, Roche, and Novartis. SJ has received support for conferences, speaker, advisory boards, trials, data and safety monitoring boards, studies and projects with CSL Behring, Takeda, Octapharma, Grifols, BPL, LFB, Kedrion, Pharming, Biocryst, Capitainer, Swedish Orphan Biovitrum, Biotest, Binding Site, GSK, Sanofi, UCB Pharma and HCRW. LD, RS, WJW report no conflicts of interest. Ethical statement: This human study has been approved by a UK research ethics committee and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

Figures

Fig. 1
Fig. 1
Immunoglobulins and infections over time. a–c Change in IgG, IgA and IgM over time by 6-month infusion interval. Vertical lines indicate standard error. Sample size at each infusion (n) and % with Ig below the lower limit of normal (LLN) shown below the x-axis, d violin plot of infection count over time by 6-month infusion interval. Number under follow-up (n) at each time point is shown below the x-axis
Fig. 2
Fig. 2
Immunoglobulin over time according to ocrelizumab treatment schedule. IgM (a) and IgG (b) over time in 14 people who had standard interval dosing (SID; shown in black), followed by extended interval dosing (EID, show in red) of ocrelizumab
Fig. 3
Fig. 3
Disease-specific IgG titres in people with low-normal total IgG on ocrelizumab. Box plot showing IgG titres to pneumococcus (a) and haemophilus influenza B (b) in people on ocrelizumab who have total IgG between 6 and 8 g/L. Horizontal line indicates median, whiskers are interquartile range. Red dashed line indicates protective cut-off
Fig. 4
Fig. 4
Infection types over time on ocrelizumab. Infection rates (per person per 6-month dose interval) over time in people on ocrelizumab. LRTI lower respiratory tract infection, URTI upper respiratory tract infection, UTI urinary tract infection
See this image and copyright information in PMC

References

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