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. 2025 Jun;46(6):2555-2569.
doi: 10.1007/s10072-025-08018-9. Epub 2025 Feb 8.

The relative risk of infection in people with multiple sclerosis using disease-modifying treatment: a systematic review of observational studies

M W Y Leung  1 , E M W Van de Garde  1 , B M J Uitdehaag  2 , O H Klungel  1 , M T Bazelier  3
Affiliations

The relative risk of infection in people with multiple sclerosis using disease-modifying treatment: a systematic review of observational studies

M W Y Leung et al. Neurol Sci. 2025 Jun.

Abstract

Background: Some disease-modifying treatments (DMTs) for multiple sclerosis (MS) increase the risk of infection, but it remains unknown how the risk compares between trials and observational studies.

Objective: To assess the current state of observational research on the risk of infection in people with MS and using DMTs.

Methods: PubMed and Embase were searched for observational studies published on or before 4 April 2023 describing infection in people with MS, with a comparison of at least 1 DMT to no DMT or another DMT. We examined which DMT contrasts and types of infection were studied and how often; and compared observational results of the most frequently studied DMT to trial data from a network meta-analysis.

Results: Out of 5373 search records 22 papers were eligible, of which 5 reported relative risks (RRs). In total, 9 DMTs were studied. Out of 45 possible contrasts, 9 were not studied, and 19 once. The most assessed specific type of infection was neurological (n = 11/22 studies). Natalizumab was the most studied DMT contrasting 7 other DMTs or no DMT, with 12 RRs reported. Point estimates of the RRs (compared to no DMT) for respiratory and urinary tract infections were in opposite direction compared to trial data.

Conclusion: Observational study data on the risk of infection in people with MS on DMT are sparse. The growing availability of real-world data on MS and DMT use provides an opportunity to study specific infections on DMT, which is particularly valuable to populations underrepresented in trials.

Keywords: Disease-modifying treatment; Infections; Multiple sclerosis; Observational research; Systematic review.

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Conflict of interest statement

Declarations. Ethical approval: Ethics approval was not applicable to this study because it was based exclusively on published literature. Competing interests: BU has received consultancy fees from Immunic Therapeutics. The other authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Flowchart of study inclusion
Fig. 2
Fig. 2
Risk of bias assessment for each included study with relative risk reported
Fig. 3
Fig. 3
Distribution of disease-modifying treatment (DMT) contrasts over observational studies reporting on the occurrence of infections on DMT, by contrast in DMT exposure. A black diamond indicates that a relative risk measure was reported at least once. Studies reporting multiple DMT contrasts contributed to the respective multiple matrix cells. DMT exposure categories comprising multiple DMTs contributed to each contrast in the matrix that was possible through the component DMTs
Fig. 4
Fig. 4
Infection risk on one of seven disease-modifying treatment (DMT) exposure categories compared to infection risk on natalizumab (NAT), from observational studies versus a recent network meta-analysis. If an observational study or the meta-analysis reported multiple outcomes or dosages belonging to a selected infection type or DMT, each result was included separately and represented by a triangle or circle
See this image and copyright information in PMC

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