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

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.