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

Background: Disease-modifying treatments (DMTs) for multiple sclerosis (MS) reduce inflammation in the central nervous system. Risk stratification for infections while on DMTs remains challenging. It is unknown if and how estimated risks of infection of DMTs compare between trials and observational studies.

Objectives: The aim of this systematic review was to provide a comprehensive overview of observational study data of the risk of infection in people with MS using DMT.

Methods: PubMed and Embase were searched for observational studies published on or before 4 April 2023 describing the occurrence of infection in people with MS, in which at least 2 DMTs were compared to each other or at least 1 DMT to no DMT. Records were screened using the machine learning algorithm ASReview. We examined which DMT contrasts (i.e., DMT A vs. DMT B) and infection types were studied and in how many studies. The risk of bias in each study with relative risk of infection was assessed using the ROBINS-I tool. For the most frequently studied DMT, the reported findings were compared to findings from a recent clinical trial data based network meta-analysis regarding this topic.

Results: Out of 5373 search records 22 papers were included, of which 5 reported relative risks of infection; the other studies only provided counts or rates. In total, 9 different DMTs were studied: alemtuzumab, beta-interferon, cladribine, dimethyl fumarate, fingolimod, glatiramer acetate, natalizumab (NAT), ocrelizumab, and teriflunomide. The distribution of the number of studies over the 45 possible contrasts was: 9 contrasts not studied, 19 contrasts once, 4 contrasts twice, 5 contrasts 3 times, 2 contrasts 4 times, 4 contrasts 5 times, and 2 contrasts 6 times. The most assessed infection types were any (n = 14), neurological (n = 11), and respiratory (n = 9). Out of those studies providing relative risks, 3 were scored as moderate risk of bias and 2 as serious. NAT was the most studied DMT contrasting 5 other DMTs; observational data for natalizumab (NAT) versus another DMT for 8 infection types were available for 20 of the 40 possible combinations. Observational findings on any, respiratory, and urinary infection could be compared to trial data for 10 combinations: associations were 3 times in similar direction, 4 times in opposite direction, one time observational data were contradictory, one time trial data were contradictory and once there were 0 events in the observational study.

Conclusions: Observational study data of the risk of infection in people with MS on DMT are scarce. 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.