Comparison of Relapse Rates for Disease-Modifying Therapies for Multiple Sclerosis Using Real-World Data

February 2022

Clinicians have a number of options for disease-modifying therapies (DMTs) to slow the progression of multiple sclerosis (MS). Because it is unclear which therapies are most effective, Xia and colleagues conducted a comparative effectiveness study. DMTs can be divided into lines as standard-efficacy DMTs or high-efficacy DMTs so the investigators chose to compare within treatment lines. Dimethyl fumarate and fingolimod are standard-efficacy DMTs while natalizumab and rituximab are high-efficacy DMTs. All 4 are commonly prescribed.

Patients were participants in the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) at Brigham and Women’s Hospital. Data from CLIMB participants were integrated with corresponding electronic health records (EHRs). The treatment group assignment was the first therapy initiated for dimethyl fumarate or fingolimod when there was no prior high-efficacy DMT therapy. For the high-efficacy comparison, treatment group assignment was the first therapy initiated for natalizumab or rituximab regardless of whether a standard-efficacy therapy was previously used. The primary outcomes were clinical or radiologic relapse at year 1 and year 2 and time to relapse.

In a real-world retrospective study, selection among treatment options is dependent on patient characteristics, which can lead to differences between groups from baseline. Access to EHRs gave investigators the ability to perform multistep adjustments for confounders not normally available from registry data. These confounders included age of first MS classification code, disease duration, and the number of relapses in the prior 1 or 2 years, among others.

For the standard-efficacy DMT comparison, the investigators found similar relapse rates and time to relapse for initiation of dimethyl fumarate compared with initiation of fingolimod. For the high-efficacy DMT comparison, the investigators found that patients who initiated natalizumab had higher relapse rates and shorter time to relapse compared with the patients who initiated rituximab. The differences between natalizumab and rituximab groups were revealed only after correcting for confounders.

Limitations pointed out by investigators included the relatively low level of relapse rates in CLIMB participants and the use of treatment initiation for treatment group assignment because of the inability to measure treatment adherence.

The investigators put forward several implications from the study for MS treatment in particular and the comparative effectiveness field in general. “These findings based on high-dimensional modeling that incorporates EHR data address knowledge gaps in MS treatment guidance where randomized clinical trials are unavailable and likely infeasible,” they stated. The investigators claimed that their approach could be a model for other real-world comparison studies when detailed EHRs are available.


Hou J, Kim N, Cai T, et al. Comparison of dimethyl fumarate vs fingolimod and rituximab vs natalizumab for treatment of multiple sclerosis. JAMA Netw Open. 2021;4:e2134627.

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