Treatment with dimethyl fumarate, compared with teriflunomide, is associated with better clinical outcomes in patients with relapsing-remitting multiple sclerosis (MS), according to new research.

Time to disability worsening was longer for patients who received dimethyl fumarate, compared with those who received teriflunomide (hazard ratio [HR], 0.58).

“Our analysis of real-world data showed that in relapsing-remitting MS, dimethyl fumarate treatment was associated with more favorable clinical outcomes, compared to teriflunomide,” study author Jannis Müller, a research associate and doctoral candidate at the University of Basel, Switzerland, said during his presentation.

He described the results at the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2021.

Real-World Data

Dimethyl fumarate and teriflunomide, both oral treatments, reduce the relapse rate in patients with relapsing-remitting MS. Researchers have compared the efficacy of these drugs by analyzing observational data, and the results have been mixed. No head-to-head comparison had been performed.

“We aimed at contributing to this controversy by comparing the clinical outcomes on dimethyl fumarate and teriflunomide in a real-world setting, where both drugs are licensed as first-line treatment for relapsing-remitting MS,” said Müller. They examined data from the Swiss Federation for Common Tasks of Health Insurance, which includes more than 14,000 patients with MS.

The researchers identified all patients with relapsing-remitting MS who initiated or switched to dimethyl fumarate or teriflunomide between January 2013 and March 2019 for their analysis. They matched all patients at the time of treatment initiation on age, gender, disease duration, baseline Expanded Disability Status Scale (EDSS) score, time since last relapse, and relapse rate in the previous year.

The primary outcomes were time to relapse and time to 12-month confirmed EDSS worsening. The researchers analyzed these outcomes using pairwise, censored Cox proportional hazard models. For patients who switched from one drug to the other, they created mixed proportional hazard Cox models.

Slowed Disability Worsening

The investigators included 1625 patients in their analysis. Of this group, 1214 received dimethyl fumarate and 411 received teriflunomide. “Prior to matching, patients on dimethyl fumarate were younger, had a shorter disease duration, a lower EDSS, and a shorter time since last relapse,” said Müller.

The researchers matched 902 patients receiving dimethyl fumarate with 320 patients receiving teriflunomide. The two study arms were well matched on demographic and clinical variables. About 72% of participants were female, mean age was approximately 44 years, and median EDSS score was 2.0.

The primary analysis was based on 401 events in more than 3000 person-years. In the unmatched groups, time to relapse was similar between patients receiving dimethyl fumarate and those receiving teriflunomide.

In the matched analysis, however, time to relapse was longer in the dimethyl fumarate group, compared with the teriflunomide group (HR, 0.72; P = .03). This finding was confirmed in the weighted analysis (HR, 0.75; P = .02).

In the unmatched analysis, time to EDSS worsening was longer among patients receiving dimethyl fumarate, compared with those receiving teriflunomide (HR, 0.58; P < .01). Results in the matched and weighted analyses were similar.

Among 80 patients who switched from one drug to the other, time to relapse was longer during dimethyl fumarate treatment than during teriflunomide treatment (HR, 0.38; P = .01), regardless of the order in which the drugs were taken.

“A Solid Study”

“Given a real-world analysis, this is a pretty solid study,” said Anthony T. Reder, MD, professor of neurology at the University of Chicago, who commented on the findings for Medscape Medical News. Reder was not involved in the investigation.

Among the strengths of the study is its basis in a national registry that includes a large patient population, said Reder. The study population was primarily European, so the results cannot be generalized to Asian or African American patients. Nevertheless, the population reflects the majority of patients with MS, said Reder.

Another strength is the investigators’ decision to separate patients who switched therapies into a new group. It is unclear, though, how the investigators handled patients who switched from dimethyl fumarate or teriflunomide to a third therapy. “I assume they’re kicked out of the analysis,” said Reder.

But, as is the case with most matched cohort studies, certain relevant matching covariates appear to have been left out of this analysis. The investigators matched for age, sex, disease duration, severity score, last relapse, and relapse rate in the previous year, which are crucial variables. But they did not match patients on vitamin D levels, smoking, and BMI, “which are very important environmental factors in the course of MS,” said Reder.

In addition, the statistical analysis shows that the 400 patients who were not matched had more relapse activity than the matched patients. This difference may have contributed to the finding in the matched analysis that dimethyl fumarate was superior to teriflunomide on suppressing relapses, said Reder.

“However, the important measure here is progression: EDSS worsening,” he added. For that outcome, the hazard ratio is 0.58 in the unmatched and matched analyses. “That’s a pretty big decrease in this score, which is more solid than attack rate,” said Reder.

“The bottom line is that it looks like dimethyl fumarate is superior on a very important measure, which is worsening on the EDSS score,” he continued. But dropouts with active disease might have been more prevalent in the dimethyl fumarate group, compared with the teriflunomide group.

The study was funded by Biogen. Müller and Reder have disclosed no relevant financial relationships.

37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2021: Abstract P819. Presented October 14, 2021.

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