Dimethyl Fumarate Safe, Effective Against Relapsing-Remitting MS in New Long-term Results

A new study that looks at the long-term effects of dimethyl fumarate finds the therapy is safe and effective in patients with relapsing-remitting multiple sclerosis who have taken the therapy for approximately a decade.

Delayed-release dimethyl fumarate (DMF) appears to be a safe and effective long-term treatment option for patients with relapsing-remitting multiple sclerosis (RRMS), according to new research.

Those findings are the result of a long-term extension study called ENDORSE. The results were published in the journal Therapeutic Advances Neurological Disorders.1

DMF, which is sold under the brand name Tecfidera, is approved for patients with relapsing MS, clinically isolated syndrome, and secondary progressive MS. The drug was found to be effective in the phase 3 DEFINE2 and CONFIRM3 studies, but in the new study, corresponding author Catherine Miller, PharmD, MPH, of Biogen Inc., and colleagues reported on the drug’s performance at approximately 9 years after patients began taking the regimen. Biogen is the manufacturer of Tecfidera. A total of 1736 patients who completed the DEFINE or CONFIRM studies enrolled in the new study, and 530 were in a cohort that received annual MRI evaluations. The enrollees included patients who took DMF from the start of their original study, and patients who were given placebo for the first 2 years and subsequently switched to DMF.

Miller and colleagues looked at a series of metrics, including incidence of serious adverse events, discontinuation due to adverse events, annualized relapse rate, and expanded disability status scale (EDSS) score.

Overall, 30% (527) of patients experienced serious adverse events, which were mostly falls and urinary tract infections. Adjusted annual relapse rate was ≤0.20 over 9 years of treatment. Patients in the placebo group saw drops in relapses beginning in year 3. Of those on DMF for their entire study, 73% had no 24-week confirmed disability progression; of those who took placebo for the first 2 years, the rate was virtually identical, at 74%.

Seven in 10 patients had no new T1 or new/newly enlarging T2 lesions after 7 years of treatment with DMF. Median percentage brain volume change after 6 years of treatment in ENDORSE was —1.32%, and severe prolonged lymphopenia was reported in just 53 patients among the 2470 patients who had at least 1 post-baseline measurement.

“These results demonstrate that, similar to what was observed in the pivotal DEFINE and CONFIRM trials, after up to 11 years of DMF treatment in ENDORSE, long-term DMF exposure has not resulted in any new or unexpected safety findings,” Miller and colleagues wrote.

The authors pointed out that the annual relapse rate remained low over the entire period of the ENDORSE study, and most patients who experienced a relapse experienced only one. EDSS scores remained stable; the majority of patients were walking without impairment or assistance at the end of the 9-year period, Miller and colleagues said.

The authors cautioned that because the present study is an extension study, it does not include patients who discontinued treatment in their original study, and therefore the results are not necessarily applicable to the entire original study population. However, the authors also noted that most patients who discontinued treatment did so for reasons of patient preference, rather than safety concerns.

In summary, Miller and colleagues said the findings offer further evidence to support the long-term use of the drug, including in patients who are newly diagnosed with MS.


  1. Gold, R., Arnold, D. L., Bar-Or, A., et al. Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE. Ther Adv Neurol Disord. doi:10.1177/1756286420915005
  2. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012; 367: 1098-1107. doi:10.1056/NEJMoa1114287
  3. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012; 367: 1087-1097. doi:10.1056/NEJMoa1206328