Tecfidera (dimethyl fumarate) is safe and effective as a long-term treatment for relapsing-remitting multiple sclerosis (RRMS), a study of clinical trial data covering up to 11 years of treatment suggests.
The study, “Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE,” was published in the journal Therapeutic Advances in Neurological Disorders.
Tecfidera is approved by the U.S. Food and Drug Administration as an oral treatment for relapsing forms of multiple sclerosis (MS), including RRMS, clinically isolated syndrome (CIS), and active secondary progressive MS (SPMS). It is believed to work by reducing the activity of the immune system.
Data from two Phase 3 studies, DEFINE (NCT00420212) and CONFIRM (NCT00451451), demonstrated the efficacy of Tecfidera, relative to a placebo, in people with RRMS. People who completed these placebo-controlled trials could enroll in an extension study called ENDORSE (NCT00835770), which evaluated Tecfidera’s effectiveness and safety (240 mg capsules twice daily) over years of use.
Researchers here report data from ENDORSE, with a total median follow-up time of nine years (two in the initial trials plus seven in the extension study), with some patients treated for up to 11 years. In total, 1,736 people who completed DEFINE or CONFIRM were enrolled in ENDORSE.
Data showed that Tecfidera treatment effectively prevented relapses in participants. For those given Tecfidera in the initial trials, the annual relapse rate (ARR) ranged from 0.20 relapses/year in the first year to 0.09 relapses/year by eight to nine years of follow-up.
For those initially given placebo — patients who were switched to Tecfidera after enrolling in ENDORSE — initial ARR was 0.35 relapses/year, dropping to less than 0.16 in years three to nine of the ENDORSE study. In this group, “a decreased ARR was apparent as early as year 3–4, and some reduction in ARR continued year-over-year throughout the treatment period,” the researchers wrote.
Over a total of about nine years, about half of ENDORSE patients remained relapse-free — 53% of those initially given Tecfidera and 47% of those initially on a placebo who switched to Tecfidera. In total, 86% of ENDORSE participants had two or fewer relapses.
At the start of ENDORSE trial, the average score on the expanded disability status scale (EDSS) was 2.3 for those given Tecfidera in DEFINE/CONFIRM, and 2.5 for those given placebo in these trials. (A higher EDSS score indicates a greater disability level.) After about seven years of treatment, the average EDSS scores remained stable: 2.4 and 2.6, respectively, for these patient groups.
At year nine, over 80% of participants, regardless of initial treatment, had EDSS scores of less than four, indicating no impairment in walking ability.
Relapse and EDSS findings were consistent in the subgroup of patients newly diagnosed with MS at the time they enrolled in DEFINE or CONFIRM.
“Taken together, these findings suggest that long-term treatment with DMF [Tecfidera] allows patients to maintain a relatively low rate of relapse and maintenance of walking abilities,” the researchers wrote.
In about 70% of ENDORSE participants, no evidence of new or enlarging lesions on MRI scans were seen after nine years.
“The radiological data reported herein suggest that long-term DMF treatment translates into meaningful benefits of brain tissue protection,” the researchers wrote.
Regarding safety, results from ENDORSE did not indicate any new or unexpected safety concerns associated with long-term Tecfidera use that were not noted in earlier studies. Most (94%) participants reported at least one adverse event. About a third (30%) reported at least one serious adverse event, the most common being MS relapses, falls, and urinary tract infections.
About 11% had abnormal liver enzyme readings, and 25% had kidney-associated adverse events — findings generally consistent with the known safety profile of Tecfidera. About 3% of participants were diagnosed with a cancer, which is consistent with the cancer rate in the general U.S. population.
Less than 5% of participants reported serious infections. These are a concern because Tecfidera weakens the immune system, potentially leaving a person more susceptible to infections.
A separate analysis of 2,470 people from these trials suggested that prolonged lymphopenia (low levels of infection-fighting immune cells called lymphocytes) was not associated with an increased infection risk. This analysis also demonstrated that, in individuals who developed lymphopenia, lymphocytes generally returned to normal levels within some three months of stopping Tecfidera.
“The safety and efficacy profile observed in this analysis for up to 11 years further supports DMF as a valuable long-term treatment option for patients with RRMS, including those newly diagnosed with MS,” the researchers concluded.
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