Results of the CONFIRM and DEFINE studies suggest that dimethyl fumarate (BG-12) should be considered as an oral treatment for patients with relapsing-remitting multiple sclerosis (MS).
Both studies appeared in TheNew England Journal of Medicine.
The Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study authors investigated the efficacy and safety profile of oral BG-12 as compared with placebo in patients with relapsing-remitting multiple sclerosis. Glatiramer acetate was also included as a reference comparator.
A total of 1417 patients were included in the phase III trial. They were randomly assigned to receive oral placebo, BG-12 at a dose of 240 mg two or three times daily, or subcutaneous daily injections of 20 mg glatiramer acetate for 96 weeks.
The team, led by Robert Fox (Cleveland Clinic, Ohio, USA), found that twice- and thrice-daily treatment with BG-12 reduced the annualized relapse rate by 44% and 51%, respectively, as compared with placebo. It also reduced the estimated proportion of patients with a relapse from 41% with placebo to 29% and 24% with the two doses of BG-12, respectively.
There were also fewer MS lesions on magnetic resonance imaging (MRI) scans in patients who received BG-12 than in those who received placebo.
In the Determination of the Efficacy and Safety of Oral Fumarate in Relapsing Remitting Multiple Sclerosis (DEFINE) study, Ralf Gold (Ruhr-University Bochum, Germany) and colleagues randomly assigned 1237 patients to receive oral BG-12 at a dose of 240 mg twice daily or three times daily, or placebo.
At 2 years, treatment with BG-12 two or three times per day reduced the annualized relapse rate by 53% and 48%, respectively, as compared with placebo. The estimated proportion of patients with a relapse was also reduced, from 46% of patients treated with placebo 27% and 26%, respectively.
Similar to the CONFIRM study, there were also fewer MS lesions on MRI scans in patients who received BG-12 than in those who received placebo.
"These findings support BG-12 as a potential initial oral treatment for patients with relapsing-remitting MS or as an alternative to currently available therapies," say Fox et al.
However, in an accompanying editorial Allan Ropper, from Brigham and Women's Hospital in Boston, Massachusetts, USA, cautions that more long-term safety and efficacy outcomes will be required to satisfy clinicians.
"Because published trials are designed mainly for approval of a drug by the Food and Drug Administration or the European Medicines Agency, comparisons to placebo and findings such as a reduction in annualized relapse rates over a period of 1 or 2 years, a reduction in lesions on MRI, and a longer time to worsening on a disability scale all make new drugs look favourable in the short run," he writes. "But the average age at onset of [MS] is in the late 20s, and it typically results in disability only after 15 to 20 years."
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