The gastroresistant capsules are taken twice daily with food. The starting dose is 120mg twice daily, increasing after 7 days to 240mg twice daily.
"Tecfidera has the advantage of being a capsule and is an efficacious and convenient oral therapy," said Dr Eli Siber, consultant neurologist at the King's Regional Neurosciences Centre in London. "This treatment has been available in the United States since the summer of 2013 and it is excellent news that appropriate patients in the UK will also have the opportunity to be treated."
Dimethyl fumarate is believed to reduce inflammation via the Nrf2-dependent antioxidant pathway, although its exact mechanism of action is not fully understood.1
Lower relapse rate
In DEFINE, the proportion of patients who relapsed within 2 years (the primary endpoint) was significantly lower among those treated with dimethyl fumarate twice daily (n=410) than among those who received placebo (n=408): 27% versus 46% (p<0.001), translating into a 49% relative reduction with dimethyl fumarate.2
Reduced progression of disability
The annualised relapse rate at 2 years was 0.17 in the twice-daily dimethyl fumarate group compared with 0.36 in the placebo group, representing a relative reduction of 53% (p<0.001). The proportion of patients with 12-week confirmed progression of disability (as measured by the Expanded Disability Status Scale [EDSS]) was also significantly lower with dimethyl fumarate twice daily than placebo at 2 years, at 16% and 27% respectively (relative reduction of 38%; p=0.005).2
The primary endpoint in CONFIRM was the annualised relapse rate at 2 years, which was reduced by 44% (p<0.001) with dimethyl fumarate twice daily (n=359) compared with placebo (n=363), from 0.40 to 0.22. The annualised relapse rate with glatiramer acetate (n=350), included as an active reference comparator, was 0.29. Patients who received dimethyl fumarate also had a lower rate of relapse at 2 years than those given placebo (34% relative reduction, p=0.0020). There was a non-significant 21% reduction in the risk of 12-week confirmed disability progression compared with placebo at 2 years.3
Fewer brain lesions
MRI scans showed that dimethyl fumarate significantly reduced the number of gadolinium-enhancing lesions and new or enlarging T2-weighted hyperintense lesions at 2 years in both studies (p<0.001 vs placebo for all comparisons).2,3
The most common adverse events associated with dimethyl fumarate were flushing and GI reactions (including diarrhoea, nausea and abdominal pain), which led to discontinuation in approximately 3% and 4% of patients, respectively.2,3
Mean lymphocyte counts decreased during the first year of treatment and then plateaued. No opportunistic infections occurred in patients who received dimethyl fumarate and the overall incidence of serious infections in the dimethyl fumarate groups was comparable to that in the placebo groups.2,3
The long-term safety and efficacy of dimethyl fumarate are being investigated in ENDORSE, a 5-year extension of DEFINE and CONFIRM.
- Tecfidera Summary of Product Characteristics, January 2014.
- Gold R et al. N Engl J Med 2012; 367: 1098-107.
- Fox RJ et al. N Engl J Med 2012; 367: 1087-97.
Further information: Biogen Idec