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Title:

Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis.

Document type:
journal article
Author(s):
Fox, RJ; Miller, DH; Phillips, JT; Hutchinson, M; Havrdova, E; Kita, M; Yang, M; Raghupathi, K; Novas, M; Sweetser, MT; Viglietta, V; Dawson, KT; CONFIRM Study Investigators; Fox, RJ; Phillips, J; Hutchinson, M; Havrdova, E; Kita, M; Wilson, K; Yang, M; Dawson, KT; Antel, J; Ware, J; Polman, C; Kowey, PR; Chung, R; Bakris, G; Richert, J; Seibert, B; Brandes, D; Brassat, D; Cohen, B; Diem, R; Goldman, M; Herndon, R; Miller, A; Tumani, H; Alfaro-Vidal, T; Crespo, C; Foster, J; Hunter, K; Garcia-Go...     »
Abstract:
BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing-remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate).In this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing-remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The study was not designed to test the superiority or noninferiority of BG-12 versus glatiramer acetate.At 2 years, the annualized relapse rate was significantly lower with twice-daily BG-12 (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice-daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate significantly reduced the numbers of new or enlarging T(2)-weighted hyperintense lesions (all P<0.001) and new T(1)-weighted hypointense lesions (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12 versus glatiramer acetate, differences were not significant except for the annualized relapse rate (thrice-daily BG-12), new or enlarging T(2)-weighted hyperintense lesions (both BG-12 doses), and new T(1)-weighted hypointense lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events (with BG-12) and injection-related events (with glatiramer acetate). There were no malignant neoplasms or opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG-12.In patients with relapsing-remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.).
Journal title abbreviation:
N Engl J Med
Year:
2012
Journal volume:
367
Journal issue:
12
Pages contribution:
1087-97
Language:
eng
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/22992072
Print-ISSN:
0028-4793
TUM Institution:
Neurologische Klinik und Poliklinik
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