Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis (CROSBI ID 201343)
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Podaci o odgovornosti
Gold, Ralf ; Kappos, Ludwig ; Arnold, Douglas L. ; Bar-Or, Amit ; Giovannoni, Gavin ; Selmaj, Krzysztof ; Tornatore, Carlo ; Sweetser, Marianne T. ; Yang, Minhua ; Sheikh, Sarah I. ; Dawson, Katherine T. ; ... ; Brinar, Vesna ; Demarin, Vida ; Rudež, Josip ; Soldo-Butković, Silva ; Baraba Vurdelja, Ranka
DEFINE Study Investigators
engleski
Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis
BG-12 (dimethyl fumarate) was shown to have antiinflammatory and cytoprotective properties in preclinical experiments and to result in significant reductions in disease activity on magnetic resonance imaging (MRI) in a phase 2, placebo-controlled study involving patients with relapsing-remitting multiple sclerosis. We conducted a randomized, double-blind, placebo-controlled phase 3 study involving patients with relapsing- remitting multiple sclerosis. Patients were randomly assigned to receive oral BG-12 at a dose of 240 mg twice daily, BG-12 at a dose of 240 mg three times daily, or placebo. The primary end point was the proportion of patients who had a relapse by 2 years. Other end points included the annualized relapse rate, the time to confirmed progression of disability, and findings on MRI. The estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group (27% with BG-12 twice daily and 26% with BG-12 thrice daily vs. 46% with placebo, P<0.001 for both comparisons). The annualized relapse rate at 2 years was 0.17 in the twice-daily BG-12 group and 0.19 in the thrice-daily BG-12 group, as compared with 0.36 in the placebo group, representing relative reductions of 53% and 48% with the two BG-12 regimens, respectively (P<0.001 for the comparison of each BG-12 regimen with placebo). The estimated proportion of patients with confirmed progression of disability was 16% in the twice-daily BG-12 group, 18% in the thrice- daily BG-12 group, and 27% in the placebo group, with significant relative risk reductions of 38% with BG-12 twice daily (P=0.005) and 34% with BG-12 thrice daily (P=0.01). BG-12 also significantly reduced the number of gadolinium-enhancing lesions and of new or enlarging T(2)-weighted hyperintense lesions (P<0.001 for the comparison of each BG-12 regimen with placebo). Adverse events associated with BG-12 included flushing and gastrointestinal events, such as diarrhea, nausea, and upper abdominal pain, as well as decreased lymphocyte counts and elevated liver aminotransferase levels. In patients with relapsing-remitting multiple sclerosis, both BG-12 regimens, as compared with placebo, significantly reduced the proportion of patients who had a relapse, the annualized relapse rate, the rate of disability progression, and the number of lesions on MRI. (Funded by Biogen Idec ; DEFINE ClinicalTrials.gov number, NCT00420212.).
oral BG-12 ; relapsing multiple sclerosis
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Podaci o izdanju
367 (12)
2012.
1098-1107
objavljeno
0028-4793
1533-4406
10.1056/NEJMoa1114287
Povezanost rada
Kliničke medicinske znanosti