Thursday, May 03, 2007


Three-year data from the BENEFIT study suggest that, in patients with clinically isolated syndrome (CIS), immediate treatment with interferon (IFN) ß-1b significantly delays progression to clinically definite multiple sclerosis (CDMS). These findings provide further evidence that early treatment, even when administered at the first event suggestive of MS, provides long-term benefits for patients. In the BENEFIT study, 468 CIS patients with MRI findings suggestive of MS were treated with subcutaneous IFN ß-1b (250 µg; n=292) or placebo (n=176) every other day until either a diagnosis of CDMS was attained or they reached 2 years of evaluation. Patients were then eligible to receive open-label IFN ß-1b for up to 5 years after start of double-blind treatment. According to Mark Freedman, University of Ottawa, Ottawa, Canada, this is the first prospectively planned, controlled, multicenter trial to address the impact of randomly assigned immediate vs later initiation of IFN ß-1b (250 µg) therapy at the time of CIS on the further evolution to MS. A total of 418 patients have enrolled in the open-label phase of the study, 261 of whom were previously treated with IFN ß-1b (96%); 157 of whom were previously treated with placebo. Three years after the start of the double-blind study, 37% of those who had received IFN ß-1b from the start and 51% of those who originally received placebo had fulfilled the criteria for CDMS, reported Dr. Freedman. In addition, confirmed Expanded Disability Status Scale (EDSS) progression was seen in 16% of early treatment patients, compared with 24% of delayed treatment patients; this corresponded to a 40% risk reduction after 3 years ( P=0.0218). Differences in EDSS scores did not appear to be affected by changes in relapse rates between the 2 groups.

Comment-- this study has the same pitfalll as the other extension studies in multiple sclerosis with a biased sample for inclusion in the extension trial. Biases include selection bias and others.   

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Neurodoc said...

Marketing says 85 % subjects progressed to MS within two years. Actually, this is McDonald MS using the g more liberal MRI criteria. In BENEFIT, 85 % of placebo developed McDonald MS, v. 69 % of treated group, and 45 % developed CDMS v. 28 % of placebo.

The risk of CDMS after CIS ranges from 51 % in the ONTT among subjects having 3 + brain lesions (and 16 % in those who did not) to 80 % in patients followed for 14 years (NEJM 2002 first author BREX).

Neurodoc said...

Compare to CHAMPS: Half of the patients in CHAMPS developed CDMS or had new lesions (McDonald MS) at 2 years. Since 69 % of patients developed McDonald's MS at two years, one cannot claim these data even suggest superiority of Betaseron, au contraire.

Neurodoc said...

Real impressive part of BENEFIT for me was that 93 % of subjects finished the trial (higher than prior Betaseron trials in which the dropouts numbered in the high teens) and that depression was less than placebo. In all Betaseron trials, there are 3 suicides and 8 attempts among 1532 patients v. 5/965 placebo (not significant statistically).