Interferon beta-1b Promising in Delaying Progression for Patients at Very Beginning of Multiple Sclerosis

 BRUSSELS, BELGIUM –

August 28, 2007 –

Interferon beta (IFNB)-1b therapy provides clinically relevant and statistically significant benefits in delaying disability progression for patients with a clinically isolated syndrome (CIS) presenting with their first demyelinating event, say researchers, and this finding supports the value of early treatment with IFNB-1b after the very first CIS event suggestive of multiple sclerosis (MS).

 This prospectively-planned, 3-year integrated analysis from the BENEFIT (Betaferon®/Betaseron® in Newly Emerging Multiple Sclerosis for Initial Treatment) 2-year, multicentre, randomised, double-blind, placebo-controlled study was presented on behalf of the BENEFIT Study Group by Hans-Peter Hartung, MD, Member of the Steering Committee, Professor and Chairman, Department of Neurology, University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany, here on August 27th at the 11th Congress of the European Federation of Neurological Societies (EFNS).

 Dr Hartung stressed initially that the BENEFIT trial is the first prospectively-planned study to address the impact of both high- dose, high-frequency therapy with IFNB-1b and early versus delayed initiation of IFNB-1b therapy in patients with a CIS indicative of MS. Therefore, there was an initial, double-blind, placebo-controlled phase (N = 468), and following a second event or 2 years of treatment, all patients were encouraged to continue into a further 3 years of follow-up with IFNB-1b. Of importance, "Patients and investigators remain blinded as to the initial randomisation period throughout the entire 5 years that this trial extends to," added Dr Hartung.

 Initial randomisation was to placebo (n = 168) or IFNB-1b (n = 292; 250 microg SC, every other day). Among this group, 94% and 93%, respectively, completed the study and, in both cases, 89% entered the follow-up. Thus, Dr Hartung was reporting on the 3-year integrated analysis that included 81% and 85%, respectively, of the original patient groups, with the former classified as 'delayed' IFNB-1b therapy (n = 157; mean age, 30 years), and the latter as 'early' (n = 261; mean age, 30 years).

 The key baseline clinical characteristics of these two groups were not different (delayed vs. early): T2 lesions, 17 versus 18; Gd- enhancing lesions, 0 versus 0; Expanded Disability Status Scale (EDSS) score at screening, 2 versus 2. Furthermore, this analysis was not biased by differential dropouts from these delayed versus early treatment groups.

 Primary outcome measures were time to clinically definite MS (CDMS) and demonstrated a risk reduction for early IFNB-1b treatment of 41% over 3 years (hazard ratio [HR], 0.59; log rank P =.0011). Similarly, time to confirmed EDSS progression showed a risk reduction of 40% over 3 years (HR, 0.60; log rank P =.0218). In further sensitivity analyses, there were similar risk reductions of around 40% for various categories of unscheduled visits.

 Of note, although showing a trend in favour of the early treatment of these patients with CIS for year 3, the patient-reported quality of life measure according to the Family Assessment of MS – Trial Outcome Index (FAMS-TOI) showed no differential impact over the first 2 years. Similarly, the patient-reported quality of life according to the European Quality of Life 5-Dimension (EQ-5D) Questionnaire only showed a significant benefit for early IFNB-1b treatment for year 3 (P =.016), both indicating no significant QoL impact of the IFNB-1b treatment over the first 2 years of CIS.

 As a further efficacy measure, Dr Hartung also indicated significant improvements at 3-years in the McDonald MS rating, again as a 46% risk reduction associated with early IFNB-1b treatment (HR, 0.54; log rank P <.0001). Finally, significant benefit of early IFNB-1b treatment was seen for both the annualised relapse rates (P =. 029) and the MS Functional Composite – Paced Auditory Serial Addition Test (MSFC – PASAT) score (P =.0106), although with the latter there were no significant differences in the MSFC 25-Foot Walk or 9-Hole Peg Test, as for the overall MSFC score.

 For the brain magnetic resonance imaging (MRI) 3-year outcomes, a significant effect was seen in favour of early IFNB-1b treatment on the development of new MRI activity (P <.0001), relating to new or enlarging T2 lesions or Gd-enhancing lesions, with a beneficial trend also seen as a more pronounced decrease in existing T2-lesion volume (P =.07).

 Dr Hartung also reported on their neutralising antibody analysis, although this was assessed only for the early treatment group due to the availability of samples. Here, the development of neutralising antibodies did not affect the time to CDMS and EDSS progression, or the annualised relapse rate.

 The incidence of adverse events (AEs) was well within the established range of AEs for IFNB-1b treatment and, according to the investigator assessment, the vast majority of the new serious AEs had no relation to study medication. There have also been no deaths during this study period.

 Finally, Dr Hartung again stressed, "This is the first study in CIS patients presenting with their first demyelinating event that was prospectively designed to examine the longer-term impact of early versus delayed treatment on disease progression." Furthermore, these findings support the value of early treatment with IFNB-1b following the very first clinical presentation of CIS.