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From University Hospital (L.K.), Basel, Switzerland; Vrije Universiteit Medical Centre (C.H.P., F.B.), Amsterdam, The Netherlands; The Ottawa Hospital (M.S.F.), Ottawa, Canada; Clinique Neurologique (G.E.), Rennes, France; Heinrich-Heine-Universität (H.P.H.), Düsseldorf, Germany; Institute of Neurology (D.H.M.), University College, London, UK; Hospitals Vall d’Hebron (X.M.), Barcelona, Spain; Schering AG (L.B., P.J., C.P., R.S.), Berlin, Germany; and University Hospital (Dr Pohl), Bonn, Germany.
Address correspondence and reprint requests to Professor Ludwig Kappos, Neurology, Outpatient Clinics Neurology–Neurosurgery and Department of Research, University Hospital, Petersgraben 4, 4031 Basel, Switzerland; e-mail: lkappos{at}uhbs.ch
Objective: To assess efficacy, safety, and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis (MS) (clinically isolated syndrome).
Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled trial. Patients with a first clinical demyelinating event and at least two clinically silent brain MRI lesions were randomized to interferon beta-1b (IFNB-1b) 250 µg subcutaneously (SC) every other day (EOD) (n = 292) or placebo (n = 176), until clinically definite MS (CDMS) was diagnosed or they had been followed for 24 months.
Results: After 2 years, 45% of placebo patients had converted to CDMS (Kaplan-Meier estimate; primary outcome measure) and 85% fulfilled the McDonald criteria (co-primary outcome measure). Overall interferon beta-1b delayed the time to diagnosis of CDMS (p < 0.0001) and McDonald MS (p < 0.00001). Hazard ratios (95% CI) were 0.50 (0.36 to 0.70) for CDMS and 0.54 (0.43 to 0.67) for McDonald MS favoring treatment with IFNB-1b. Treatment was well tolerated, as indicated by the low rate of patients dropping out of the study before CDMS was reached (6.6% overall, 7.2% in the IFNB-1b group).
Conclusions: Interferon beta-1b 250 µg subcutaneously every other day delayed conversion to clinically definite multiple sclerosis, and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis.
This article was previously published in electronic format as an Expedited E-Pub on August 16, 2006, at www.neurology.org.
*See the appendix for a list of BENEFIT Investigators.
Funded by Schering AG.
Disclosures: L. Kappos has received compensation for acting as principal investigator, member, or chair of planning and steering committees or advisory boards in clinical trials in multiple sclerosis and for lecturing at medical conferences sponsored by pharmaceutical companies. Payments for all mentioned activities have been exclusively used for funding of research at L.K.’s department. Research and the clinical operations (nursing and patient care services) of the Multiple Sclerosis Clinic and Research Centre at the University Hospital Basel, led by L.K., have also been supported by non-restricted grants from one or more pharmaceutical companies. The sponsoring pharmaceutical companies include Biogen Idec, GlaxoSmithKline, Novartis, Sanofi Aventis, Schering, Serono (all > US $10,000 per year); furthermore, Abbott, Bayer, Bayhill, Berlex, Boehringer Ingelheim, Bristol Myers, Centocor, Eisai, Elan, Genzyme, Neurocrine, Roche, Teva, UCB, Wyeth, and others. C Polman has received consulting fees from Biogen Idec, Schering, Teva, Serono, Novartis, Antisense and GlaxoSmithKline; lecture fees from Biogen Idec, Schering AG and Teva; and grant support from Biogen Idec, Novartis, Serono, Schering, Wyeth, and GlaxoSmithKline. M Freedman has received stipends from Transition Therapeutics and BioMS (both > $10,000 per year); honoraria from Bayer, Serono, Schering, Berlex, Teva, Pfizer; and a research grant from Serono. G Edan has received honoraria/consulting fees from Schering, Biogen Idec, Wyeth, Novartis, UCB Pharma, LFB; lecture fees from Schering, Biogen Idec; and grant support from Serono. H-P Hartung has received fees for speaking at scientific symposia and honoraria for consulting ad hoc from Bayer, Biogen Idec, Schering, Teva and Serono. D Miller has received honoraria/consulting fees from Biogen Idec, Wyeth, Novartis, UCB Pharma, and Bristol Meyers Squibb; lecture fees from Biogen Idec and Serono; and grant support from Biogen Idec, GlaxoSmithKline, and Schering. X Montalban has received honoraria/consulting fees from Biogen Idec, Wyeth, Novartis, and Bristol Myers Squibb; lecture fees from Biogen Idec, Serono and Schering; and grant support from Biogen Idec, Serono and Schering. F. Barkhof has served as a consultant to various pharmaceutical companies, including Aventis, Schering, and Serono. As the director of the Image Analysis Centre, he has been remunerated for time spent conducting the blind MRI analyses. L. Bauer, C. Pohl, and R. Sandbrink are salaried employees of Schering. P. Jakobs was a salaried employee of Schering and owns shares in Schering.
Received March 24, 2006. Accepted in final form June 28, 2006.
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