Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review Eur Neurol 2008;60:1–11 DOI: 10.1159/000127972 Efficacy of Disease-Modifying Therapies in Relapsing Remitting Multiple Sclerosis: A Systematic Comparison Mark S. Freedman a Bruce Hughes b Daniel D. Mikol c Randy Bennett d Brian Cuffel e Vamil Divan e Nicole LaVallee f Ahmad AL-Sabbagh d a Department of Medicine (Neurology), University of Ottawa, Ottawa, Ont., Canada; b Ruan Neurology Clinic and Research Center, Des Moines, Iowa, c Department of Neurology, University of Michigan, Ann Arbor, Mich., d EMD Serono, Inc., Rockland, Mass., e Pfizer Inc., New York, N.Y., and f PROMETRIKA LLC, Cambridge, Mass., USA eral endpoints Avonex or Copaxone did not significantly dif- fer from placebo. In the absence of head-to-head studies for all products used to treat RRMS, it still may be possible to compare treatment effects by applying evidence-based medicine principles. Copyright © 2008 S. Karger AG, Basel Introduction The treatment of relapsing-remitting multiple sclero- sis (RRMS) has changed substantially with the advent of effective disease-modifying therapies (DMTs) that can alter the natural history of disease. DMTs have demon- strated the ability to reduce the incidence of relapses and the MRI activity thought to be linked to the underlying perceived inflammatory phase of the disease. They also retard disease progression, as assessed clinically by changes in a neurological rating scale called the Expand- ed Disability Status Scale (EDSS). There are currently 6 Food and Drug Administration (FDA)-approved treat- ments for RRMS in the United States. In 1993, the first DMT, interferon beta (IFN  )-1b (Betaseron ), was ap- proved for RRMS to reduce the rate and severity of re- lapses. This was followed by approval of IFN -1a (Avon- ex ) in 1996 and glatiramer acetate (Copaxone ) in 1997. Key Words Disease-modifying therapy  Evidence-based medicine  Interferon beta  Glatiramer  Natalizumab  Therapeutic gain Abstract The treatment of relapsing-remitting multiple sclerosis (RRMS) has become more effective over the last decade with the advent of the currently available disease-modifying therapies (DMTs). Pivotal clinical studies differ in many char- acteristics, such that cross-comparisons of relative risk re- ductions are of limited value and can be misleading. Our objective was to compare the clinical efficacy of currently approved first-line DMTs in patients with RRMS, applying an evidence-based medicine approach. We reviewed all phase III pivotal trials of DMTs. Six clinical trials of Avonex , Betase- ron , Copaxone , Rebif  and Tysabri  in patients with RRMS were identified for analysis. Only randomized, placebo-con- trolled, double-blind studies were included. The clinical ef- ficacy endpoints compared were: proportion of relapse-free patients at 1 and 2 years; annualized relapse rate at 2 years; proportion of progression-free patients at 2 years, and pro- portion of patients free of gadolinium-enhancing lesions at 1 year or 9 months. Based on these analyses, Betaseron, Re- bif, and Tysabri show comparable effects, whereas for sev- Received: July 25, 2007 Accepted: November 13, 2007 Published online: April 25, 2008 Dr. Mark Steven Freedman, Professor of Medicine (Neurology) University of Ottawa, The Ottawa Hospital-General Campus 501 Smyth Road Ottawa, Ont. K1H 8L6 (Canada) Tel. +1 613 737 8917, Fax +1 613 737 8857, E-Mail mfreedman@ottawahospital.on.ca © 2008 S. Karger AG, Basel 0014–3022/08/0601–0001$24.50/0 Accessible online at: www.karger.com/ene