title: Moving toward earlier treatment of multiple sclerosis: Findings from a decade of clinical trials and implications for clinical practice.
abstract: The first clinical presentation of multiple sclerosis (MS) is usually a single episode of typical symptoms and signs and is designated a "first clinical demyelinating event" (FCDE) or a "clinically isolated syndrome". Patients with an FCDE who show 'silent' magnetic resonance imaging lesions are at high risk of further clinical events and therefore of meeting the criteria for the diagnosis of clinically definite MS (CDMS). Here we review five Phase III trials, in which treatment with the following disease-modifying drugs (DMDs) was initiated at this early stage: interferon beta (ETOMS, CHAMPS, BENEFIT, and REFLEX) and glatiramer acetate (PreCISe). Differences in the design of the trials and their patient inclusion criteria limit comparisons. However, the proportion of placebo-treated patients who developed CDMS within 2 years was 38-45% across studies, and this rate was significantly reduced by DMD treatment. Conversion to McDonald MS was reported by only two of the trials: BENEFIT (2001 criteria) and REFLEX (2005 criteria). Around 85% of placebo-treated patients developed McDonald MS by 2 years in each, and again a beneficial effect of DMD treatment was seen. Overall, these studies support early use of DMDs to treat patients with an FCDE who are at high risk of conversion to CDMS.
authors: Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada. Electronic address: mfreedman@toh.on.ca.
authors: Mark S
authors: MS
authors: Freedman
authors: Department of Neurology and Institute of Experimental Neurology, Università Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
authors: Giancarlo
authors: G
authors: Comi
authors: Department of Neurology, Neurosurgery & Behavioral Sciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy.
authors: Nicola
authors: N
authors: De Stefano
authors: VU University Medical Center, Postbus 7057, 1007 MB Amsterdam, The Netherlands.
authors: Frederik
authors: F
authors: Barkhof
authors: VU University Medical Center, Postbus 7057, 1007 MB Amsterdam, The Netherlands.
authors: Chris H
authors: CH
authors: Polman
authors: VU University Medical Center, Postbus 7057, 1007 MB Amsterdam, The Netherlands.
authors: Bernard M J
authors: BM
authors: Uitdehaag
authors: Global Clinical Development Unit, Merck Serono S.A., 9 Chemin des Mines, 1202 Geneva, Switzerland.
authors: Lorenz
authors: L
authors: Lehr
authors: Global Clinical Development Unit, Merck Serono S.A., 9 Chemin des Mines, 1202 Geneva, Switzerland.
authors: Bettina
authors: B
authors: Stubinski
authors: Departments of Neurology and Biomedicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
authors: Ludwig
authors: L
authors: Kappos
keywords: Clinically isolated syndrome; Disease-modifying drug; First clinical demyelinating event; Glatiramer acetate; Interferon beta; Multiple sclerosis