Efficacy of intramuscular interferon beta-1a in patients with clinically isolated syndrome: Analysis of subgroups based on new risk criteria
ABSTRACT Approximately 85% of multiple sclerosis (MS) cases begin as clinically isolated syndromes (CIS). Results from the Controlled High-Risk Subjects Avonex((R)) Multiple Sclerosis Prevention Study (CHAMPS) demonstrated that, in patients with CIS, treatment with intramuscular (IM) interferon beta-1a (IFNbeta-1a) 30 mug once weekly delayed conversion to clinically definite MS (CDMS) in the total population and in subgroups based on presenting syndromes and baseline magnetic resonance imaging (MRI) characteristics. Changes to clinical and MRI risk classification of presenting symptoms in recent studies prompted reanalysis of CHAMPS data. Presenting syndromes were assessed using a derived algorithm that stratifies patients into mono- or multifocal categories based on functional system scores. The ability of IM IFNbeta-1a to delay progression to CDMS in subgroups based on clinical presentation and MRI characteristics was assessed. Reanalysis of CHAMPS patients showed that 30% could be classified by clinical criteria as having multifocal disease at baseline. IM IFNbeta-1a initiated at a first demyelinating attack delayed CDMS in monofocal patients (P = 0.0013), patients with or without gadolinium-enhancing lesions (P = 0.0007, P = 0.0405) and patients with at least nine T2 lesions at baseline (P = 0.0044). These data confirm that IM IFNbeta-1a delays conversion to CDMS in patients with CIS.
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- "Post hoc analysis found that some patients were multifocal. M.S. Freedman et al. 150 presentation were eligible, although a post hoc analysis discovered evidence that 30% of patients had multifocal findings at baseline (O′Connor et al., 2009). ETOMS grouped patients as being monosymptomatic or polysymptomatic, but these terms cannot be equated to monofocal or multifocal presentation. "
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. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.03/2014; 3(2):147–155. DOI:10.1016/j.msard.2013.07.001
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ABSTRACT: The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment reduced the risk of CDMS by 37% (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed treatment. The risk for confirmed disability progression was not significantly lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median FAMS-TOI scores were 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b, although a delay in treatment by up to 2 years did not affect long-term disability outcomes. Bayer Schering Pharma.The Lancet Neurology 09/2009; 8(11):987-97. DOI:10.1016/S1474-4422(09)70237-6 · 21.82 Impact Factor
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ABSTRACT: More than half of patients with a clinically isolated syndrome (CIS) develop clinically definite mul-tiple sclerosis (CDMS). Patients at high risk for CDMS often present with asymptomatic lesions characteristic of CDMS on magnetic resonance imaging scans, although an absence of asymptomatic lesions is not atypical. Phase 3 studies of interferon beta in patients with a CIS suggest that this treat-ment can delay conversion to CDMS and reduce the risk of new asymptomatic white matter lesions. We reviewed phase 3 studies (CHAMPS, BENEFIT, and ETOMS) and post hoc analyses assessing the efficacy of interferon beta in delaying CDMS in patients with a CIS. The evidence supports early ini-tiation of treatment. Int J MS Care. 2010;12:42–50.04/2010; 12(1). DOI:10.7224/1537-2073-12.1.42