Interferon beta-1-b in Secondary Progressive MS. Results from a 3-year controlled study. The North American Study Group on Interferon beta-1-b in Secondary Progressive MS

University of Vermont, College of Medicine, Burlington 05401, USA.
Neurology (Impact Factor: 8.29). 11/2004; 63(10):1788-95. DOI: 10.1212/01.WNL.0000146958.77317.3E
Source: PubMed


To evaluate the efficacy and safety of interferon beta-1b (IFNbeta-1b) in subjects with secondary progressive multiple sclerosis (SPMS).
This 3-year, multicenter, double-blind, placebo-controlled, randomized trial of IFNbeta-1b included 939 subjects from the United States and Canada with SPMS and Expanded Disability Status Scale (EDSS) scores ranging from 3.0 to 6.5. Subjects were randomly assigned to receive either placebo or IFNbeta-1b (250 microg or 160 microg/m2 body surface area), administered subcutaneously every other day. The primary outcome was time to progression by > or =1.0 EDSS point (0.5 point if EDSS score was 6.0 to 6.5 at entry) confirmed at 6 months. Secondary outcomes included mean change in EDSS score from baseline, relapse-related measures, MRI activity, and a standardized neuropsychological function test.
There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNbeta-1b treatment groups. However, IFNbeta-1b treatment resulted in improvement on secondary outcome measures involving clinical relapses, newly active MRI lesions, and accumulated burden of disease on T2-weighted MRI. Effects were similar for both IFNbeta-1b treatment groups. Neutralizing antibodies to IFNbeta-1b were detected in 23% of 250-microg and 32% of 160-microg/m2 recipients, but their presence did not consistently affect clinical or MRI outcomes. IFNbeta-1b was also well tolerated at both doses.
Although no treatment benefit was seen on the time to confirmed progression of disability, relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested, a result consistent with the outcomes of earlier clinical trials.

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    • "The primary endpoint in both studies was time to disability progression over 3 years. Although this was prolonged by more than 200 days in both studies among patients receiving IFN beta-1b compared with placebo, the difference was only significant in the European study (P < 0.001) [8, 36–39]. In both studies, compared with placebo, IFN beta-1b reduced ARR over 3 years and prolonged time to first relapse by more than 200 days (P ≤ 0.01, all comparisons) [8, 36]. "
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    ABSTRACT: Interferon (IFN) beta-1b was the first disease-modifying therapy to be approved for the treatment of multiple sclerosis (MS), and over 21 years of follow-up data demonstrate its efficacy and long-term safety profile. Following recent regulatory approvals in the USA and European Union, IFN beta-1b is now one of the seven disease-modifying therapies [intramuscular IFN beta-1a; subcutaneous (SC) IFN beta-1a; IFN beta-1b SC; glatiramer acetate SC; oral dimethyl fumarate; oral teriflunomide; and intravenous alemtuzumab] indicated for first-line use in relapsing–remitting MS. Here we review the clinical trial and follow-up data for IFN beta-1b and discuss factors that clinicians may consider when selecting this treatment, both at first line in early MS, and later in the disease course. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0149-1) contains supplementary material, which is available to authorized users.
    Preview · Article · Sep 2014 · Advances in Therapy
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    • "All target the CNS inflammation that results in demyelination and axonal damage, and are most effective when used in the earlier phases of the disease process [43] [44]. Treatment is less effective in secondary-progressive MS (SPMS) [45] [46] [47], when neurodegenerative processes become more important determinants of disability progression than inflammation. Second-generation therapies used to treat relapsing MS include natalizumab, administered by intravenous infusion, and the oral agents fingolimod and teriflunomide; none has been studied in SPMS. "
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    ABSTRACT: The Latin American MS Experts’ Forum has developed practical recommendations on the initiation and optimization of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis (RRMS). The recommendations reflect the unique epidemiology of MS and the clinical practice environment in Latin American countries. Treatment response may be evaluated according to changes in relapses; progression, as assessed by the Expanded Disability Status Scale and the Timed 25-foot Walk; and lesion number on magnetic resonance imaging. Follow-up assessments are recommended every six months, or annually for stable patients. Cognitive function should be evaluated in all RRMS patients at baseline and annually thereafter. These recommendations are intended to assist clinicians in Latin America in developing a rational approach to treatment selection and sequencing for their RRMS patients.
    Full-text · Article · Apr 2014 · Journal of the neurological sciences
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    • "The progressive phase of MS, either secondary or primary, reflects a poorly understood insidious widespread axonal degeneration that is age-related and independent of relapses [2-4]. Currently available disease-modifying treatments, which act by modifying the inflammatory response, reduce the frequency of relapses, but are not effective in progressive MS [5-7]. "
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    ABSTRACT: Currently available disease-modifying treatments acting by modifying the immune response are ineffective in progressive multiple sclerosis (MS), which is caused by a widespread axonal degeneration. Mechanisms suspected to be involved in this widespread axonal degeneration are reduced axonal energy metabolism, axonal glutamate toxicity, and reduced cerebral blood flow. Fluoxetine might theoretically reduce axonal degeneration in MS because it stimulates energy metabolism through enhancing glycogenolysis, stimulates the production of brain-derived neurotrophic factor, and dilates cerebral arterioles. The current document presents the protocol of a clinical trial to test the hypothesis that fluoxetine slows down the progressive phase of MS. The FLUOX-PMS trial is a multi-center, randomized, controlled and double-blind clinical study. A total of 120 patients with the diagnosis of either secondary or primary progressive MS will be treated either by fluoxetine (40 mg daily) or placebo for a total period of 108 weeks. The primary endpoint is the time to confirmed disease progression defined as either at least a 20% increase in the timed 25-Foot Walk or at least a 20% increase in the 9-Hole Peg Test. Secondary endpoints include the Hauser ambulation index, cognitive changes, fatigue, magnetic resonance imaging of the brain, and in a small subgroup optical coherence tomography. The FLUOX-PMS trial will gives us information as to whether fluoxetine has neuroprotective effects in patients with progressive MS.Trial Registration: Eudra-CT: 2011-003775-11.
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