Efficacy of Disease-Modifying Therapies in Relapsing Remitting Multiple Sclerosis: A Systematic Comparison

ArticleinEuropean Neurology 60(1):1-11 · February 2008with5 Reads
DOI: 10.1159/000127972 · Source: PubMed
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 characteristics, such that cross-comparisons of relative risk reductions 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, Betaseron, Copaxone, Rebif and Tysabri in patients with RRMS were identified for analysis. Only randomized, placebo-controlled, double-blind studies were included. The clinical efficacy 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 proportion of patients free of gadolinium-enhancing lesions at 1 year or 9 months. Based on these analyses, Betaseron, Rebif, and Tysabri show comparable effects, whereas for several endpoints Avonex or Copaxone did not significantly differ 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.
    • "There is no cure for MS and all available treatments attempt to reduce the number of relapses, recover function following relapse, and reduce disability progression (Compston and Coles, 2002). Among different available disease-modifying treatments such as mitoxantrone , natalizumab, fingolimod, glatiramer acetate, dimethyl fumarate, and teriflunomide (Comi, 2009; Freedman et al., 2008; Giovannoni, 2004; Goodin et al., 2002; Goodin, 2008; He et al., 2012; Manouchehrinia and Constantinescu, 2012; Qizilbash et al., 2012; Stuve et al., 2008) IFNβ, approved in 1993 as a therapeutic protein, is a common first-line treatment for relapsing-remitting MS (McKeage, 2008; McCormack and Scott, 2004a; Tsang and Macdonell, 2011; Vosoughi and Freedman, 2010) and in some cases for secondary-progressive MS (Paolicelli et al., 2009). IFNβ has been produced in Escherichia coli (Knobler et al., 1993) and as well in Chinese Hamster Ovary (CHO) cells (SPECTRIMS study group, 2001). "
    [Show abstract] [Hide abstract] ABSTRACT: Interferon beta (IFNβ) is a cytokine that is naturally produced by the immune system in response to biological and chemical stimuli. It signals by binding to the heterodimeric type I IFN receptor composed of the IFNAR1 and IFNAR2 chains, and regulates the expression of a plethora of genes by means of the classical JAK/STAT and other pathways. IFNβ is pleiotropic in that it elicits antiviral, antiproliferative, and immunomodulatory activities on numerous cell types. The biological activities underpin the mechanisms by which the protein is used to treat various diseases such as hepatitis C infection and multiple sclerosis. Despite the success of IFNβ therapy, the drug may evoke the production of antidrug antibodies that may reduce treatment efficiency. Immunogenicity is related to many factors: among them, structural properties, particularly aggregation, and T-cell and B-cell epitopes in the structure of IFNβ, appear to be important. Knowledge of the structural properties of IFNβ and its relation to immunogenicity may help scientists to develop safer and more effective forms. Several methods have been used to predict and reduce the immunogenicity of certain IFNβ drug products. In this chapter, we review the current knowledge on IFNβ from its structure, dynamic conformation, signaling pathway, and mechanism of action to its therapeutic effects. Immunogenicity and its relation to structural properties of IFNβ are also discussed.
    Full-text · Chapter · Jan 2016 · Journal of Neuroimmunology
    • "Various disease-modifying drugs, including IFNβ-1a and IFNβ-1b, glatiramer acetate (GA), natalizumab, mitoxantrone, and fingolimod that are licensed worldwide to reduce the frequency of clinical attacks with the expectation of slowing disability progression [14]. Great majority of studies related to IFNs have been directed towards to determination of their effects on diseases and biological structures [9, 39]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Interferon Beta (IFNβ) was the first proven drug for the treatment of Multiple Sclerosis (MS). The diagnosis of MS frequently occurs in women at childbearing age (especially in twenties and thirties). Therefore, the pregnancy process is major concern for many women with MS. Data on women exposed to IFNβ during pregnancy are limited. The aim of our study was to investigate the teratogenic potential of IFNβ on embryonic development via embryo culture technique. Recently, this technique has been often used for determined teratogenic effect of pharmacologic drugs and potential teratogens on embryonic development. Materials and methods: In this study, IFNβ was applied to the culture medium and after 48 hours' culture period, effects of IFNβ's (1000 IU/IFNβ-1a and 1000 IU/IFNβ-1b) on embryonic development were morphologically investigated. Results: According to morphologic scoring system, total morphologic score, somite number and protein contents were similar between control group and two experimental groups (p>0.05). On the other hand; yolk sac diameter, crown rump length and head length were significantly decreased in two experimental groups compared to control group (p<0.05). Conclusions: Consequently, IFNβ-1a and IFNβ-1b, applied to the culture medium, have no macroscopic teratogenic effect on embryonic development. However, in respect of morphometric measurements, IFNβ-1a and IFNβ-1b have caused growth retardation in embryo. This research related to interferon was the first study using vitro embryo culture technique, thus in our point of view, future studies which will be performed by using different doses of IFN will contribute to the literature.
    Full-text · Article · Dec 2015
    • "IFN-β or glatiramer acetate) (James et al., 2013; Pozuelo-Moyano et al., 2013). IFN-β treatment has proven effects on MRI activity in RRMS (Filippini et al., 2003; Freedman et al., 2008 ), thus our finding of a reduction of MRI activity upon IFN-β introduction was expected. The trend for a negative relationship between increasing 25(OH)D levels and MRI activity in the period without IFN-β was in line with our previous published data (Løken-Amsrud et al., 2012 ), as were the observed alterations of serum inflammation marker levels after initiation of therapy (Holmøy et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: To explore if vitamin D modulates interferon-β1a treatment effects in relapsing-remitting multiple sclerosis, we examined relationships between serum vitamin D and magnetic resonance imaging (MRI) activity and ten systemic inflammation markers in 88 patients, before and during treatment. Odds ratios for all MRI parameters were negatively associated with vitamin D levels before therapy, but converged to equally low values irrespective of vitamin D status during treatment. During therapy, similar alterations of MRI activity and inflammation markers were found across patients categorized by mean vitamin D values. This suggests that vitamin D status has no major influence on interferon-β1a treatment effects. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015
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