Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group

ArticleinAnnals of Neurology 43(1):79-87 · February 1998with18 Reads
DOI: 10.1002/ana.410430114 · Source: PubMed
Abstract
The Multiple Sclerosis Collaborative Research Group trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon beta-1a (IFNbeta-1a; AVONEX) in relapsing forms of multiple sclerosis. Initial magnetic resonance imaging results have been published; this report provides additional results. Treatment with IFNbeta-1a, 30 microg once weekly by intramuscular injection, resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and IFNbeta-1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and IFNbeta-1a patients was 1,578 and -12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Except for a minimal correlation of 0.30 between relapse rate and the number of gadolinium-enhanced lesions, correlations between MR and clinical measures at baseline and throughout the study were in general poor. Once weekly intramuscular IFNbeta-1a appears to impede the development of multiple sclerosis lesions at an early stage and has a favorable impact on the long-term sequelae of these inflammatory events as indicated by the slowed accumulation of T2 lesions.
    • "Interferon-β1a (Avonex) was approved by the FDA in 1996 for the treatment of patients with relapsing form of MS, and similar to Rebif, it is made by Chinese hamster ovarian cells. The FDA approval of this medication followed the results obtained from a clinical trial which was designed by the Multiple Sclerosis Collaborative Research Group (MSCRG) [32–34]. During this phase 3, multicenter, double-blind, placebo-controlled clinical trial, 301 patients with RRMS were randomized to be treated with IFN-β1a (30 Mg intramuscularly once weekly) or placebo, for 24 months. "
    [Show abstract] [Hide abstract] ABSTRACT: With the introduction of interferon- β 1b in 1993 as the first FDA-approved treatment for multiple sclerosis, the era of treatment of this incurable disease began, and its natural course was permanently changed. Currently, seven different treatments for patients with multiple sclerosis with different mechanisms of action and dissimilar side effect profiles exist. These medications include interferon- β 1a intramuscular (Avonex), interferon- β 1a subcutaneous (Rebif), interferon- β 1b subcutaneous (Betaseron/Extavia), glatiramer acetate (Copaxone), natalizumab (Tysabri), fingolimod (Gilenya), teriflunomide (Aubagio), and mitoxantrone (Novantrone). In addition, a large number of clinical trials are being conducted to assess the safety and efficacy of various experimental agents in patients with multiple sclerosis, including alemtuzumab, dimethyl fumarate, laquinimod, rituximab, daclizumab, and cladribine. In this paper, the author presents a concise and comprehensive review of present and potential treatments for this incurable disease.
    Full-text · Article · Feb 2013
    • "Placebo-controlled clinical studies have shown that IM IFNβ-1a reduces T2 LV [31], slows disability progression, [32], and prevents development of brain atrophy [33–36]. However, despite these known effects of treatment with IM IFNβ-1a, both the early and late disease duration groups of MS patients exhibited loss of brain tissue and, in particular, developed cortical atrophy over the 2 years in the present study. "
    [Show abstract] [Hide abstract] ABSTRACT: We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR) multiple sclerosis (MS) and its association with lesion volume (LV) accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD) at baseline of ≤24 months were classified in the early group (DD of 1.2 years, n = 37), while patients with DD > 24 months were classified in the late group (DD of 7.1 years, n = 99). Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV) (P < 0.001), cortical volume (CV) (P < 0.001), and in T2-LV (P < 0.001) were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (P < 0.01). No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (P = 0.01). Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.
    Full-text · Article · Jan 2013
    • "Over the last decade, a number of immunomodulatory and immunosuppressive therapies have been approved for clinical use based primarily on demonstration of their ability to suppress focal inflammatory activity, i.e., lesion formation, and clinical relapses (Comi et al., 2001; Leary et al., 2003; Li and Paty, 1999; Li et al., 2001; Miller et al., 1999; Paty and Li, 1993; Simon et al., 1998; Simon et al., 2000; Zhao et al., 2000). Development of these therapies has been critically dependent on MRI because of the ability of MRI to visualize lesion formation with an order of magnitude greater sensitivity than clinical observation is able to detect relapses The number and volume of MS lesions represent the " burden of disease " and are predictive of patients' clinical course over the long term (O'Riordan et al., 1998). "
    [Show abstract] [Hide abstract] ABSTRACT: Magnetic resonance (MR) imaging is often used to characterize and quantify multiple sclerosis (MS) lesions in the brain and spinal cord. The number and volume of lesions have been used to evaluate MS disease burden, to track the progression of the disease and to evaluate the effect of new pharmaceuticals in clinical trials. Accurate identification of MS lesions in MR images is extremely difficult due to variability in lesion location, size and shape in addition to anatomical variability between subjects. Since manual segmentation requires expert knowledge, is time consuming and is subject to intra- and inter-expert variability, many methods have been proposed to automatically segment lesions. The objective of this study was to carry out a systematic review of the literature to evaluate the state of the art in automated multiple sclerosis lesion segmentation. From 1240hits found initially with PubMed and Google scholar, our selection criteria identified 80 papers that described an automatic lesion segmentation procedure applied to MS. Only 47 of these included quantitative validation with at least one realistic image. In this paper, we describe the complexity of lesion segmentation, classify the automatic MS lesion segmentation methods found, and review the validation methods applied in each of the papers reviewed. Although many segmentation solutions have been proposed, including some with promising results using MRI data obtained on small groups of patients, no single method is widely employed due to performance issues related to the high variability of MS lesion appearance and differences in image acquisition. The challenge remains to provide segmentation techniques that work in all cases regardless of the type of MS, duration of the disease, or MRI protocol, and this within a comprehensive, standardized validation framework. MS lesion segmentation remains an open problem.
    Full-text · Article · Sep 2012
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