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Diego Cadavid - One of the best experts on this subject based on the ideXlab platform.
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efficacy of treatment of ms with ifnβ 1b or Glatiramer Acetate by monthly brain mri in the become study
Neurology, 2009Co-Authors: Diego Cadavid, Leo J Wolansky, Joan Skurnick, John A Lincoln, Jojy Cheriyan, K Szczepanowski, Stephen KaminAbstract:Background: There are no published MRI studies comparing interferon beta 1b (IFNβ-1b) and Glatiramer Acetate (GA) for treatment of relapsing multiple sclerosis (MS). Objective: To compare the efficacy of IFNβ-1b and GA for suppression of MS disease activity as evidenced on frequent brain MRI. Methods: A total of 75 patients with relapsing-remitting MS or clinically isolated syndromes were randomized to standard doses of IFNβ-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement. The primary outcome was the number of combined active lesions (CAL) per patient per scan during the first year, which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery (FLAIR) lesions. Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years. Results: Baseline characteristics were similar between the groups. The primary outcome showed similar median (75th percentile) CAL per patient per scan for months 1–12, 0.63 (2.76) for IFNβ-1b, and 0.58 (2.45) for GA (p = 0.58). There were no differences in new lesion or clinical relapses for 2 years. Only 4.4% of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions. Conclusion: Patients with relapsing multiple sclerosis randomized to interferon beta 1b or Glatiramer Acetate showed similar MRI and clinical activity.
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efficacy of treatment of ms with ifnbeta 1b or Glatiramer Acetate by monthly brain mri in the become study
Neurology, 2009Co-Authors: Diego Cadavid, Leo J Wolansky, Joan Skurnick, John A Lincoln, Jojy Cheriyan, K Szczepanowski, Stephen KaminAbstract:Background: There are no published MRI studies comparing interferon beta 1b (IFNβ-1b) and Glatiramer Acetate (GA) for treatment of relapsing multiple sclerosis (MS). Objective: To compare the efficacy of IFNβ-1b and GA for suppression of MS disease activity as evidenced on frequent brain MRI. Methods: A total of 75 patients with relapsing-remitting MS or clinically isolated syndromes were randomized to standard doses of IFNβ-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement. The primary outcome was the number of combined active lesions (CAL) per patient per scan during the first year, which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery (FLAIR) lesions. Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years. Results: Baseline characteristics were similar between the groups. The primary outcome showed similar median (75th percentile) CAL per patient per scan for months 1–12, 0.63 (2.76) for IFNβ-1b, and 0.58 (2.45) for GA (p = 0.58). There were no differences in new lesion or clinical relapses for 2 years. Only 4.4% of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions. Conclusion: Patients with relapsing multiple sclerosis randomized to interferon beta 1b or Glatiramer Acetate showed similar MRI and clinical activity.
Stephen Kamin - One of the best experts on this subject based on the ideXlab platform.
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efficacy of treatment of ms with ifnβ 1b or Glatiramer Acetate by monthly brain mri in the become study
Neurology, 2009Co-Authors: Diego Cadavid, Leo J Wolansky, Joan Skurnick, John A Lincoln, Jojy Cheriyan, K Szczepanowski, Stephen KaminAbstract:Background: There are no published MRI studies comparing interferon beta 1b (IFNβ-1b) and Glatiramer Acetate (GA) for treatment of relapsing multiple sclerosis (MS). Objective: To compare the efficacy of IFNβ-1b and GA for suppression of MS disease activity as evidenced on frequent brain MRI. Methods: A total of 75 patients with relapsing-remitting MS or clinically isolated syndromes were randomized to standard doses of IFNβ-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement. The primary outcome was the number of combined active lesions (CAL) per patient per scan during the first year, which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery (FLAIR) lesions. Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years. Results: Baseline characteristics were similar between the groups. The primary outcome showed similar median (75th percentile) CAL per patient per scan for months 1–12, 0.63 (2.76) for IFNβ-1b, and 0.58 (2.45) for GA (p = 0.58). There were no differences in new lesion or clinical relapses for 2 years. Only 4.4% of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions. Conclusion: Patients with relapsing multiple sclerosis randomized to interferon beta 1b or Glatiramer Acetate showed similar MRI and clinical activity.
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efficacy of treatment of ms with ifnbeta 1b or Glatiramer Acetate by monthly brain mri in the become study
Neurology, 2009Co-Authors: Diego Cadavid, Leo J Wolansky, Joan Skurnick, John A Lincoln, Jojy Cheriyan, K Szczepanowski, Stephen KaminAbstract:Background: There are no published MRI studies comparing interferon beta 1b (IFNβ-1b) and Glatiramer Acetate (GA) for treatment of relapsing multiple sclerosis (MS). Objective: To compare the efficacy of IFNβ-1b and GA for suppression of MS disease activity as evidenced on frequent brain MRI. Methods: A total of 75 patients with relapsing-remitting MS or clinically isolated syndromes were randomized to standard doses of IFNβ-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement. The primary outcome was the number of combined active lesions (CAL) per patient per scan during the first year, which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery (FLAIR) lesions. Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years. Results: Baseline characteristics were similar between the groups. The primary outcome showed similar median (75th percentile) CAL per patient per scan for months 1–12, 0.63 (2.76) for IFNβ-1b, and 0.58 (2.45) for GA (p = 0.58). There were no differences in new lesion or clinical relapses for 2 years. Only 4.4% of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions. Conclusion: Patients with relapsing multiple sclerosis randomized to interferon beta 1b or Glatiramer Acetate showed similar MRI and clinical activity.
Fred D. Lublin - One of the best experts on this subject based on the ideXlab platform.
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treatment response score to Glatiramer Acetate or interferon beta 1a
Neurology, 2020Co-Authors: Francesca Bovis, Eva Havrdova, Fred D. Lublin, Maria Trojano, Tomas Kalincik, Gary Cutter, Charles B Malpas, Dana Horakova, Alexandre Prat, Marc GirardAbstract:Objective To compare the effectiveness of Glatiramer Acetate (GA) vs intra-muscular Interferon beta-1a (IFNbeta-1a)), we applied a previously published statistical method, aimed at identifying patients9 profiles associated with efficacy of treatments. Methods Data from 2 independent multiple sclerosis datasets, a randomized study (the CombiRx trial, evaluating GA vs IFNbeta-1a and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors. Results The overall ARR ratio of GA vs IFNbeta-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration and EDSS) detected differential response of GA vs IFNbeta-1a: in the trial, patients with the largest benefit from GA vs IFNbeta-1a (lower score quartile) had an ARR ratio of 0.40 (95%confidence interval [CI] = 0.25–0.63), those in the 2 middle quartiles of 0.90 (95% CI = 0.61–1.34) and those in the upper quartile of 1.14 (95%CI = 0.59–2.18) (heterogeneity p = 0.012); this result was validated on MSbase, with the corresponding ARR ratios of 0.58 (95% CI = 0.46–0.72), 0.92 (95% CI = 0.77–1.09) and 1.29 (95% CI = 0.97–1.71); heterogeneity p Conclusions We demonstrate the possibility of a criterion, based on patients9 characteristics, to choose whether to treat with GA or IFNbeta-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.
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treatment response score to Glatiramer Acetate or interferon beta 1a
Neurology, 2020Co-Authors: Francesca Bovis, Eva Havrdova, Fred D. Lublin, Maria Trojano, Tomas Kalincik, Gary Cutter, Charles B Malpas, Dana Horakova, Alexandre Prat, Marc GirardAbstract:OBJECTIVE: To compare the effectiveness of Glatiramer Acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments. METHODS: Data from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-1a) and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors. RESULTS: The overall ARR ratio of GA to IFN-β-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration, and Expanded Disability Status Scale score) detected differential response of GA vs IFN-β-1a: in the trial, patients with the largest benefit from GA vs IFN-β-1a (lower score quartile) had an ARR ratio of 0.40 (95% confidence interval [CI] 0.25-0.63), those in the 2 middle quartiles of 0.90 (95% CI 0.61-1.34), and those in the upper quartile of 1.14 (95% CI 0.59-2.18) (heterogeneity p = 0.012); this result was validated on MSBase, with the corresponding ARR ratios of 0.58 (95% CI 0.46-0.72), 0.92 (95% CI 0.77-1.09,) and 1.29 (95% CI 0.97-1.71); heterogeneity p < 0.0001). CONCLUSIONS: We demonstrate the possibility of a criterion, based on patients' characteristics, to choose whether to treat with GA or IFN-β-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.
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randomized study combining interferon and Glatiramer Acetate in multiple sclerosis
Annals of Neurology, 2013Co-Authors: Fred D. Lublin, Gary Cutter, Stacey S Cofield, Robin Conwit, Ponnada A Narayana, Flavia Nelson, Amber Salter, Tarah Gustafson, Jerry S. WolinskyAbstract:Objective A double-blind, randomized, controlled study to determine if combined use of interferon beta-1a (IFN) 30ug IM weekly and Glatiramer Acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis (RRMS).
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randomized study combining interferon and Glatiramer Acetate in multiple sclerosis
Annals of Neurology, 2013Co-Authors: Fred D. Lublin, Gary Cutter, Stacey S Cofield, Robin Conwit, Ponnada A Narayana, Flavia Nelson, Amber Salter, Tarah Gustafson, Jerry S. WolinskyAbstract:Objective A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30μg intramuscularly weekly and Glatiramer Acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing–remitting multiple sclerosis. Methods A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Results Combination IFN + GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Interpretation Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. ANN NEUROL 2013;73:327–340
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Interferon Beta and Glatiramer Acetate Therapy
Neurotherapeutics, 2013Co-Authors: Corey A. Mcgraw, Fred D. LublinAbstract:Interferon beta and Glatiramer Acetate have been mainstays of treatment in relapsingremitting multiple sclerosis for two decades. Remarkable advances in our understanding of immune function and dysfunction as well as increasingly sophisticated clinical trial design have stemmed from efforts to better understand these drugs. In this chapter, we review the history of their development and elaborate on known and theorized mechanisms of action. We describe the pivotal clinical trials that have led to their widespread use. We evaluate the clinical use of the drugs including tolerability, side effects, and efficacy measures. Finally, we look to the future of interferon beta and Glatiramer Acetate in the context of an ever growing armamentarium of treatments for relapsing remitting multiple sclerosis.
Jerry S. Wolinsky - One of the best experts on this subject based on the ideXlab platform.
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randomized study combining interferon and Glatiramer Acetate in multiple sclerosis
Annals of Neurology, 2013Co-Authors: Fred D. Lublin, Gary Cutter, Stacey S Cofield, Robin Conwit, Ponnada A Narayana, Flavia Nelson, Amber Salter, Tarah Gustafson, Jerry S. WolinskyAbstract:Objective A double-blind, randomized, controlled study to determine if combined use of interferon beta-1a (IFN) 30ug IM weekly and Glatiramer Acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis (RRMS).
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randomized study combining interferon and Glatiramer Acetate in multiple sclerosis
Annals of Neurology, 2013Co-Authors: Fred D. Lublin, Gary Cutter, Stacey S Cofield, Robin Conwit, Ponnada A Narayana, Flavia Nelson, Amber Salter, Tarah Gustafson, Jerry S. WolinskyAbstract:Objective A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30μg intramuscularly weekly and Glatiramer Acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing–remitting multiple sclerosis. Methods A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Results Combination IFN + GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Interpretation Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. ANN NEUROL 2013;73:327–340
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the combirx trial of combined therapy with interferon and Glatiramer Acetate in relapsing remitting ms design and baseline characteristics
Multiple sclerosis and related disorders, 2012Co-Authors: J W Lindsey, Jerry S. Wolinsky, Gary Cutter, Stacey S Cofield, Robin Conwit, Flavia Nelson, Tarah Gustafson, Thomas F Scott, Sharon G Lynch, Fred D. LublinAbstract:Background Interferon-β1a (IFNB) and Glatiramer Acetate (GA) are distinct therapies which are both partially effective for relapsing MS. It is not known if combining the two treatments would be more effective.
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neurologic consequence of delaying Glatiramer Acetate therapy for multiple sclerosis 8 year data
Acta Neurologica Scandinavica, 2005Co-Authors: Kenneth P Johnson, Corey C Ford, R P Lisak, Jerry S. WolinskyAbstract:Objective – To assess the long-term effectiveness of continuous Glatiramer Acetate (GA) therapy in relapsing-remitting multiple sclerosis (RRMS). Methods – This open-label extension followed a randomized, placebo-controlled, double-blind study of GA of approximately 30 months duration. Patients originally randomized to GA continued on it (group A) and those randomized to placebo switched to GA (group B). Results – Of 251 original patients, 142 (56.6%) remained in the study after 8 years. Annual relapse rate for both groups declined to approximately 0.2 (approximately one relapse every 5 years). However, a significantly larger proportion of patients in group A had stable or improved Expanded Disability Status Scale scores compared with group B (65.3% vs 50.4%, respectively; P = 0.0263), possibly attributable to the delay of GA treatment for approximately 30 months in group B. GA was well tolerated and no drug-related laboratory changes were observed. Conclusions – These data support early initiation of GA therapy as an efficacious and well-tolerated long-term treatment for RRMS patients.
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Glatiramer Acetate reduces the proportion of new ms lesions evolving into black holes
Neurology, 2001Co-Authors: Massimo Filippi, Jerry S. Wolinsky, Maria Pia Sormani, Marco Rovaris, Maria A Rocca, G ComiAbstract:The authors evaluated whether Glatiramer Acetate (GA) modifies the severity of tissue damage in 1,722 new lesions from 239 patients with MS enrolled in a placebo-controlled trial monitored with monthly cerebral MRI. The percentage of new lesions that evolved into "black holes" was lower in GA-treated than in placebo patients on scans at 7 (18.9 and 26.3%; p = 0.04) and 8 (15.6 and 31.4%; p = 0.002) months after lesion appearance. GA has a favorable effect on tissue disruption in MS lesions once they are formed.
Rina Aharoni - One of the best experts on this subject based on the ideXlab platform.
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The mechanism of action of Glatiramer Acetate in multiple sclerosis and beyond.
Autoimmunity reviews, 2012Co-Authors: Rina AharoniAbstract:In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), the immune system reacts again self myelin constitutes in the central nervous system (CNS), initiating a detrimental inflammatory cascade that leads to demyelination as well as axonal and neuronal pathology. The amino acid copolymer Glatiramer Acetate (GA, Copaxone) is an approved first-line treatment for MS that has a unique mode of action. Accumulated evidence from EAE-induced animals and from MS patients indicates that GA affects various levels of the innate and the adaptive immune response, generating deviation from the pro-inflammatory to the anti-inflammatory pathway. This review aims to provide a comprehensive perspective on the diverse mechanism of action of GA in EAE/MS, in particular on the in situ immunomodulatory effect of GA and its ability to generate neuroprotective repair consequences in the CNS. In view of its immunomodulatory activity, the beneficial effect of GA in various models of other autoimmune related pathologies, such as immune rejection and inflammatory bowel disease (IBD) is noteworthy.
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demyelination arrest and remyelination induced by Glatiramer Acetate treatment of experimental autoimmune encephalomyelitis
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Rina Aharoni, Avia Herschkovitz, Raya Eilam, Michal Blumberghazan, Michael Sela, Wolfgang Bruck, Ruth ArnonAbstract:The interplay between demyelination and remyelination is critical in the progress of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). In the present study, we explored the capacity of Glatiramer Acetate (GA, Copaxone) to affect the demyelination process and/or lead to remyelination in mice inflicted by chronic EAE, using both scanning electron microscopy and immunohistological methods. Spinal cords of untreated EAE mice revealed substantial demyelination accompanied by tissue destruction and axonal loss. In contrast, in spinal cords of GA-treated mice, in which treatment started concomitantly with disease induction (prevention), no pathology was observed. Moreover, when treatment was initiated after the appearance of clinical symptoms (suppression) or even in the chronic disease phase (delayed suppression) when substantial demyelination was already manifested, it resulted in a significant decrease in the pathological damage. Detection of oligodendrocyte progenitor cells (OPCs) expressing the NG2 or O4 markers via colocalization with the proliferation marker BrdU indicated their elevated levels in spinal cords of GA-treated mice. The mode of action of GA in this system is attributed to increased proliferation, differentiation, and survival of OPCs along the oligodendroglial maturation cascade and their recruitment into injury sites, thus enhancing repair processes in situ.
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demyelination arrest and remyelination induced by Glatiramer Acetate treatment of experimental autoimmune encephalomyelitis
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Rina Aharoni, Avia Herschkovitz, Raya Eilam, Michal Blumberghazan, Michael Sela, Wolfgang Bruck, Ruth ArnonAbstract:The interplay between demyelination and remyelination is critical in the progress of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). In the present study, we explored the capacity of Glatiramer Acetate (GA, Copaxone) to affect the demyelination process and/or lead to remyelination in mice inflicted by chronic EAE, using both scanning electron microscopy and immunohistological methods. Spinal cords of untreated EAE mice revealed substantial demyelination accompanied by tissue destruction and axonal loss. In contrast, in spinal cords of GA-treated mice, in which treatment started concomitantly with disease induction (prevention), no pathology was observed. Moreover, when treatment was initiated after the appearance of clinical symptoms (suppression) or even in the chronic disease phase (delayed suppression) when substantial demyelination was already manifested, it resulted in a significant decrease in the pathological damage. Detection of oligodendrocyte progenitor cells (OPCs) expressing the NG2 or O4 markers via colocalization with the proliferation marker BrdU indicated their elevated levels in spinal cords of GA-treated mice. The mode of action of GA in this system is attributed to increased proliferation, differentiation, and survival of OPCs along the oligodendroglial maturation cascade and their recruitment into injury sites, thus enhancing repair processes in situ.