Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis

Boster, Aaron; Ford, Corey C.; Neudorfer, Orit; Gilgun-Sherki, Yossi

doi:10.1586/14737175.2015.1040768

Cited by 36 publications

(23 citation statements)

References 88 publications

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“…Observational studies have shown interferon beta and glatiramer acetate are not associated with long term harm; patients can be reassured they are unlikely to experience serious side effects 343536…”

Section: What Are the Harms?mentioning

confidence: 99%

Disease-modifying therapies for multiple sclerosis

Angelis

John

Brownlee

2018

BMJ

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Section: What Are the Harms?mentioning

confidence: 99%

Disease-modifying therapies for multiple sclerosis

Angelis

John

Brownlee

2018

BMJ

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“…It has consistently demonstrated an annualized relapse rate (ARR) reduction of ~30% in Copaxone-treated patients compared to those treated with placebo in clinical trials. It continues to be an efficacious treatment for multiple sclerosis with a favorable safety profile demonstrated over 20 years of clinical use and over two million patient-years of exposure [15]. Studies have shown that a large proportion of Copaxone-treated patients (38 to 56%) demonstrate high response, based on varying response definitions [11].…”

Section: Introductionmentioning

confidence: 99%

A pharmacogenetic signature of high response to Copaxone in late-phase clinical-trial cohorts of multiple sclerosis

Ross

Towfic²,

Shankar³

et al. 2017

Genome Med

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BackgroundCopaxone is an efficacious and safe therapy that has demonstrated clinical benefit for over two decades in patients with relapsing forms of multiple sclerosis (MS). On an individual level, patients show variability in their response to Copaxone, with some achieving significantly higher response levels. The involvement of genes (e.g., HLA-DRB1*1501) with high inter-individual variability in Copaxone’s mechanism of action (MoA) suggests the potential contribution of genetics to treatment response. This study aimed to identify genetic variants associated with Copaxone response in patient cohorts from late-phase clinical trials.MethodsSingle nucleotide polymorphisms (SNPs) associated with high and low levels of response to Copaxone were identified using genome-wide SNP data in a discovery cohort of 580 patients from two phase III clinical trials of Copaxone. Multivariable Bayesian modeling on the resulting SNPs in an expanded discovery cohort with 1171 patients identified a multi-SNP signature of Copaxone response. This signature was examined in 941 Copaxone-treated MS patients from seven independent late-phase trials of Copaxone and assessed for specificity to Copaxone in 310 Avonex-treated and 311 placebo-treated patients, also from late-phase trials.ResultsA four-SNP signature consisting of rs80191572 (in UVRAG), rs28724893 (in HLA-DQB2), rs1789084 (in MBP), and rs139890339 (in ZAK(CDCA7)) was identified as significantly associated with Copaxone response. Copaxone-treated signature-positive patients had a greater reduction in annualized relapse rate (ARR) compared to signature-negative patients in both discovery and independent cohorts, an effect not observed in Avonex-treated patients. Additionally, signature-positive placebo-treated cohorts did not show a reduction in ARR, demonstrating the predictive as opposed to prognostic nature of the signature. A 10% subset of patients, delineated by the signature, showed marked improvements across multiple clinical parameters, including ARR, MRI measures, and higher proportion with no evidence of disease activity (NEDA).ConclusionsThis study is the largest pharmacogenetic study in MS reported to date. Gene regions underlying the four-SNP signature have been linked with pathways associated with either Copaxone’s MoA or the pathophysiology of MS. The pronounced association of the four-SNP signature with clinical improvements in a ~10% subset of the MS patient population demonstrates the complex interplay of immune mechanisms and the individualized nature of response to Copaxone.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0436-y) contains supplementary material, which is available to authorized users.

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“…In clinical trials, GA significantly reduced disease activity, as evidenced by fewer GdE lesions and lower annualized relapse rates (ARR) in patients with RRMS . GA is safe and well‐tolerated, and its effects on disability and relapse are sustained with continuous use . In patients presenting with clinically isolated syndrome and brain MRI lesions, early treatment with GA delayed both a second attack and conversion to clinically definite MS, and reduced MRI activity …”

Section: Introductionmentioning

confidence: 99%

Once‐daily glatiramer acetate decreases magnetic resonance imaging disease activity in Japanese patients with relapsing–remitting multiple sclerosis

Yamamura

Ashtamker

Ladkani

et al. 2017

Clinical & Exp Neuroim

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ObjectiveMultiple sclerosis (MS) prevalence, clinical patterns, and treatment responses vary between races and geographical latitudes. Glatiramer acetate (GA; Copaxone) has provided a safe, effective treatment option for relapsing–remitting MS patients in the USA, European nations, and other countries for decades. The objective of the present study was to assess the safety and efficacy of GA in reducing magnetic resonance imaging disease activity in Japanese patients with active relapsing–remitting MS.MethodsThis phase 2, multicenter, open‐label, single‐arm, 52‐week study measured the effect of GA 20 mg once‐daily on magnetic resonance imaging disease activity. GA efficacy was evaluated through week 36, and safety through week 52. The primary end‐point was change in the mean number of T1‐weighted gadolinium‐enhancing (GdE) lesions from pretreatment (weeks –8, –4 and baseline) to weeks 28, 32 and 36. Secondary end‐points included a change in mean number of new T2‐weighted lesions, GdE lesion and T2 lesion volumes, annualized relapse rate, and Expanded Disability Status Scale scores.ResultsGA therapy reduced the number of new GdE lesions by 65.66% (95% CI 33.19–82.35%). The number of new T2 lesions and GdE lesion volume were also reduced from pretreatment. The annualized relapse rate was reduced by 42% compared with the 1 year before treatment. Changes in T2 lesion volume and Expanded Disability Status Scale scores were favorable, but less pronounced. Most common adverse events were injection‐site reactions.ConclusionsThe present study confirmed the well‐established safety, tolerability and efficacy profile of GA in Japanese MS patients.

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Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis

Cited by 36 publications

References 88 publications

Disease-modifying therapies for multiple sclerosis

Disease-modifying therapies for multiple sclerosis

A pharmacogenetic signature of high response to Copaxone in late-phase clinical-trial cohorts of multiple sclerosis

Once‐daily glatiramer acetate decreases magnetic resonance imaging disease activity in Japanese patients with relapsing–remitting multiple sclerosis

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