Long-term safety and tolerability of glatiramer acetate 20 mg in the treatment of relapsing forms of multiple sclerosis

Ziemssen, Tjalf; Ashtamker, Natalia; Rubinchick, Svetlana; Knappertz, Volker; Comi, Giancarlo

doi:10.1080/14740338.2017.1274728

Cited by 21 publications

(33 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar findings of relatively stable disease (75% of patients without EDSS worsening) have also been reported from a retrospective Spanish cohort of patients treated with GA for at least 5 years [12]. The adverse drug reactions documented over the course of the study were not unexpected for GA [10, 13], corresponding principally to local injection site reactions or systemic immediate post-injection reactions.…”

Section: Discussionsupporting

confidence: 76%

Five-year outcome in the copaxone observatory: a nationwide cohort of patients with multiple sclerosis starting treatment with glatiramer acetate in France

Lebrun-Frénay¹,

Moulignier²,

Pierrot‐Deseilligny³

et al. 2019

J Neurol

View full text Add to dashboard Cite

The benefits provided by disease-modifying treatments in multiple sclerosis have been demonstrated in clinical trials, but the extent to which they can be extrapolated to everyday care is less clear, as are the long-term benefits of treatment. The objective of this prospective observational cohort study performed in France was to evaluate the effectiveness and safety of glatiramer acetate in patients with relapsing–remitting multiple sclerosis over a 5-year period. All neurologists in France were invited to participate and enroll adult patients starting a first treatment with brand glatiramer acetate 20 mg. Given the observational nature of the study, no fixed study visits were imposed; consultations took place according to the investigator’s normal practice. Occurrence of disease exacerbations and adverse events was documented and neurological disability evaluated with the EDSS at each consultation. Overall, 852 patients were analysable and 269 took glatiramer acetate continuously for 5 years. Median treatment duration was 3.4 years. Principal reasons for discontinuation were inadequate efficacy (38.9%), local tolerability (22.6%) and personal convenience (21.3%). Age, employment status, baseline EDSS score and number of previous exacerbations were variables associated with treatment persistence. The annualised exacerbation rate (5 years) was 0.41 [95% CI 0.39–0.44]; 316 patients (37.2%) remained exacerbation-free throughout. The risk of confirmed disability worsening (5 years) was 43.8% [95% CI 39.9–47.9%]. The most frequent adverse drug reactions were local injection site reactions (584 patients; 68.5%) and systemic immediate post-injection reactions (168 patients; 19.7%). Overall, these findings are consistent with those of previous clinical trials.Electronic supplementary materialThe online version of this article (10.1007/s00415-019-09211-5) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 76%

Five-year outcome in the copaxone observatory: a nationwide cohort of patients with multiple sclerosis starting treatment with glatiramer acetate in France

Lebrun-Frénay¹,

Moulignier²,

Pierrot‐Deseilligny³

et al. 2019

J Neurol

View full text Add to dashboard Cite

show abstract

“…Glatiramer acetate is one of the first therapeutics approved for treatment of relapsing-remitting MS. Although more than ten disease-modifying therapies (DMTs) with different mechanisms of action are now available for RRMS, GA has remained popular, especially considering some of the potentially life-threatening side effects of other DMTs [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

The influence of glatiramer acetate on Th17-immune response in multiple sclerosis

et al. 2020

View full text Add to dashboard Cite

Glatiramer acetate (GA) is approved for the treatment of multiple sclerosis (MS). However, the mechanism of action of GA in MS is still unclear. In particular, it is not known whether GA can modulate the pro-inflammatory Th17-type immune response in MS. We investigated the effects of original GA (Copaxone ® , Teva, Israel) and generic GA (Timexone ® , Biocad, Russia) on Th17- and Th1-type cytokine production in vitro in 25 patients with relapsing-remitting MS and 25 healthy subjects. Both original and generic GA at concentrations 50–200 μg/ml dose-dependently inhibited interleukin-17 and interferon-γ production by anti-CD3/anti-CD28-activated peripheral blood mononuclear cells from MS patients and healthy subjects. This effect of GA was reproduced using purified CD4 + T cells, suggesting that GA can directly modulate the functions of Th17 and Th1 cells. At high concentrations (100–200 μg/ml), GA also suppressed the production of Th17-differentiation cytokines (interleukin-1β and interleukin-6) by lipopolysaccharide (LPS)-activated dendritic cells (DCs). These GA/LPS-treated DCs induced lower interleukin-17 and interferon-γ production by autologous CD4 + T cells compared to LPS-treated DCs. These data suggest that GA can inhibit Th17-immune response and that this inhibitory effect is preferentially exercised by direct influence of GA on T cells. We also demonstrate a comparable ability of original and generic GA to modulate pro-inflammatory cytokine production.

show abstract

“…We speculate that these may include activation of GA-specific BCRs by cross-reactivity with antigen (possibly MBP) expressed in the acute MS lesion, leading to bystander suppression and possibly activation of other inhibitory T cell or B cell pathways. Thus, GA combines a mechanism of action that involves B cells, with a well-established and favorable safety profile [ 120 ]. Interestingly, patients with RRMS treated with GA can be subdivided into B cell responders and non-responders, based on the presence or absence of brain-specific B cells in the blood [ 100 ].…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Impact of Glatiramer Acetate on B Cell-Mediated Pathogenesis of Multiple Sclerosis

et al. 2018

View full text Add to dashboard Cite

Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells. Clinically, B cell-depleting agents show significant efficacy in MS. In addition, many disease-modifying therapies (DMTs) traditionally understood to target T cells are now known to influence B cell number and function. One of the earliest DMTs to be developed, glatiramer acetate (GA), has been shown to reduce the total frequency of B cells, plasmablasts, and memory B cells. It also appears to promote a shift toward reduced inflammation by increasing anti-inflammatory cytokine release and/or reducing pro-inflammatory cytokine release by B cells. In the authors’ opinion, this may be mediated by cross-reactivity of B cell receptors for GA with antigen (possibly myelin basic protein) expressed in the MS lesion. More research is required to further characterize the role of B cells and their bidirectional trafficking in the pathogenesis of MS. This may uncover novel targets for MS treatments and facilitate the development of B cell biomarkers of drug response.

show abstract

Long-term safety and tolerability of glatiramer acetate 20 mg in the treatment of relapsing forms of multiple sclerosis

Cited by 21 publications

References 20 publications

Five-year outcome in the copaxone observatory: a nationwide cohort of patients with multiple sclerosis starting treatment with glatiramer acetate in France

Five-year outcome in the copaxone observatory: a nationwide cohort of patients with multiple sclerosis starting treatment with glatiramer acetate in France

The influence of glatiramer acetate on Th17-immune response in multiple sclerosis

Impact of Glatiramer Acetate on B Cell-Mediated Pathogenesis of Multiple Sclerosis

Contact Info

Product

Resources

About