Long-term treatment of multiple sclerosis with glatiramer acetate: Natural history of the subtypes of anti-glatiramer acetate antibodies and their correlation with clinical efficacy

Karussis, Dimitros; Teitelbaum, Dvora; Sicsic, Camille; Brenner, Talma

doi:10.1016/j.jneuroim.2010.01.009

Cited by 46 publications

(32 citation statements)

References 36 publications

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“…Unlike antibodies against IFNβ, [50] antibodies against glatiramer acetate may not dampen its clinical effect. [51] In this regard, Brenner et al [52] reported that relapse-free patients displayed higher antibody titres against glatiramer acetate than patients with an active disease course under glatiramer acetate treatment. In an animal model of CNS demyelinating disease, glatiramer acetate-specific antibodies were shown to promote myelin repair, [53] thus indicating a beneficial rather than harmful role of antibodies against glatiramer acetate.…”

Section: Mechanism(s) Of Action Of Glatiramer Acetate: An Updatementioning

confidence: 99%

Glatiramer Acetate in the Treatment of Multiple Sclerosis

Neuhaus²,

et al. 2011

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Glatiramer acetate is a synthetic, random copolymer widely used as a first-line agent for the treatment of relapsing-remitting multiple sclerosis (MS). While earlier studies primarily attributed its clinical effect to a shift in the cytokine secretion of CD4+ T helper (Th) cells, growing evidence in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), suggests that glatiramer acetate treatment is associated with a broader immunomodulatory effect on cells of both the innate and adaptive immune system. To date, glatiramer acetate-mediated modulation of antigen-presenting cells (APC) such as monocytes and dendritic cells, CD4+ Th cells, CD8+ T cells, Foxp3+ regulatory T cells and antibody production by plasma cells have been reported; in addition, most recent investigations indicate that glatiramer acetate treatment may also promote regulatory B-cell properties. Experimental evidence suggests that, among these diverse effects, a fostering interplay between anti-inflammatory T-cell populations and regulatory type II APC may be the central axis in glatiramer acetate-mediated immune modulation of CNS autoimmune disease. Besides altering inflammatory processes, glatiramer acetate could exert direct neuroprotective and/or neuroregenerative properties, which could be of relevance for the treatment of MS, but even more so for primarily neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease. In this review, we provide a comprehensive and critical overview of established and recent findings aiming to elucidate the complex mechanism of action of glatiramer acetate.

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Section: Mechanism(s) Of Action Of Glatiramer Acetate: An Updatementioning

confidence: 99%

Glatiramer Acetate in the Treatment of Multiple Sclerosis

Neuhaus²,

et al. 2011

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“…There is also evidence to suggest that patients with neutralizing antibodies to natalizumab may have recurrent disease activity [53]. The significance of glatiramer-binding antibodies is unclear, but some studies have suggested that low-titer glatiramer antibodies may be associated with better outcomes [53,54].…”

Section: B Cells and Immunoglobulinsmentioning

confidence: 99%

Biomarkers of disease activity in multiple sclerosis

Graber

Dhib‐Jalbut²

2011

Journal of the Neurological Sciences

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“…As GA structure is based on MBP, patients with MS may have cross-reactive IgG antibodies [15]. However, other authors found GA sIgG, but not against MBP, in treated patients [16]. As GA is composed of synthetic polypeptides of four amino acids, it is possible that these polypeptides share not only epitopes with MBP but also with other proteins.…”

Section: Discussionmentioning

confidence: 99%

IgE-Mediated Allergic Reactions after the First Administration of Glatiramer Acetate in Patients with Multiple Sclerosis

Corominas

Postigo²,

Cardona³

et al. 2014

Int Arch Allergy Immunol

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Background: Immediate adverse reactions to glatiramer acetate (GA), a drug used in the treatment of patients with multiple sclerosis (MS), have been poorly investigated. We studied 3 MS patients who presented adverse reactions following GA administration. Two of them experienced severe anaphylactic reactions after the first administration and the other an eyelid edema upon reintroduction 6 months after GA withdrawal. Methods: Skin prick tests (SPT) to GA and mannitol were performed on all 3 patients and in 10 atopic controls. Specific IgE (sIgE) levels to GA, myelin basic protein (MBP) and MBP fragments were assessed in all 3 patients, 6 MS patients treated with GA for more than 6 month and 10 healthy donors. Specific IgG (sIgG) to GA was also quantified in the three study groups. Both sIgE and sIgG were determined by means of the UniCAP 100 assay. Results: SPT and sIgE to GA were positive only in the 3 patients with adverse reactions while sIgE to mannitol was negative in all. sIgE tests against MBP and its fragments were negative in all individuals. Similar levels of sIgG to GA were found in all studied subjects. Conclusion: These results demonstrate the significance of sIgE in allergic reactions to GA presented by these patients and suggest the importance of strict surveillance during administration of the first GA doses.

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Long-term treatment of multiple sclerosis with glatiramer acetate: Natural history of the subtypes of anti-glatiramer acetate antibodies and their correlation with clinical efficacy

Cited by 46 publications

References 36 publications

Glatiramer Acetate in the Treatment of Multiple Sclerosis

Glatiramer Acetate in the Treatment of Multiple Sclerosis

Biomarkers of disease activity in multiple sclerosis

IgE-Mediated Allergic Reactions after the First Administration of Glatiramer Acetate in Patients with Multiple Sclerosis

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