Question

current literature review of a specific aspect of Glatiramer(copaxone)

- come up with 5 topics on a current literature review of the drug Glatiramer(copaxone)

Answer 1

Current literature review of the drug Glatiramer(copaxone)

1. Comparing the Biological Impact of Glatiramer Acetate with the Biological Impact of a Generic - Fadi Towfic,Jason M. Funt, Kevin D. Fowler et.al

For decades, policies regarding generic medicines have sought to provide patients with economical access to safe and effective drugs, while encouraging the development of new therapies. This balance is becoming more challenging for physicians and regulators as biologics and non-biological complex drugs (NBCDs) such as glatiramer acetate demonstrate remarkable efficacy, because generics for these medicines are more difficult to assess. We sought to develop computational methods that use transcriptional profiles to compare branded medicines to generics, robustly characterizing differences in biological impact. We combined multiple computational methods to determine whether differentially expressed genes result from random variation, or point to consistent differences in biological impact of the generic compared to the branded medicine. We applied these methods to analyze gene expression data from mouse splenocytes exposed to either branded glatiramer acetate or a generic. The computational methods identified extensive evidence that branded glatiramer acetate has a more consistent biological impact across batches than the generic, and has a distinct impact on regulatory T cells and myeloid lineage cells. In summary, we developed a computational pipeline that integrates multiple methods to compare two medicines in an innovative way. This pipeline, and the specific findings distinguishing branded glatiramer acetate from a generic, can help physicians and regulators take appropriate steps to ensure safety and efficacy.

2. Two decades of subcutaneous glatiramer acetate injection: current role of the standard dose, and new high-dose low-frequency glatiramer acetate in relapsing–remitting multiple sclerosis treatment. - Matteo Caporro, Giulio Disanto et.al

Glatiramer acetate, a synthetic amino acid polymer analog of myelin basic protein, is one of the first approved drugs for the treatment of relapsing–remitting multiple sclerosis. Several clinical trials have shown consistent and sustained efficacy of glatiramer acetate 20 mg subcutaneously daily in reducing relapses and new demyelinating lesions on magnetic resonance imaging in patients with relapsing–remitting multiple sclerosis, as well as comparable efficacy to high-dose interferon beta. Some preclinical and clinical data suggest a neuroprotective role for glatiramer acetate in multiple sclerosis. Glatiramer acetate is associated with a relatively favorable side-effect profile, and importantly this was confirmed also during long-term use. Glatiramer acetate is the only multiple sclerosis treatment compound that has gained the US Food and Drug Administration pregnancy category B. All these data support its current use as a first-line treatment option for patients with clinical isolated syndrome or relapsing–remitting multiple sclerosis. More recent data have shown that high-dose glatiramer acetate (ie, 40 mg) given three times weekly is effective, safe, and well tolerated in the treatment of relapsing–remitting multiple sclerosis, prompting the approval of this dosage in the US in early 2014. This high-dose, lower-frequency glatiramer acetate might represent a new, more convenient regimen of administration, and this might enhance patients’ adherence to the treatment, crucial for optimal disease control.

3. Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis
Nitin J. Karandikar, Michael P. Crawford, Brenchley et.al.

Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine that is used therapeutically in patients with multiple sclerosis (MS). To investigate the mechanism of the drug’s immunomodulatory effect, we used immunophenotypic approaches to characterize the precise nature of GA-induced T cell responses. We demonstrate here that healthy individuals and untreated MS patients exhibit prominent T cell proliferative responses to GA. However, these responses are different in distinct subsets of T cells. Whereas GA-induced CD4+ T cell responses are comparable in healthy individuals and MS patients, CD8+ T cell responses are significantly lower in untreated MS patients. Treatment with GA results in upregulation of these CD8+ responses with restoration to levels observed in healthy individuals. Both CD4+ and CD8+ GA-specific responses are HLA-restricted. GA therapy also induces a change in the cytokine profile of GA-specific CD4+ and CD8+ T cells. This study provides the first direct immunophenotypic evidence, to our knowledge, of GA-specific CD8+ T cell responses and their upregulation during the course of therapy, which may suggest a role for these responses in the immunomodulatory effects of the drug.

4. Spasticity in multiple sclerosis and role of glatiramer acetate treatment - Jose Eustasio Meca-Lallana,Rocío Hernández-Clares and Ester Carreón-Guarnizol.

Spasticity is one of the most disabling and difficult-to-treat symptoms shown by patients with multiple sclerosis, who often show a suboptimal and unsatisfactory response to classic treatment and new available nonpharmacological alternatives. Due to the progressive nature of this condition, the early management should be essential to improve long-term outcomes. We performed a narrative literature review of the contribution of spasticity to the burden of multiple sclerosis and the potential role of classic disease-modifying drugs. Added to the underlying pathophysiology of spasticity, certain external factors and drugs such as interferon may exacerbate the existing condition, hence their awareness is crucial as part of an effective management of spasticity. Furthermore, the evidence for the effectiveness of glatiramer acetate in preventing spasticity in naïve patients and in those switching from interferon should not be ignored. This literature review proposes the examination of spasticity and the influence of classic disease-modifying agents on the level of existing condition among the variables to be considered when deciding on therapy for multiple sclerosis in clinical practice.

5. Fatigue Improvement after Switching Multiple Sclerosis Treatment from Interferon-? to Glatiramer Acetate in Clinical Practice. - Meca-Lallana J, Hernández L et. al.

The immunomodulatory effect of glatiramer acetate may help in reducing multiple sclerosis (MS)-related fatigue; however, evidence to prove this notion especially after switching from another immunomodulatory therapy is limited. We assessed the 6-month effect of glatiramer acetate on MS-related fatigue in patients switching from interferon-? (IFN-?) in clinical practice. This was an observational study including 54 patients with relapsing-remitting MS that showed moderate/severe fatigue primarily caused by MS before switching from IFN-? to glatiramer acetate and received glatiramer acetate for ?6 months in daily practice. Study data were retrospectively collected through chart review at treatment switch and over the following 6 months on glatiramer acetate. Over the 6-month administration of glatiramer acetate, scores on the Modified Fatigue Impact Scale decreased: overall (p < 0.001), physical scale (p < 0.001), cognitive scale (p < 0.001), and psychosocial scale (p < 0.001). The Work Productivity and Activity Impairment Questionnaire showed improvements in work (p = 0.009) and other daily activity impairment (p < 0.001). Health-related quality of life as per the Multiple Sclerosis Impact Scale also improved: physical score (p < 0.001) and psychological score (p < 0.001). Patients with moderate/severe fatigue switching from IFN-? to glatiramer acetate may benefit from fatigue improvements that contribute to reduce their work/activity impairment and improve their quality of life.