Advertisement

CNS Drugs

, Volume 29, Issue 5, pp 425–432 | Cite as

Glatiramer Acetate 40 mg/mL in Relapsing–Remitting Multiple Sclerosis: A Review

  • Kate McKeage
Adis Drug Evaluation

Abstract

Glatiramer acetate (Copaxone®) is a synthetic analogue of myelin basic protein, which is thought to be involved in the pathogenesis of multiple sclerosis (MS). The therapeutic effects of the drug in the treatment of MS are thought to be via immunomodulation and neuroprotection. Subcutaneous glatiramer acetate 20 mg/mL once daily is approved in several countries for the treatment of relapsing forms of MS. Recently, a high-concentration formulation of glatiramer acetate 40 mg/mL administered three times weekly was approved in the USA and several European countries in the same indication. This article reviews the efficacy and tolerability of the high-concentration regimen. In the randomized, phase III GALA study in patients with relapsing–remitting MS (RRMS), glatiramer acetate 40 mg/mL three times weekly reduced annualized relapse rates significantly more than placebo, and indirect comparisons indicate that the efficacy of the three-times-weekly regimen is similar to that of the 20 mg/mL once-daily regimen. Results of the randomized, phase IIIb GLACIER study in patients with RRMS demonstrated that the three-times-weekly regimen reduced the risk of injection-site reactions by 50 % and was associated with numerically greater patient convenience scores than the once-daily regimen. Thus, in the treatment of RRMS, glatiramer acetate 40 mg/mL three times weekly is effective and provides a better tolerated and possibly more convenient option than the once-daily regimen.

Keywords

Expand Disability Status Scale Glatiramer Acetate Glatiramer Clinically Isolate Syndrome Annualize Relapse Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit. Kate McKeage is a salaried employee of Adis/Springer.

References

  1. 1.
    Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012;122:1180–8.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    A consensus paper by the multiple sclerosis coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. 2014 July. http://www.mscare.org/?page=dmt. Accessed 26 Mar 2015.
  3. 3.
    Lublin FD. New multiple sclerosis phenotypic classification. Eur Neurol. 2014;72(Suppl 1):1–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Scott L. Glatiramer acetate: a review of Its use in patients with relapsing–remitting multiple sclerosis and in delaying the onset of clinically definite multiple sclerosis. CNS Drugs. 2013;27(11):971–88.PubMedCrossRefGoogle Scholar
  5. 5.
    Jalilian B, Einarsson HB, Vorup-Jensen T. Glatiramer acetate in treatment of multiple sclerosis: a toolbox of random co-polymers for targeting inflammatory mechanisms of both the innate and adaptive immune system? Int J Mol Sci. 2012;13(11):14579–605.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Aharoni R. The mechanism of action of glatiramer acetate in multiple sclerosis and beyond. Autoimmun Rev. 2013;12(5):543–53.PubMedCrossRefGoogle Scholar
  7. 7.
    Blanchette F, Neuhaus O. Glatiramer acetate: evidence for a dual mechanism of action. J Neurol. 2008;255(1):26–36.PubMedCrossRefGoogle Scholar
  8. 8.
    Arnon R, Aharoni R. Neurogenesis and neuroprotection in the CNS: fundamental elements in the effect of glatiramer acetate on treatment of autoimmune neurological disorders. Mol Neurobiol. 2007;36(3):245–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Messina S, Patti F. The pharmacokinetics of glatiramer acetate for multiple sclerosis treatment. Expert Opin Drug Metab Toxicol. 2013;9(10):1349–59.PubMedCrossRefGoogle Scholar
  10. 10.
    Teva Pharmaceuticals USA Inc. Copaxone (glatiramer acetate injection): prescribing information. Philadelphia (PA): Teva Pharmaceuticals; 2014.Google Scholar
  11. 11.
    Medicines and Healthcare Products Regulatory Agency. Copaxone 40 mg/ml solution for injection: summary of product characteristics 2015. http://www.mhra.gov.uk/spc-pil/index.htm?prodName=COPAXONE. Accessed 26 Mar 2015.
  12. 12.
    Lublin FD, Cofield SS, Cutter GR, et al. Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol. 2013;73:327–40.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Comi G, Filippi M, Wolinsky JS, et al. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol. 2001;49:290–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing–remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology. 1995;45:1268–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Mikol DD, Barkhof F, Chang P, et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol. 2008;7(10):903–14.PubMedCrossRefGoogle Scholar
  16. 16.
    O’Connor P, Filippi M, Arnason B, et al. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing–remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 2009;8:889–97.PubMedCrossRefGoogle Scholar
  17. 17.
    Cadavid D, Wolansky LJ, Skurmick J, et al. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology. 2009;72:1976–83.PubMedCrossRefGoogle Scholar
  18. 18.
    Ford C, Goodman AD, Johnson KP, et al. Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate. Mult Scler. 2010;16:342–50.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Ford C, Ladkani D. Twenty years of continuous treatment of multiple sclerosis with glatiramer acetate 20 mg daily: long-term clinical results of the US open-label extension study [abstract plus poster P577]. Mult Scler. 2013;19(Suppl 1):242.Google Scholar
  20. 20.
    Comi G, Martinelli V, Rodegher M, et al. Effect of glatirmaer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1503–11.PubMedCrossRefGoogle Scholar
  21. 21.
    Comi G, Cohen JA, Arnold DL, et al. Phase III dose-comparison study of glatiramer acetate for multiple sclerosis. Ann Neurol. 2011;69(1):75–82.PubMedCrossRefGoogle Scholar
  22. 22.
    Khan O, Rieckmann P, Boyko A, et al. Three times weekly glatiramer acetate in relapsing–remitting multiple sclerosis. Ann Neurol. 2013;73(6):705–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Khan O, Rieckmann P, Boyko A, et al. Efficacy and safety of a three-times weekly dosing regimen of glatiramer acetate in relapsing–remitting multiple sclerosis patients: 3-year results of the glatiramer actetate low-frequency administration (GALA) open-label extension study [abstract no. P7.273]. In: American Academy of Neurology Annual Meeting. 2015.Google Scholar
  24. 24.
    Zivadinov R, Dwyer M, Barkay H, et al. Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense “black holes”: a post hoc magnetic resonance imaging analysis. J Neurol. 2015;262:648–53.PubMedCrossRefGoogle Scholar
  25. 25.
    Cutter G, Wolinsky JS, Comi G, et al. Comparable clinical and MRI efficacy of glatiramer acetate 40 mg/mL TIW and 20 mg/mL QD: results of a systematic review and meta-analysis [abstract no. P053]. Mult Scler. 2014;20(Suppl 1):90–1.Google Scholar
  26. 26.
    Cutter G, Wolinsky JS, Comi G, et al. Indirect comparison of glatiramer acetate 40 mg/mL TIW and 20 mg/mL QD dosing regimen effects on relapse rate: results of a predictive statistical model [abstract no. P100]. Mult Scler. 2014;20(Suppl 1):112.Google Scholar
  27. 27.
    Wolinsky JS, Dietrich DW, Borresen TE, et al. GLACIER: open-label, randomized safety/tolerability study of glatiramer acetate 40 mg/mL three times weekly versus 20 mg/mL daily in RRMS [abstract no. FC3.2]. Mult Scler. 2014;20(Suppl 1):43–4.Google Scholar
  28. 28.
    Wolinsky JS, Sidi Y, Steinerman JR, et al. Reduced frequency and severity of injection site reactions with glatiramer acetate 40 mg/mL three times weekly dosing [abstract no. P306 plus poster]. Mult Scler. 2014;20(Suppl 1):203–4.Google Scholar
  29. 29.
    Wynn D, Kolodny S, Rubinchick S, et al. Patient experience with glatiramer acetate 40 mg/1 mL three-times weekly treatment for relapsing–remitting multiple sclerosis: results from the GLACIER extension study [abstract no. P7.218]. In: American Academy of Neurology Annual Meeting. 2015.Google Scholar
  30. 30.
    Wolinsky JS, Borresen TE, Dietrich DW, et al. Convenience of glatiramer acetate 40 mg/mL three times weekly: evidence from the GLACIER study [abstract no. P080 plus poster]. Mult Scler. 2014;20(Suppl 1):103.Google Scholar
  31. 31.
    Tanasescu R, Ionete C, Chou I-J, et al. Advances in the treatment of relapsing–remitting multiple sclerosis. Biomed J. 2014;37:41–9.PubMedCrossRefGoogle Scholar
  32. 32.
    National Clinical Advisory Board of the National Multiple Sclerosis Society. Treatment recommendations for physicians: disease management consensus statement. 2008. http://www.nationalmssociety.org. Accessed 23 Mar 2015.
  33. 33.
    Stewart TM, Tran ZV. Injectable multiple sclerosis medications: a patient survey of factors associated with injection-site reactions. Int J MS Care. 2012;14:46–53.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Di Battista G, Bertolotto A, Gasperini C, et al. Multiple sclerosis state of the art (SMART): a qualitative and quantitative analysis of therapy’s adherence, hospital reliability’s perception, and services provided quality. Mult Scler Int. 2014. doi: 10.1155/2014/752318.
  35. 35.
    Tan H, Cai Q, Agarwal S, et al. Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis. Adv Ther. 2011;28:51–61.PubMedCrossRefGoogle Scholar
  36. 36.
    Remington G, Rodriguez Y, Logan D, et al. Facilitating medication adherence in patients with multiple sclerosis. Int J MS Care. 2013;15:36–45.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Chiarini M, Sottini A, Ghidini C, et al. Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate. Mult Scler. 2010;16(2):218–27.PubMedCrossRefGoogle Scholar
  38. 38.
    Burger D, Molnarfi N, Weber MS, et al. Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1β in human monocytes and multiple sclerosis. Proc Natl Acad Sci USA. 2009;106(11):4355–9.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Pul R, Morbiducci F, Škuljec J, et al. Glatiramer acetate increases phagocytic activity of human monocytes in vitro and in multiple sclerosis patients. PLoS One. 2012;7(12):e51867.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Starossom SC, Veremeyko T, Dukhinova M, et al. Glatiramer acetate (Copaxone) modulates platelet activation and inhibits thrombin-induced calcium influx: possible role of Copaxone in targeting platelets during autoimmune neuroinflammation. PLoS One. 2014;9(5):e96256.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Waschbisch A, Atiya M, Linker RA, et al. Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis. PLoS ONE. 2011;6(9):e24604.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations