Clinical Data Associated With the Therapeutic Response to Glatiramer Acetate in Multiple Sclerosis Patients
DOI:
https://doi.org/10.17140/NOJ-3-121Keywords:
Multiple sclerosis, Glatiramer acetate, Clinical response, Predictive factorsAbstract
Background: The increasing appearance of new drugs is making more difficult the choice of treatment in multiple sclerosis. According to different criteria, between 20 to 50% of the patients with multiple sclerosis (MS) treated with the classical disease modify treatments (DMT) will have an incomplete response and will need a change for more aggressive therapies. For this reason it is of great importance to improve the selection process in these patients to avoid treatment failures, side-effects and unnecessary risks. The utility of clinical and epidemiological data for the prediction of the therapeutic response to the different MS treatments, and particularly to glatiramer acetate (GA), is insufficient and contradictory.
Objective: To develop a predictive model of clinical data associated with the clinical response to GA.
Methods: Observational retrospective study by reviewing medical charts from October/2002 to February/2012. Data analysis was conducted from February/2014 to February/2015.
Inclusion criteria: Relapsing-remitting multiple sclerosis (RRMS McDonald 2010) with ≥1 relapses in the previous 2 years, and ≥2 years of treatment with GA. All the patients included in this study were treated with GA 20 mg injected subcutaneously once daily as the newer formulation of GA 40 mg 3 times weekly was not approved at the time of the study.
Definitions:
Responders: ≤1 relapse and no disability progression;
Non-responders: ≥2 relapses and/or disability progression.
Disability progression: EDSS increase ≥1.5 points if basal EDSS=0; increase ≥1 if basal EDSS=1-5; increase ≥0.5 if basal EDSS ≥5.5.
Statistical analysis: logistic regression.
Association variable: odds ratio.
Results: Two hundred and four subjects included. Responders: 137 (67.5%). Number of relapses in the 2 years before GA onset was associated with a worse clinical response (odds ratio (OR): 1.4; IC 95%: 1.12-1.74%). Accuracy of this model (AUC: 63.5%; IC 95%: 56.2- 70.7%);
Diagnostic parameters: Sensitivity: 40%; specificity: 79.8%, positive predictive value: 78.6; negative predictive value: 41.7.
Conclusions: GA was associated with a better response in Relapsing-remitting multiple sclerosis (RRMS) patients with low-moderate disease activity. This model could be improved incorporating serological, genetic and imaging data.
References
Benito-León J, Morales JM, Rivera-Navarro J, et al. A review about the impact of multiple sclerosis on health-related quality of life. Disabil Rehabil. 2003; 25(23): 1291-1303. doi: 10.1080/09638280310001608591
Mitchell AJ, Benito-León J, González J-MM, Rivera-Navarro J. Quality of life and its assessment in multiple sclerosis: Integrating physical and psychological components of wellbeing. Lancet Neurol. 2005; 4(9): 556-566. doi: 10.1016/ S1474-4422(05)70166-6
Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000; 343(13): 938-952.
Río J, Castilló J, Rovira A, et al. Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler Houndmills Basingstoke Engl. 2009; 15(7): 848-853. doi: 10.1177/1352458509104591
Río J, Nos C, Tintoré M, et al.Assessment of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta: Implications for clinical trials. Ann Neurol. 2002; 52(4): 400-406.
Río J, Nos C, Tintoré M, Téllez N, et al. Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients. Ann Neurol. 2006; 59(2): 344-352. doi: 10.1002/ana. 20740
Teitelbaum D, Meshorer A, Hirshfeld T, Arnon R, Sela M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur J Immunol. 1971; 1(4): 242-248. doi: 10.1002/eji.1830010406
Arnon R, Sela M, Teitelbaum D. New insights into the mechanism of action of copolymer 1 in experimental allergic encephalomyelitis and multiple sclerosis. J Neurol. 1996; 243(4 Suppl 1): S8-S13. doi: 10.1007/BF00873696
Bornstein MB, Miller A, Slagle S, et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med. 1987; 317(7): 408-414. doi: 10.1056/NEJM198708133170703
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(7): 1268-1276. doi: 10. 1212/WNL.45. 7. 1268
Comi G, Filippi M, Wolinsky JS. 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. European/Canadian Glatiramer Acetate Study Group. Ann Neurol. 2001; 49(3): 290-297. doi: 10.1002/ana.64
Comi G, Martinelli V, Rodegher M, et al. Effect of glatiramer 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(9700): 1503-1511. doi: 10.1016/S0140-6736(09)61259-9
Ford CC, Johnson KP, Lisak RP, Panitch HS, Shifronis G, Wolinsky JS. A prospective open-label study of glatiramer acetate: Over a decade of continuous use in multiple sclerosis patients. Mult Scler Houndmills Basingstoke Engl. 2006; 12(3): 309-320. doi: 10.1191/135248506ms1318oa
Johnson KP, Brooks BR, Cohen JA, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology. 1998; 50(3): 701-708. doi: 10. 1212/ WNL. 50. 3. 701
Johnson KP, Brooks BR, Ford CC, et al. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Mult Scler Houndmills Basingstoke Engl. 2000; 6(4): 255-266.
Ford C, Goodman AD, Johnson K, 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 Houndmills Basingstoke Engl. 2010; 16(3): 342-350. doi: 10.1177/1352458509358088
Khan O, Rieckmann P, Boyko A, Selmaj K, Zivadinov R. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol. 2013; 73(6): 705-713. doi: 10.1002/ana.23938
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 acetate low-frequency administration open-label extension study. Mult Scler. 2016. doi: 10.1177/ 1352458516664033
Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69(2): 292-302. doi: 10.1002/ ana.22366
Fusco C, Andreone V, Coppola G, et al. HLA-DRB1*1501 and response to copolymer-1 therapy in relapsing-remitting multiple sclerosis. Neurology. 2001; 57(11): 1976-1979.
Grossman I, Avidan N, Singer C, et al. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers. Pharmacogenet Genomics. 2007; 17(8): 657- 666.
Domenech JM. Macro !DT for SPSS Statistics. Diagnostic Tests [computer program]. V2009.06.26. Bellaterra, Barcelona, Spain: Universitat Autònoma de Barcelona; 2009. Web site. http://www.metodo.uab.cat/macros.htm. Accessed September 7, 2016.
Martinelli Boneschi F, Rovaris M, et al. Effects of glatiramer acetate on relapse rate and accumulated disability in multiple sclerosis: Meta-analysis of three double-blind, randomized, placebo-controlled clinical trials. Mult Scler Houndmills Basingstoke Engl. 2003; 9(4): 349-355. doi: 10.1191/1352458503ms932oa
Romeo M, Martinelli-Boneschi F, Rodegher M, et al. Clinical and MRI predictors of response to interferon-beta and glatiramer acetate in relapsing-remitting multiple sclerosis patients. Eur J Neurol Off J Eur Fed Neurol Soc. 2013; 20(7): 1060-1067. doi: 10.1111/ene.12119
Fernández-Fernández Ó, Garcia-Trujillo L, Guerrero-Fernández M, et al. The effectiveness of glatiramer acetate in clinical practice: An observational study. Rev Neurol. 2012; 54(1): 1-9. Web site. http://www.revneurol.com/sec/resumen. php?or=pubmed&id=2011567. Accessed September 7, 2016.
Pereira VCSR, Malfetano FR, Meira ID, et al. Clinical response to interferon beta and glatiramer acetate in multiple sclerosis patients: A Brazilian cohort. Arq Neuropsiquiatr. 2012; 70(10): 774-779. doi: 10.1590/S0004-282X2012001000005
Sindic CJM, Seeldrayers P, Vande Gaer L, et al. Long-term follow up of glatiramer acetate compassionate use in Belgium. Acta Neurol Belg. 2005; 105(2): 81-85. Web site. http://www. actaneurologica.be/acta/download/2005-2/05-SIndic%20et%20 al.pdf. Accessed September 7, 2016.
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Neuro (NEURO) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.