Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective
Abstract
BACKGROUND: Delayed-release dimethyl fumarate (also known as gastro-resistant dimethyl fumarate, hereafter dimethyl fumarate) is an oral disease-modifying therapy used for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS), an autoimmune chronic inflammatory condition of the central nervous system.
OBJECTIVE: The objective of this economic analysis was to compare cost-effectiveness of dimethyl fumarate with the alternatives used as first-line treatment of RRMS in Italy.
METHODS: The analysis was conducted from the Italian societal perspective. Health outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both health outcomes and costs were discounted at 3.5%. The cost-effectiveness analysis was conducted by adapting a Markov model, already used in previous similar economic analyses conducted in RRMS, to the Italian context. The Markov model estimated the clinical and economic consequences of treating RRMS patients with the following therapeutic options: dimethyl fumarate; interferon (IFN) beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data were retrieved from an elaboration of an already published mixed treatment comparison (MTC). Both direct and indirect costs (disability, treatment acquisition, administration, monitoring, relapses, adverse events) were included in the analysis. One-way and probabilistic sensitivity analyses were carried out and cost-effectiveness acceptability curves generated.
RESULTS: In the base-case analysis, dimethyl fumarate was more efficacious than alternatives, in terms of both survival (19.634 vs. 19.440-19.600 life years for alternatives), and quality-of-life-adjusted survival (6.526 vs. 5.143- 6.189 QALYs for alternatives). The total lifetime cost per patient treated with dimethyl fumarate (€ 954,286) was lower than that of the other DMTs included in the analysis. Therefore, dimethyl fumarate was dominant compared with all analyzed alternatives. Dimethyl fumarate was also the therapeutic option with the highest benefit on disease burden. In fact, costs of disability management were lower than those of all the other first-line drugs included in the analysis. The results of one-way deterministic sensitivity analysis and probabilistic sensitivity analysis confirmed the reliability of base-case results.
CONCLUSIONS: The results of the cost-effectiveness analysis confirm that dimethyl fumarate is an optimal first-line treatment for RRMS in Italy, compared with the other first-line alternatives included in the economic analysis, when evaluated from the societal perspective.
References
Canal N, Ghezzi A, Zaffaroni M. Sclerosi multipla. Attualità e prospettive. Milano: Elsevier Health Sciences, 2011
Associazione Italiana Sclerosi Multipla (AISM). Barometro Sclerosi Multipla, 2018
Kobelt G, Berg J, Lindgren P, et al. Costs and quality of life of patients with multiple sclerosis in Europe. J Neurol Neurosurg Psychiatry 2006; 77: 918-26; https://doi.org/10.1136/jnnp.2006.090365
Phillips CJ, Humphreys I. Assessing cost-effectiveness in the management of multiple sclerosis. Clinicoecon Outcomes Res 2009; 1: 61-78; https://doi.org/10.2147/CEOR.S4225
Kurtzke JF. A new scale for evaluating disability in multiple sclerosis. Neurology 1955; 5: 580-3; https://doi.org/10.1212/WNL.5.8.580
Battaglia M, Kobelt G, Ponzio M, et al. New insights into the burden and costs of multiple sclerosis in Europe: Results for Italy. Mult Scler 2017; 23 2: 104-16; https://doi.org/10.1177/1352458517708176
Thompson AJ, Baranzini SE, Geurts J, et al. Multiple sclerosis. Lancet 2018; 391: 1622-36; https://doi.org/10.1016/S0140-6736(18)30481-1
Johnson KP, Brooks BR, Cohen J a, 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. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995; 45: 1268-76; https://doi.org/10.1212/WNL.45.7.1268
Sibley WA. Interferon beta-1b in the treatment of multiple sclerosis: Final outcome of the randomized controlled trial. Neurology 1995; 45: 1277-85; https://doi.org/10.1212/WNL.45.7.1277
Ebers GC. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998; 352: 1498-504; https://doi.org/10.1016/S0140-6736(98)03334-0
Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285-94; https://doi.org/10.1002/ana.410390304
Tremlett HL, Oger J. Interrupted therapy: Stopping and switching of the β-interferons prescribed for MS. Neurology 2003; 61: 551-4; https://doi.org/10.1212/01.WNL.0000078885.05053.7D
European Medicines Agency – EMA. Peginterferon beta-1a (Plegridy). Summary of Product Characteristics. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002827/WC500170302.pdf (last accessed September 2018)
European Medicines Agency – EMA. Teriflunomide (Aubagio). Summary of Product Characteristics. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002514/WC500148682.pdf (last accessed September 2018)
European Medicines Agency – EMA. Dimethyl-fumarate (Tecfidera). Summary of Product Characteristics. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002601/WC500162069.pdf (last accessed September 2018)
Italian Medicines Agency – AIFA. Reimbursement and selling price of new packages of Tecfidera. Official Journal n. 19 of the Italian Republic of January 12, 2015
Italian Medicines Agency – AIFA. Reimbursement and selling price of new packages of Aubagio. Official Journal n. 187of the Italian Republic of August 13, 2014.
National Institute for Health and Care Excellence – NICE. Beta interferon and glatiramer acetate for the treatment of multiple sclerosis. Available at https://www.nice.org.uk/guidance/ta32 (last accessed September 2018)
National Institute for Health and Care Excellence – NICE. Fingolimod for the treatment of highly active relapsing–remitting multiple sclerosis. Available at https://www.nice.org.uk/guidance/ta254 (last accessed September 2018)
Gani R, Giovannoni G, Bates D, et al. Cost-effectiveness analyses of natalizumab (Tysabri®) compared with other disease-modifying therapies for people with highly active relapsing-remitting multiple sclerosis in the UK. Pharmacoeconomics 2008; 26: 617-27; https://doi.org/10.2165/00019053-200826070-00008
National Institute for Health and Care Excellence – NICE. Guide to the methods of technology appraisal 2013. Available at http://www.nice.org.uk/article/pmg9/chapter/foreword (last accessed September 2018)
Gold R, Kappos L, Arnold DL, et al. Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis. N Engl J Med 2012; 367: 1098-107; https://doi.org/10.1056/NEJMoa1114287
Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367: 1087-97; https://doi.org/10.1056/NEJMoa1206328
Weinshenker BG, Bass B, Rice GPA, et al. The Natural History Of Multiple Sclerosis: A Geographically Based Study. Brain 1989; 112: 1419-28; https://doi.org/10.1093/brain/112.6.1419
Kremenchutzky M, Rice GPA, Baskerville J, et al. The natural history of multiple sclerosis: A geographically based study 9: Observations on the progressive phase of the disease. Brain 2006; 129: 584-94; https://doi.org/10.1093/brain/awh721
Cottrell DA, Kremenchutzky M, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain 1999; 122: 641-7; https://doi.org/10.1093/brain/122.4.641
Patzold U, Pocklington PR. Course of multiple sclerosis. First results of a prospective study carried out of 102 MS patients from 1976-1980. Acta Neurol Scand 1982; 65: 248-66; https://doi.org/10.1111/j.1600-0404.1982.tb03084.x
UK Multiple Sclerosis Survey. Patient demographics, regression model on EDSS, relapse, type of MS and other variables on utility derived from EQ-5D. 2007
National Institute of Statistics of Italy (ISTAT). Mortality rates, 2016
Pokorski RJ. Long-term survival experience of patients with multiple sclerosis. J Insur Med 1997; 29: 101-6
Systematic review and mixed treatment comparison of MS therapies. Report (Data on file). December 2014
Hutchinson M, Fox RJ, Havrdova E, et al. Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing–remitting multiple sclerosis: a systematic review and mixed treatment comparison. Curr Med Res Opin 2014; 30: 613-27; https://doi.org/10.1185/03007995.2013.863755
Karampampa K, Gustavsson A, Miltenburger C, et al. Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from five European countries. Mult Scler 2012; 18: 7-15; https://doi.org/10.1177/1352458512441566
National Institute of Statistics of Italy (ISTAT). Inflation rates. Available at http://rivaluta.istat.it/Rivaluta (last accessed September 2018)
Italian Medicines Agency – AIFA. Renegotiation of the medicinal product for human use «Rebif». Determina n. 866/2018. Italian Official Journal n. 145, June 25th, 2018
Italian Medicines Agency – AIFA. Reimbursement and selling price of Betaferon. Official Journal n. 127 of the Italian Republic of June 02, 2000
Italian Medicines Agency – AIFA. Reimbursement and selling price of new packages of Betaferon. Official Journal n.279 of the Italian Republic Supplement n.250 of November 30, 2007
Italian Medicines Agency – AIFA. Reimbursement and selling price of new packages of Extavia. Official Journal n. 66 of the Italian Republic of March 20, 2009
Italian Medicines Agency – AIFA. Marketing authorization for the medicinal product “Copaxone”. Official Journal n. 106 of the Italian Republic of May 9, 2005
Clinical expert opinion to determine monitoring costs associated to multiple sclerosis disease modifying therapies. Data on file. June 2018
Garattini L, Castelnuovo E, Lanzeni D, et al. Duration and cost of general practitioner visits. The DYSCO project. Farmeconomia Health Economics and Therapeutic Pathways 2003; 4: 109-14; https://doi.org/10.7175/fe.v4i2.773
Italian Ministry of Health. Outpatient intervention tariffs. Italian Republic Official Gazette. Chapter n. 23; Supplement n. 8; 28 January 2013
Italian Ministry of Health, Department of Planning of the National Healthcare Service. Hospital activity and analysis of hospital discharge forms in 2014.
Italian Ministry of Health. Inpatient intervention tariffs. Italian Republic Official Gazette. Chapter n. 23; Supplement n. 8; 28 January 2013
Iannazzo S, Santoni L, Saleri C, et al. Cost-effectiveness analysis of peginterferon beta-1a in Italian relapsing remitting multiple sclerosis management. Farmeconomia Health Economics and Therapeutic Pathways 2016; 17: 13-36; https://doi.org/10.7175/fe.v17i2S.1230
Italian Medicines Agency – AIFA. Marketing authorization for the human medicinal product «Copemyl». Official Journal n. 6 of the Italian Republic of January 09, 2017
Messori A, Santarlasci B, Trippoli S, et al. Economic value of the drug and clinical benefit: state of the art of the methodology and application of a pharmacoeconomic algorithm. PharmacoEconomics Italian Research Articles 2003; 5: 53-67; https://doi.org/10.1007/BF03320605
Neumann PJ, Cohen JT, Weinstein MC. Updating Cost-Effectiveness — The Curious Resilience of the $50,000-per-QALY Threshold. N Engl J Med 2014; 371: 796-7; https://doi.org/10.1056/NEJMp1405158
Furneri G, Santoni L, Marchesi G, et al. Cost-Effectiveness Analysis of Delayed-Release Dimethyl-Fumarate In The Treatment of Relapsing-Remitting Multiple Sclerosis In Italy. Value Heal 2015; 18: A697; https://doi.org/10.1016/j.jval.2015.09.2598
Zhang X, Hay JW, Niu X. Cost Effectiveness of Fingolimod, Teriflunomide, Dimethyl Fumarate and Intramuscular Interferon-β1a in Relapsing-Remitting Multiple Sclerosis. CNS Drugs 2015; 29: 71-81; https://doi.org/10.1007/s40263-014-0207-x
Gasche D, Restovic G, Casado V, et al. Cost-Effectiveness Analysis of Delayed-Release Dimethyl Fumarate for The Treatment of Relapsing Remitting Multiple Sclerosis In Spain. Value Heal 2015; 18: A755; https://doi.org/10.1016/j.jval.2015.09.2931
Granfeldt D, Björstad Å, Öhrman S, et al. The cost effectiveness of delayed-release dimethyl fumarate versus interferon beta-1b in a Swedish setting. Value Heal 2015; 18: A757; https://doi.org/10.1016/j.jval.2015.09.2467
Silva Miguel L, de Sá J, Pinheiro B, et al. Cost-Utility Analysis of Delayed-Release Dimethyl Fumerate For The Treatment of Relapsing-Remitting Multiple Sclerosis In Portugal. Value Heal 2015; 18: A758; https://doi.org/10.1016/j.jval.2015.09.2471
Olsen J, Wiren A. Cost-Effectiveness of Dimethyl Fumarate Treatment for Relapsing-Remitting Multiple Sclerosis From A Danish Perspective. Value Heal 2015; 18: A758; https://doi.org/10.1016/j.jval.2015.09.2469
Chevalier J, Chamoux C, Hammès F, et al. Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective. PLoS One 2016; 11: e0150703; https://doi.org/10.1371/journal.pone.0150703
Lee AW. Review of mixed treatment comparisons in published systematic reviews shows marked increase since 2009. J Clin Epidemiol 2014; 67: 138-43; https://doi.org/10.1016/j.jclinepi.2013.07.014
Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: Report of the ISPOR task force on indirect treatment comparisons good research practices: Part 1. Value Heal 2011; 14: 417-28; https://doi.org/10.1016/j.jval.2011.04.002
Kobelt G, Berg J, Lindgren P, et al. Modeling the cost-effectiveness of a new treatment for MS (natalizumab) compared with current standard practice in Sweden. Mult Scler 2008; 14: 679-80; https://doi.org/10.1177/1352458507086667
Lee S, Baxter DC, Limone B, et al. Cost-effectiveness of fingolimod versus interferon beta-1a for relapsing remitting multiple sclerosis in the United States. J Med Econ 2012; 15: 1088-96; https://doi.org/10.3111/13696998.2012.693553
Chiao E, Meyer K. Cost effectiveness and budget impact of natalizumab in patients with relapsing multiple sclerosis. Curr Med Res Opin 2009; 25: 1445-54; https://doi.org/10.1185/03007990902876040
Giovannoni G, Tomic D, Bright JR, et al. “No evident disease activity”: The use of combined assessments in the management of patients with multiple sclerosis. Mult Scler J 2017; 23: 1179-87; https://doi.org/10.1177/1352458517703193
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