Cost-Effectiveness of Dimethyl Fumarate Compared to Teriflunomide for Relapsing Remitting Multiple Sclerosis Patients in Italy

Lorenzo Giovanni Mantovani, Paolo Angelo Cortesi, Alessandra Cardillo, Laura Santoni, Luca Prosperini



BACKGROUND: The objective of this economic analysis was to compare the cost-effectiveness of dimethyl fumarate vs teriflunomide for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) in the Italian setting. Additionally, the cost-effectiveness analysis was used to predict some patient-relevant outcomes such as burden of relapses and survival with disability over time.

METHODS: A Markov model was used to conduct the cost-effectiveness analysis. The model measured health outcomes and costs of RRMS patients treated with either dimethyl fumarate or teriflunomide. Data from a published mixed treatment comparison were used for efficacy and safety input. Local economic data were used to calculate costs. A supplementary analysis was carried out to assess ICER variability over time from the Italian National Healthcare Service (NHS) and societal perspectives. Further analyses were conducted to compare clinical effectiveness of the alternatives over time, in terms of incidence of relapses, proportion of patients with EDSS (Expanded Disability Status Scale) score ≤3 and EDSS score ≥6.

RESULTS: In the base-case analysis (lifetime horizon; societal perspective) dimethyl fumarate was dominant over teriflunomide (6.526 vs 5.953 QALYs – quality-adjusted life-years; € 1.01 M vs € 1.03 M). The most relevant cost savings (per-patient) with dimethyl fumarate were related to relapses (-€ 5,096), inpatient care (-€ 5,767), informal care (-€ 9,603), long-term absence/early retirement (-€ 14,187). The additional analysis of ICER by time horizon shows that dimethyl fumarate is cost-effective vs teriflunomide (i.e., ICER <€ 50,000 per QALY gained) at already 6 years and at 15 years in societal or NHS perspectives, respectively. Results favoured dimethyl fumarate vs teriflunomide also for: cumulative burden of relapses (-0.23 and -1.37 relapses saved per patient already at 1 year and 10 years, respectively), proportion of patients with mild disability (+4.0% at 10 years), proportion of patients with severe disability (-4.0% at 10 years).

CONCLUSIONS: Dimethyl fumarate is dominant (societal perspective), or cost-effective (NHS perspective), referring to a threshold of € 50,000 per QALY gained, vs teriflunomide for the first-line treatment of RRMS, in the Italian setting.


Dimethyl Fumarate; Teriflunomide; Relapsing-Remitting Multiple Sclerosis; Cost-Effectiveness; Quality-Adjusted Survival

Full Text



  • Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler 2020; 26: 1816;
  • Italian Ministry of Health. Multiple Sclerosis. Available at: (last accessed )
  • Associazione Italiana Sclerosi Multipla (AISM): BAROMETRO della SCLEROSI MULTIPLA 2019. Available at: (last accessed )
  • Huang WJ, Chen WW, Zhang X. Multiple sclerosis: Pathology, diagnosis and treatments (review). Exp Ther Med 2017; 13: 3163-6;
  • Wallin MT, Culpepper WJ, Nichols E, et al. Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18: 269-85;
  • Kobelt G, Thompson A, Berg J, et al. New insights into the burden and costs of multiple sclerosis in Europe. Mult Scler 2017; 23: 1123-36;
  • 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;
  • Phillips CJ, Humphreys I. Assessing cost-effectiveness in the management of multiple sclerosis. Clinicoecon Outcomes Res 2009; 1: 61-78;
  • Dutta R, Trapp BD. Relapsing and progressive forms of multiple sclerosis – insights from pathology. Curr Opin Neurol 2015 ;27: 271-8;
  • Tremlett HL, Oger J. Interrupted therapy: Stopping and switching of the β-interferons prescribed for MS. Neurology 2003; 61: 551-4;
  • Mehr SR, Zimmerman MP. Reviewing the unmet needs of patients with multiple sclerosis. Am Heal Drug Benefits 2015; 8: 426-31
  • Miller AE, Rhoades RW. Treatment of relapsing-remitting multiple sclerosis: current approaches and unmet needs. Curr Opin Neurol 2012; 25: S4-10;
  • 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
  • European Medicines Agency (EMA). Dimethyl-fumarate (Tecfidera). Summary of product characteristics. Available at: (last accessed...)
  • Italian Medicines Agency (AIFA). Reimbursement and selling price of new packages of Aubagio. Official Journal n. 187of the Italian Republic of August 13, 2014
  • European Medicines Agency (EMA). Teriflunomide (Aubagio). Summary of product characteristics. Available at: (last accessed...)
  • National Institute for Health and Care Excellence (NICE). Beta interferon and glatiramer acetate for the treatment of multiple sclerosis. Available at: (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: (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;
  • Furneri G, Santoni L, Marchesi C, et al. Cost-effectiveness analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy. Farmeconomia. Health economics and therapeutic pathways 2016; 17: 67-80;
  • Kurtzke JF. A new scale for evaluating disability in multiple sclerosis. Neurology 1955; 5: 580-3
  • National Institute for Health and Care Excellence (NICE). Guide to the methods of technology appraisal 2013. Available at: (last accessed September 2018)
  • Gold R, Kappos L, Arnold DLet al. Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis. N Engl J Med 2012; 367: 1098-107;
  • 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;
  • 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
  • UK Multiple Sclerosis Survey. Patient demographics, regression model on EDSS, relapse, type of MS and other variables on utility derived from EQ-5D. 2007.
  • Weinshenker BG, Bass B, Rice GPA, et al. The Natural History Of Multiple Sclerosis: A Geographically Based Study. Brain 1989; 112: 133-46;
  • 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;
  • 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: 625-39
  • National Institute of Statistics of Italy (ISTAT). Mortality rates, 2018. Available at: (last accessed…)
  • Pokorski RJ. Long-term survival experience of patients with multiple sclerosis. J Insur Med 1997; 29: 101-6.
  • 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;
  • 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: 104-16;
  • 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;
  • National Institute of Statistics of Italy (ISTAT). Inflation rates. Available at: (last accessed September 2018)
  • De Angelis F, John NA, Brownlee WJ. Disease-modifying therapies for multiple sclerosis. BMJ 2018; 363: k4674;
  • Clinical expert opinion to determine monitoring costs associated to multiple sclerosis disease modifying therapies. Data on file. 2020
  • Garattini. Duration and costs of general practitioners’ visits: the DYSCO project. Farmeconomia e percorsi terapeutici 2003; 4: 109-14;
  • Italian Ministry of Health (2013). 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 (Report)
  • Italian Ministry of Health (2013). Inpatient intervention tariffs. Italian Republic Official Gazette. Chapter n. 23; Supplement n. 8; 28 January 2013.
  • Fattore G. Proposta di linee guida per la valutazione economica degli interventi sanitari in Italia. PharmacoEconomics - Italian Research Articles 2009; 11: 83-93
  • Lucioni C, Ravasio R. Come valutare i risultati di uno studio farmacoeconomico? Pharmaco Economics Italian Res Articles 2004; 6: 121-30
  • Messori A, Santarlasci B, Trippoli S, ET AL. Controvalore economico del farmaco e beneficio clinico: stato dell’arte della metodologia e applicazione di un algoritmo farmacoeconomico. PharmacoEconomics Ital Res Artic 2003; 5: 53-67;
  • Martone N, Lucioni C, Mazzi S, et al. Valutazione di costo-efficacia dei nuovi farmaci oncologici immessi sul mercato italiano. Glob Reg Heal Technol Assess 2014; 1: 31-43
  • Jönsson B. Changing health environment: the challenge to demonstrate cost-effectiveness of new compounds. Pharmacoeconomics 2004; 22: 5-10;
  • WHO, World Health Organization. Thresholds for the cost–effectiveness of interventions: alternative approaches. Available at: (last accessed February 2018)
  • Mantovani LG, Furneri G, Bitonti R, et al. Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective. Farmeconomia. Health economics and therapeutic pathways 2019; 20: 73-86;
  • Braune S, Grimm S, van Hövell P, et al. Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry. J Neurol 2018; 265: 2980-92;
  • Buron MD, Chalmer TA, Sellebjerg F, et al. Comparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort study. Neurology 2019; 92: e1811-20;


Abstract: 159 views
HTML: 25 views
PDF: 41 views


  • There are currently no refbacks.