Cost-Effectiveness Analysis of Erenumab Versus OnabotulinumtoxinA for Patients with Chronic Migraine Attacks in Greece

  • Theodoros V. GiannouchosEmail author
  • Dimos-Dimitrios Mitsikostas
  • Robert L. Ohsfeldt
  • Athanassios Vozikis
  • Paraskevi Koufopoulou
Original Research Article



Migraine is a common, chronic neurovascular brain disorder with non-negligible multifaceted economic costs. Existing preventive treatments involve the selective use of onabotulinumtoxinA, which aims at migraine morbidity reduction for patients who have failed initial preventive treatment with oral agents. Erenumab is a new preventive treatment for migraines.


To evaluate the differences in costs and outcomes of the preventive treatment with erenumab versus onabotulinumtoxinA in patients with chronic migraines (CM) in Greece to assess the economic value of this treatment.


We conducted a cost-effectiveness analysis from both the payer and the societal perspective using a decision-tree analytic model. Outcomes were expressed in migraines avoided and in quality-adjusted life-years (QALYs). We obtained model inputs from the existing literature. The decision path adjusted for variation in the probability of adherence and the resulting differential effectiveness between the two treatments. Direct costs included the cost of the two drugs and administration costs, the costs of acute drugs used under usual care, and the costs of hospitalization, physician, and emergency department visits. Indirect costs for the societal perspective analyses included wages lost on workdays. The time-horizon of the analysis was 1 year and all costs were calculated in 2019 euros (€). Sensitivity analyses were conducted to control for parameter uncertainty and to evaluate the robustness of the findings.


Our results indicate that treatment of CM with erenumab compared to onabotulinumtoxinA resulted in incremental cost-effectiveness ratios (ICERs) of €218,870 and €231,554 per QALY gained and €620 and €656 per migraine avoided, from the societal and the payer’s perspective, respectively. Using a common cost-effectiveness threshold equal to three times the local gross domestic product (GDP) per capita (€49,000), for the erenumab ICERs to fall below this threshold, the erenumab price would have to be no more than €192 (societal perspective) or €173 (payer perspective).


The prophylactic treatment of CM with erenumab in Greece might be cost effective compared to the existing alternative of onabotulinumtoxinA from both the payer and the societal perspective, but only at a highly discounted price. Nevertheless, erenumab could be considered a therapeutic option for patients who fail treatment with onabotulinumtoxinA.



The authors would like to acknowledge Mr. Aristeidis Draganigos for his valuable input into the methodological part of this study.

Author Contributions

All authors contributed to the coordination of the study and drafting of the manuscript. TVG conceived and designed the study. TVG led the model development and performed the analyses. RLO and DDM contributed to the design and development of the model. DDM provided overall direction to the study. RLO, AV, and PK critically reviewed the analyses and assisted with the interpretation of the results. All authors reviewed and approved the final version of the manuscript for publication.

Compliance with Ethical Standards

Ethical standards

This study used data from existing published sources in a computational model. The research did not entail the use of data for any human subject at an individual level; thus institutional review board approval and informed consent were deemed unnecessary.


The authors did not receive any funding for this study.

Conflict of interest

The authors declare that they have no conflicts of interest. Other disclosures: DDM received honoraria for lecturing, consulting fees or research grants form Sanofi-Genzyme, Amgen, Allergan, Cefaly, Electrocore, Eli Lilly, Novartis, Merz, Merck-Serono, Roche, and Teva and has participated in clinical trials for agents analyzed in this study, which were however unrelated to this analysis.

Supplementary material

40261_2019_827_MOESM1_ESM.pdf (145 kb)
Supplementary material 1 (PDF 144 kb)


  1. 1.
    Leonardo M, Steiner T, Scher A. The global burden of migraine: Measuring disability in headache disorders with WHO’s Classification of Functioning, Disability and Health (ICF). J Headache Pain. 2005;6:429–40.CrossRefGoogle Scholar
  2. 2.
    Lipton RB, Stewart W, Diamond S, Diamond M, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646–57.CrossRefGoogle Scholar
  3. 3.
    Brandes JL. Global trends in migraine care: results from the MAZE survey. CNS Drugs. 2002;16:13–8.CrossRefGoogle Scholar
  4. 4.
    Mitsikostas D-D, Arvaniti C, Constantidis T, et al. A population based survey for headaches in Greece to estimate prevalence and treatment preferences. Neurology. 2018;90(P3):143.Google Scholar
  5. 5.
    Munakata J, Wang S, Rupnow M. Economic burden of transformed migraine: Results for the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2008;48:553–63.CrossRefGoogle Scholar
  6. 6.
    Messali A, Sanderson J, Blumenfeld AM. Direct and indirect costs of chronic and episodic migraine in the United States: a web-based survey. Headache. 2016;56:306–22.CrossRefGoogle Scholar
  7. 7.
    Serrano D, Manack AN, Reed ML, Buse DC, Varon SF, Lipton RB. Cost and predictors of lost productive time in chronic migraine and episodic migraine : results from the American Migraine Prevalence and Prevention (AMPP) Study. Value Health. 2013;16(1):31–8.CrossRefGoogle Scholar
  8. 8.
    Bonafede M, Sapra S, Shah N. Direct and indirect healthcare resource utilization and costs among migraine patients in the United States. Headache. 2018;58:700–15.CrossRefGoogle Scholar
  9. 9.
    D’Amico D, Grazzi L, Moschiano F, Bussone G. Topiramate in migraine prophylaxis. Neurol Sci. 2005;26:s130–3.CrossRefGoogle Scholar
  10. 10.
    Snow V, Weiss K, Wall E, Mottur-Pilson C. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137:840–9.CrossRefGoogle Scholar
  11. 11.
    Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS. EFNS guideline on the drug treatment of migraine–revised report of an EFNS task force. Eur J Neurol. 2009;16(9):968–81.CrossRefGoogle Scholar
  12. 12.
    Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754–63.Google Scholar
  13. 13.
    Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache. 2015;55(1):3–20.CrossRefGoogle Scholar
  14. 14.
    Silberstein SD, Holland S, Freitag F. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults: report of the quality standards subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337–45.CrossRefGoogle Scholar
  15. 15.
    Bagnato F, Good J. The use of antiepileptics in migraine prophylaxis. Headache. 2016;3:603–15.CrossRefGoogle Scholar
  16. 16.
    Yu J, Smith KJ, Brixner DI. Cost effectiveness of pharmacotherapy for the prevention of migraine. CNS Drugs. 2010;24(8):695–712.CrossRefGoogle Scholar
  17. 17.
    Diener HC, Dodick DW, Aurora SK, Turkel CC. OnabotulinumtoxinA for treatment of chronic migraine: results from placebo-controlled phase of the PREEMPT 2 trial. Cephalagia. 2010;30(7):804–14.CrossRefGoogle Scholar
  18. 18.
    Diener HC, Dodick DW, Turkel CC, Demos G, Degryse RE, Earl NL, Brin MF. Pooled analysis of the safety and tolerability of onabotulinumtoxinA in the treatment of chronic migraine. Eur J Neurol. 2014;21(6):851–9.CrossRefGoogle Scholar
  19. 19.
    Dodick DW, Turkel CC, Degryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT Clinical Program. Headache. 2010;50(6):921–36.CrossRefGoogle Scholar
  20. 20.
    Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary : botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache Academy of Neurology. Neurology. 2016;86(19):1818–26.CrossRefGoogle Scholar
  21. 21.
    Brown JS, Papadopoulos G, Neumann PJ, Price M, Friedman M, Menzin J. Cost-effectiveness of migraine prevention : the case of topiramate in the UK. Cephalalgia. 2006;26(12):1473–82.CrossRefGoogle Scholar
  22. 22.
    Silberstein SD, Lipton RB, Dodick D, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007;47(2):170–80.CrossRefGoogle Scholar
  23. 23.
    Brandes JL, Saper JR, Diamond M, et al. Topiramate for Migraine prevention. JAMA. 2004;291(8):965–73.CrossRefGoogle Scholar
  24. 24.
    Láinez MJ. The effect of migraine prophylaxis on migraine-related resource use and productivity. CNS Drugs. 2009;23(9):727–38.CrossRefGoogle Scholar
  25. 25.
    Silberstein S, Lipton R, Dodick D, et al. Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures. Headache. 2009;49(8):1153–62.CrossRefGoogle Scholar
  26. 26.
    Batty AJ, Hansen RN, Bloudek LM, et al. The cost-effectiveness of onabotulinumtoxinA for the prophylaxis of headache in adults with chronic migraine in the UK. J Med Econ. 2013;16(7):877–87.CrossRefGoogle Scholar
  27. 27.
    Vikelis M, Argyriou AA, Dermitzakis EV, Spingos KC, Mitsikostas DD. Onabotulinumtoxin-A treatment in Greek patients with chronic migraine. J Headache Pain. 2016;17(1):84.CrossRefGoogle Scholar
  28. 28.
    Lattanzi S, Brigo F, Trinka E, Vernieri F, Corradetti T, Dobran M, Silvestrini M. Erenumab for preventive treatment of migraine: a systematic review and meta-analysis of efficacy and safety. Drugs. 2019;79(4):417–31.CrossRefGoogle Scholar
  29. 29.
    Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies—successful translation from bench to clinic. Nat Rev Neurol. 2018;14(6):338–50.CrossRefGoogle Scholar
  30. 30.
    FDA Approves Aimovig (erenumab-aooe), a novel treatment developed specifically for migraine prevention. Amgen. Accessed Nov 2018.
  31. 31.
  32. 32.
    Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine : a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425–34.CrossRefGoogle Scholar
  33. 33.
    Lipton RB, Tepper SJ, Reuter U, Silberstein S, Stewart WF, Nilsen J, Leonardi DK, Desai P, Cheng S, Mikol DD, Lenz R. Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study. Neurology. 2019;92(19):e2250–60.CrossRefGoogle Scholar
  34. 34.
    Sussman M, Benner J, Neumann P, Menzin J. Cost-effectiveness analysis of erenumab for the preventive treatment of episodic and chronic migraine: results from the US societal and payer perspectives. Cephalalgia. 2018;38(10):1644–57.CrossRefGoogle Scholar
  35. 35.
    Brown JS, Papadopoulos G, Neumann PJ, Friedman M, Miller JD, Menzin J. Cost-effectiveness of topiramate in migraine prevention : results from a pharmacoeconomic model of topiramate treatment. Headache. 2005;45(8):1012–22.CrossRefGoogle Scholar
  36. 36.
    Landy SH, Runken MC, Bell CF, Higbie RL, Haskins LS. Assessing the impact of migraine onset on work productivity. J Occup Environ Med. 2011;53(1):74–81.CrossRefGoogle Scholar
  37. 37.
    Lipton RB, Brennan A, Palmer S, Hatswell AJ, Porter JK, Sapra S, Villa G, Shah N, Tepper S, Dodick D. Estimating the clinical effectiveness and value-based price range of erenumab for the prevention of migraine in patients with prior treatment failures: a US societal perspective. J Med Econ. 2018;21(7):666–75.CrossRefGoogle Scholar
  38. 38.
    Caro G, Getsios D, Caro J. Sumatriptan: economic evidence for its use in the treatment of migraine, the Canadian economic analysis. Cephalalgia. 2001;21:12–9.CrossRefGoogle Scholar
  39. 39.
    Caro J, Caro G, Getsios D. The migraine ACE model: evaluating the impact on time lost and medical resource use. Headache. 2000;42:282–91.CrossRefGoogle Scholar
  40. 40. Accessed Feb 2019.
  41. 41.
    Foundation for Economic and Industrial Research (IOBE). Rationalization of Pharmaceutical Pricing System in Greece. Athens: Foundation for Economic and Industrial Research (IOBE) (2013).Google Scholar
  42. 42.
  43. 43.
    Institute for Clinical and Economic Review (ICER). Calcitonin Gene-Related Peptide (CGRP) Inhibitors as Preventive Treatments for Patients with Episodic or Chronic Migraines: Effectiveness and Value. Final Evidence Report. July 3, 2018.Google Scholar
  44. 44.
    Marseille E, Larson B, Kazi DS, Kahn JG, Rosen S. Thresholds for the cost–effectiveness of interventions: alternative approaches. Bull World Health Organ. 2014;93:118–24.CrossRefGoogle Scholar
  45. 45.
    Fendrick AM, Smith DG, Chernew ME, Shah SN. A benefit-based copay for prescription drugs: patient contribution based on total benefits, not drug acquisition cost. Am J Manag Care. 2001;7(9):861–74.Google Scholar
  46. 46.
    Giannouchos T. Comparative Analysis of Pharmaceutical Expenditure in Greece and the countries of the Eurozone the years 2005–2016 (in Greek). 2016. Accessed Dec 2018.
  47. 47.
    Campbell EG, Gruen RL, Mountford J, Miller LG, Cleary PD, Blumenthal D. A national survey of physician-industry relationships. N Engl J Med. 2007;356(17):1742–50.CrossRefGoogle Scholar
  48. 48.
    Stevenson FA, Greenfield SM, Jones M, Nayak A, Bradley CP. GPs’ perceptions of patient influence on prescribing. Fam Pract. 1999;16(3):255–61.CrossRefGoogle Scholar
  49. 49.
    Horodnic AV, Williams CC, Polese A, Zait A, Oprea L. Exploring the practice of making informal payments in the health sector: some lessons from Greece. In: The informal economy in global perspective 2017. Cham: Palgrave Macmillan; 2017. p. 157–72.Google Scholar
  50. 50.
    Lewis M. Informal payments and the financing of health care in developing and transition countries. Health Aff. 2007;26(4):984–97.CrossRefGoogle Scholar
  51. 51.
    Charles C, Whelan T, Gafni A. What do we mean by partnership in making decisions about treatment? BMJ. 1999;319(7212):780–2.CrossRefGoogle Scholar
  52. 52.
    Mathew PG, Pavlovic JM, Lettich A, Wells RE, Robertson CE, Mullin K, Charleston L IV, Dodick DW, Schwedt TJ. Education and decision making at the time of Triptan prescribing: patient expectations vs actual practice. Headache. 2014;54(4):698–708.CrossRefGoogle Scholar
  53. 53.
    Payne KA, Varon SF, Kawata AK, Yeomans K, Wilcox TK, Manack A, Buse DC, Lipton RB, Goadsby PJ, Blumenfeld AM. The International Burden of Migraine Study (IBMS): study design, methodology, and baseline cohort characteristics. Cephalalgia. 2011;31(10):1116–30.CrossRefGoogle Scholar
  54. 54.
    Shiroiwa T, Fukuda T, Ikeda S, Shimozuma K. QALY and productivity loss: empirical evidence for “double counting”. Value Health. 2013;16(4):581–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Health Policy and Management, School of Public HealthTexas A&M UniversityCollege StationUSA
  2. 2.Population Informatics LabTexas A&M UniversityCollege StationUSA
  3. 3.First Neurology Department, Aeginition Hospital, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  4. 4.Laboratory of Health Economics and Management, Economics DepartmentUniversity of PiraeusPireasGreece
  5. 5.KAT General Hospital of AtticaKifisiaGreece

Personalised recommendations