Document Type : Original Article


1 Department of Pharmacoeconomics and Pharmaceutical Administration, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran


Background: The current study desired to conduct an economic analysis on ocrelizumab (OCR), a new relapsing multiple sclerosis (RMS) treatment strategy, in comparison to natalizumab (NTL), as one of the mostly-used disease-modifying therapies (DMTs) in Iran.
Methods: A 31-health-state Markov model, based on Expanded Disability Status Scale (EDSS), containing patients on- and off-treatment with annual cycles was developed. Baseline demographics and utility scores were extracted from OPERA 1 and 2 trials. Confirmed disability progression (CDP) and annualized relapse rates (ARR) were extracted from the literature. Mortality was calculated based on age, sex, and disease state. Quality-adjusted life years (QALYs) and life years gained (LYG) were measurements of efficacy. Direct and indirect costs were identified and calculated based on the national book of tariffs in Iranian Rial (IRR) rates, then converted to the 2020 United States Dollar (USD). Final results were reported in terms of incremental cost-effectiveness ratio (ICER), which showed extra costs required for one additional QALY. Robustness of the model was analyzed through deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA).
Results: OCR dominated NTL and was associated with cost-savings of 6971 USD, longer LYG (0.004), and higher QALYs (0.27). Although OCR had higher acquisition costs, which was the main component in both comparator arms, it was associated with lower total costs, due to lower disability progression and productivity loss. Results remained robust in DSA and PSA (93.5% cost-effectiveness in Iran’s pharmacoeconomic threshold, 2709 USD).
Conclusion: Results suggested that OCR was a more cost-effective option than NTL for the treatment of patients with RMS in Iran.


  1. Goldenberg MM. Multiple sclerosis review. P T 2012; 37(3): 175-84.
  2. Stenager E. A global perspective on the burden of multiple sclerosis. Lancet Neurol 2019; 18(3): 227-8.
  3. Cheong WL, Mohan D, Warren N, Reidpath DD. Multiple sclerosis in the Asia Pacific Region: A systematic review of a neglected neurological disease. Front Neurol 2018; 9: 432.
  4. Pittock SJ, McClelland RL, Mayr WT, Jorgensen NW, Weinshenker BG, Noseworthy J, et al. Clinical implications of benign multiple sclerosis: A 20-year population-based follow-up study. Ann Neurol 2004; 56(2): 303-6.
  5. Taheri S, Sahraian MA, Yousefi N. Cost-effectiveness of alemtuzumab and natalizumab for relapsing-remitting multiple sclerosis treatment in Iran: Decision analysis based on an indirect comparison. J Med Econ 2019; 22(1): 71-84.
  6. Naci H, Fleurence R, Birt J, Duhig A. Economic burden of multiple sclerosis: A systematic review of the literature. Pharmacoeconomics 2010; 28(5): 363-79.
  7. Torabipour A, Asl ZA, Majdinasab N, Ghasemzadeh R, Tabesh H, Arab M. A study on the direct and indirect costs of multiple sclerosis based on expanded disability status scale score in Khuzestan, Iran. Int J Prev Med 2014; 5(9): 1131-8.
  8. Etemadifar M, Izadi S, Nikseresht A, Sharifian M, Sahraian MA, Nasr Z. Estimated prevalence and incidence of multiple sclerosis in Iran. Eur Neurol 2014; 72(5-6): 370-4.
  9. Kurtzke JF. Multiple sclerosis in time and space--geographic clues to cause. J Neurovirol 2000; 6(Suppl 2): S134-S140.
  10. Khanizadeh H, Mohamed Ibrahim MI, Shafie A. PND12 the costs analysis of multiple sclerosis at different stages in Iran. Value Health 2012; 15(4): A143.
  11. Iran Food and Drug Administration. Iranian Drug List [Online]. [cited 2018]. Available from: URL:
  12. Yamout B, Alroughani R, Al-Jumah M, Goueider R, Dahdaleh M, Inshasi J, et al. Consensus recommendations for the diagnosis and treatment of multiple sclerosis: The Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS). Curr Med Res Opin 2015; 31(7): 1349-61.
  13. Syed YY. Ocrelizumab: A review in multiple sclerosis. CNS Drugs 2018; 32(9): 883-90.
  14. Abdoli G, Heydari H. An estimation of social discount rate based on hazard rate for Iran and selected countries. Iranian Economic Research 2009; 13(38): 1-29. [In Persian].
  15. Robberstad B. Estimation of private and social time preferences for health in northern Tanzania. Soc Sci Med 2005; 61(7): 1597-607.
  16. Meyer-Moock S, Feng YS, Maeurer M, Dippel FW, Kohlmann T. Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis. BMC Neurol 2014; 14: 58.
  17. Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med 2017; 376(3): 221-34.
  18. Palace J, Bregenzer T, Tremlett H, Oger J, Zhu F, Boggild M, et al. UK multiple sclerosis risk-sharing scheme: A new natural history dataset and an improved Markov model. BMJ Open 2014; 4(1): e004073.
  19. Orme M, Kerrigan J, Tyas D, Russell N, Nixon R. The effect of disease, functional status, and relapses on the utility of people with multiple sclerosis in the UK. Value Health 2007; 10(1): 54-60.
  20. 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(4): 248-66.
  21. Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, et al. The natural history of multiple sclerosis: A geographically based study 10: relapses and long-term disability. Brain 2010; 133(Pt 7): 1914-29.
  22. McCool R, Wilson K, Arber M, Fleetwood K, Toupin S, Thom H, et al. Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis. Mult Scler Relat Disord 2019; 29: 55-61.
  23. National Institute for Health and Care Excellence (NICE). Single Technology Appraisal Daclizumab for Treating Relapsing-Remitting Multiple Sclerosis [ID827]; [Online]. [cited 2016]; Available from: URL:
  24. National Institute for Health and Care Excellence (NICE). Alemtuzumab for Treating Relapsing-Remitting Multiple Sclerosis. [Online]. [cited 2013 Jul 5]; Available from: URL:
  25. National Institute for Health and Care Excellence (NICE). Natalizumab (Tysabri®) for the Treatment of Adults with Highly Active Relapsing Remitting Multiple
    Sclerosis [Online]. [cited 2007]; Available from: URL:
  26. National Institute for Health and Care Excellence (NICE). Technology appraisal TA217 Alzheimer's disease - donepezil, galantamine, rivastigmine and memantine [Online]. [cited 2009 Aug]; Available from: URL:
  27. Campbell JD, McQueen RB, Miravalle A, Corboy JR, Vollmer TL, Nair K. Comparative effectiveness of early natalizumab treatment in JC virus-negative relapsing-remitting multiple sclerosis. Am J Manag Care 2013; 19(4): 278-85.
  28. Orlewska E, Mierzejewski P, Zaborski J, Kruszewska J, Wicha W, Fryze W, et al. A prospective study of the financial costs of multiple sclerosis at different stages of the disease. Eur J Neurol 2005; 12(1): 31-9.
  29. Ministry of Health and Medical Education. Tariff of healthcare services in public and private sectors in Iran. Tehran, Iran: Ministry of Health and Medical Education Press; 2019. [In Persian].
  30. Pokorski RJ. Long-term survival experience of patients with multiple sclerosis. J Insur Med 1997; 29(2): 101-6.
  31. Frasco MA, Shih T, Incerti D, Diaz EO, Vania DK, Thomas N. Incremental net monetary benefit of ocrelizumab relative to subcutaneous interferon beta-1a. J Med Econ 2017; 20(10): 1074-82.
  32. Yang H, Duchesneau E, Foster R, Guerin A, Ma E, Thomas NP. Cost-effectiveness analysis of ocrelizumab versus subcutaneous interferon beta-1a for the treatment of relapsing multiple sclerosis. J Med Econ 2017; 20(10): 1056-65.
  33. National Institute for Health and Care Excellence (NICE). Appraisal consultation documentOcrelizumab for treating relapsing multiple sclerosis [Online]. [cited 2018]; Available from: URL:
  34. Canadian Agency for Drugs and Technologies in Health (CADTH). Pharmacoeconomic Review Report: Ocrelizumab (Ocrevus) (Hoffmann-La Roche Limited) Indication: Treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical and imaging features. Ottawa, ON: CADTH; 2017.
  35. Zimmermann M, Brouwer E, Tice JA, Seidner M, Loos AM, Liu S, et al. Disease-modifying therapies for relapsing-remitting and primary progressive multiple sclerosis: A cost-utility analysis. CNS Drugs 2018; 32(12): 1145-57.
  36. National Institute for Health and Care Excellence (NICE). Guide to the methods of technologyGuide to the methods of technologyapprappraisal 2013 [Online]. [cited 2013 Apr 4]; Available from: UR:
  37. Glennie JL, Torrance GW, Baladi JF, Berka C, Hubbard E, Menon D, et al. The revised Canadian Guidelines for the Economic Evaluation of Pharmaceuticals. Pharmacoeconomics 1999; 15(5): 459-68.