Pharmacoeconomic analysis of Xeomine® for treatment patients with focal dystonia

Focal dystonia is a large group of diverse neurological syndromes characterized by significant muscular contractions, spasms, repetitive movements, and persistent pathological poses (which in turn often causes pain syndrome). Blepharospasm (BSP) and cervical dystonia (CD) are two focal dystonias that have a particularly strong impact upon patient’s quality of life (QoL) and work performance. The most effective treatment for these syndromes is injection of botulinum toxin into the affected muscles. Currently there are three notable botulinum toxin drugs on the market - onabotulinumtoxinA (Botox®), incobotulinumtoxinA (Xeomin®), abobotulinumtoxinA (Dysport®). Their notable similarity in terms of safety and effectiveness, as well as severity of impact BSP and CD have on patient’s QoL confer considerable importance to performing proper pharmacoeconomic assessment of the relative benefits of these drugs, which is the subject of current effort. Aim. To perform the pharmacoeconomic analysis (PHe) of therapy using onabotulinumtoxinA, incobotulinumtoxinA, abobotulinumtoxinA of patients suffering from BSP or CD within context of Russian healthcare. Methodology. This PHe research effort is conducted perspective of Russian Healthcare system, as well as generalized budgetary interest (including GDP impact of the disease). The time horizon for this research was 5 years. Comparator drugs were Xeomin®, Dysport®, Botox®. Randomized controlled clinical trials investigating safety and efficacy of these were used as data source on safety and efficacy. Each simulated cohort consisted of 1 000 patients. A complex PHe model consisting of a “decision tree” (break cohorts down into subgroups depending on estimated duration of therapeutic effect) was developed. The subgroups were then directed into a Markov model for evaluating treatment outcomes proper was constructed. Cycle length for the Markov component of the model was set at 1 week. Length of time patients spend in state of clinical remission was chosen as effectiveness criterion because this endpoint is both most clinically relevant and constitutes the main social impact of investigated medical intervention. The results of this modelling effort were used to perform cost-minimization analysis (CMA), budget impact analysis (BIA). Result stability was confirmed by performing sensitivity analysis (SA). Result. Reduction in direct costs by 1 patient on average over 1 year of therapy using Xeomin® has been 26,5% and 19,7% compare Botox® and Dysport® respectively. Xeomin® has demonstrated significant benefit during CMA for both indications (CD and BSP), dominating against Botox® (the savings over 5 years by 1 patient 123 180 rub. (9,7%) and 64 107 rub. (6,1%), respectively) and against Dysport® (84 019 rub. (6,8%) and 43 726 rub. (4,2%), respectively). SA confirms result robustness. To perform BIA a complex analytical scenario was constructed. Within that scenario, market fraction of Dysport® was reduced gradually over the course of 2 years and the patients discontinuing Dysport® were moved to Xeomin® (ratio 3:1). This scenario has indicated that a move to Xeomin® is associated with reduction in budgetary burden, with most significant budget economy happening when patients suffering from CD are moved to Xeomin® (according to BIA the savings from moving to Xeomin® constituted 1,37% thus exceeding 71 million rub.). Conclusion. Use of Xeomin® is associated with reduction in direct costs for Russian healthcare system. Analysis indicates that discontinuing Dysport® in favor of Xeomine within context of governmental healthcare would result in reduction of budgetary burden. These results suggest that Xeomine® is highly pharmacoeconomically expedient within context of Russian healthcare system.

блефароспазм, цервикальная дистония, ботулотоксин, Ксеомин, Диспорт, Ботокс, фармакоэкономика, анализ минимизации затрат, анализ влияния на бюджет, blepharospasm, cervical dystonia, botulinum toxin, Xeomine, Dysport, Botox, pharmacoeconomics, cost-minimization analysis, budget impact analysis

1. Аналитическая информация, IMS Россия, 2015 г. [Электронный ресурс] URL: http://www.imshealth.com/ (дата обращения: 21.06.2016).

2. Артеменко А.Р., Куренков А.Л. Ботулинический токсин: вчера, сегодня, завтра. Нервно-мышечные болезни. - 2013. - № 2. - С. 6-18.

3. Белоусов Ю.Б., Белоусов Д.Ю. Учебное пособие «Основы фармакоэкономических исследований», М., 2000 г. Национальный фонд содействия научным и клиническим исследованиям при РГМУ

4. Государственный реестр предельных отпускных цен. [Электронный ресурс] http://grls.rosminzdrav.ru/pricelims.aspx (дата обращения: 08.04.2016).

5. Информационный сервис «aptekamos.ru» [Электронный ресурс] URL: http://aptekamos.ru/apteka/ (дата обращения: 08.04.2016).

6. Логинова Н.В., Каракулова Ю.В. Коморбидность болевого синдрома и эмоциональных расстройств у пациентов со спастической кривошеей. Современные проблемы науки и образования. 2015; 6. [Электронный ресурс] URL: http://www.science-education.ru/ru/article/view?id=23088 (дата обращения: 11.06.2016).

7. Орлова О.Р. Фокальные дистонии: диагностика и современная терапия с применением ботулинического токсина типа А (по материалам Европейского консенсуса и Российских клинических рекомендаций) гл в кн. Гусев Е.И., Гехт А.Б. Болезни мозга - медицинские и социальные аспекты. М.: ООО «Буки-Веди», 2016; 768 (553-568).

8. Отраслевой стандарт «Клинико-экономические исследования. Общие положения» Приказ Минздрава РФ от 27.05.2002 г. № 163 вместе с ОСТ 91500.14.0001-2002.

9. Приказ Министерства труда и социальной защиты РФ от 17.12.2015 N 1024н «О классификациях и критериях, используемых при осуществлении медико-социальной экспертизы граждан федеральными государственными учреждениями медико-социальной экспертизы».

10. Сайт Государственного реестра лекарственных средств. [Электронный ресурс] URL: http://grls.rosminzdrav.ru (дата обращения: 02.06.2016).

11. Стандарт специализированной медицинской помощи при дистониях. Утверждён приказом МЗ РФ № 1540н от 24.12.2012 г.

12. Тарифы на медицинские услуги Московского городского фонда ОМС, введённые в действие в 2015 г. [Электронный ресурс] URL: http://www.mgfoms.ru.

13. Тимербаева С.Л. Фокальные и сегментарные формы первичной дистонии: клинические, патофизиологические и молекулярно-генетические аспекты. Автореф. докт. дисс. 2012; 51.

14. Тимербаева С.Л. Азбука ботулинотерапии: научно-практическое издание. М.: Практическая медицина, 2014; 416.

15. Тимербаева С.Л. Неэффективность ботулинотерапии: старая проблема, новые решения. Атмосфера. Нервные болезни. 2015; 4: 28-32.

16. Федеральная служба государственной статистики, 2015 г. [Электронный ресурс] URL: http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/ statistics/accounts/# (дата обращения: 02.06.2016).

17. Федеральная служба государственной статистики, 2015 г. Численность и состав населения в 2015 г. [Электронный ресурс] URL: http://www.gks.ru/wps/ wcm/connect/rosstat_main/rosstat/ru/statistics/population/demography/# (дата обращения: 11.06.2016).

18. Федеральный закон от 29.12.2006 N 255-ФЗ (действующая редакция, 2016) « Об обязательном социальном страховании на случай временной нетрудоспособности и в связи с материнством».

19. Ягудина Р.И., Куликов А.Ю., Крысанов И.С., Литвиненко М.М., Морозов А.Л. Особенности методологии фармакоэкономических исследований в условиях здравоохранения Российской Федерации (обзор публикаций за период с 1995 по 2007 гг.). Фармакоэкономика. 2009; 1: 3-6.

20. Яхно Н.Н., Штульман Д.Р. Болезни нервной системы: Руководство для врачей: в 2-х т. - Т. 2- 2-е изд., перераб и доп. М.: Медицина, 2001; 480.

21. Albanese A., Bhatia K., Bressman S.B. et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013; 28: 863-873.

22. Albanesel A., Abbruzzese G., Dressler D. et al. Practical guidance for CD management involving treatment of botulinum toxin: a consensus statement. J Neurol. 2015; 262: 2201-2213.

23. Comella C.L., Jankovic J., Truong D.D. et al. Efficacy and safety of incobotulinumtoxinA (NT 201, XEOMIN, botulinum neurotoxin type A, without accessory proteins) in patients with cervical dystonia. J Neurol Sci. 2011; 308: 103-109.

24. Dashtipour K., Chen J.J., Espay A.J. et al. OnabotulinumtoxinA and AbobotulinumtoxinA dose conversion: a systematic literature review. Movement Disorders Clinical Practice 2015. Published online 12 October 2015 in Wiley InterScience (www.interscience.wiley.com). Doi:10.1002/mdc3.12235.

25. Dressler D., Mander G., Fink K. Measuring the potency labelling of onabotulinumtoxin A (Botoxe) and incobotulinumtoxin A (Xeomin®1 in an LD50 assay. J Neural Transm. 2012; 119:13-15.

26. Evidente V.G., Fernandez H.H., LeDoux M.S. et al. A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia. J Neural Transm. 2013; 120 (12): 1699-1707.

27. Fraint A., Vittal P., Comella C. Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe? Therapetics and Clinical Risk Management. 2016; 12: 147-154.

28. Grosset D.G., Tyrrell E.G., Grosset K.A. Switch from abobotulinumtoxinA (Dysport) to incobotulinumtoxina (Xeomin) botulinum toxin formulation: a review of 257 cases. J Rehabil Med. 2005; 47: 183-186.

29. Hilker R., Schischniaschvili M., Ghaemi M., Jacobs A., Rudolf J. Health related quality of life is improved by botulinum neurotoxin type A in long term treated patients with focal dystonia. J Neurol Neurosurg Psychiatry. 2001; 71 (2): 193-199.

30. Jankovic J. Clinical efficacy and tolerability of xeomin in the treatment of blepharospasm. Eur J Neurol. 2009; 16 (Suppl. 2): 14-18.

31. Jost W. Pictorial Atlas of botulinum toxin injection. Dosage. Localization. Application. First English Edition. Quintessence Book, 2008. 264.

32. Lange O., Bigalke H., Dengler R. et al. Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: much ado about nothing? Clin Neuropharmacol. 2009; 32: 213-218.

33. Marchetti A., Magar R., Findley L. et al. Retrospective evaluation of the dose of Dysport and BOTOX in the management of cervical dystonia and blepharospasm: The REAL DOSE study. Mov Disord 2005;20:937-944.

34. Reichel G. Therapieleitfaden Spastik - Dystonien. 3. Auflage. Bremen: UNI-MED, 2006; 188.

35. Ranoux D., Gury C., Fondarai J. et al. Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. JNNP. 2002; 72 (4): 459-62.

36. Scaglione F. Conversion ratio between Botox®, Dysport®, and Xeomin® in clinical practice. Toxins 2016;8(3):65.

37. Schwartz R. Biological modeling and simulation: a survey of practical models, algorithms and numerical methods. The MIT Press, 2008.

38. Sethi K.D., Rodriguez R., Olayinka B. Satisfaction with botulinum toxin treatment: a cross-sectional survey of patients with cervical dystonia. Jornal of Medical Economics. 2012; 15 (3): 419-423.

39. Simpson D.M., Hallett M., Ashman E.J. et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. Neurology. 2016; 86: 1818-1826.

40. Stacy M. Handbook of Dystonia. Second Edition. Informa healthcare. 2012; 540.

41. Truong D., Dressler D., Hallett M. Manual of Botulinum Toxin Therapy. Cambridge University Press, 2009. 218 p.

42. Truong D.D., Gollomp S.M., Jankovic J. et al. Xeomin US Blepharospasm Study Group Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin(®)) injections in blepharospasm. J Neural Transm. 2013; 120 (9): 1345-1353.