idiopathic thrompocytopenic purpura

Pharmacoeconomic Analysis of the Use of Thrombopoietin Receptors Agonists in Idiopathic Thrombocytopenic Purpura Therapy

PHARMACOECONOMICS ,

VA Shuvaev1, SV Voloshin1, AK Hadzhidis2, AV Chechetkin1

1Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2Saint Petersburg State Pediatric Medical University, 2 Litovskaya str., Saint Petersburg, Russian Federation, 194100

For correspondence: Vasilii Anatol’evich Shuvaev, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; e-mail: shuvaev77@mail.ru

For citation: Shuvaev VA, Voloshin SV, Khadzhidis AK, Chechetkin AV. Pharmacoeconomic Analysis of the Use of Thrombopoietin Receptors Agonists in Idiopathic Thrombocytopenic Purpura Therapy. Clinical oncohematology. 2017;10(4):435–42 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-435-442

ABSTRACT

Background. New medications, thrombopoietin mimetics which were recently introduced into clinical practice allowed to achieve clinical response in patients with chronic glucocorticoid-resistant idiopathic thrombocytopenic purpura (ITP). However, the high cost and the need for long-term administration necessitate a pharmacoeconomic analysis of the use of thrombopoietin receptors agonists in the treatment of ITP.

Aim. To assess the cost-effectiveness of the use of thrombopoietin mimetics (romiplostim and eltrombopag) and immunosuppressive therapy in the treatment of chronic glucocorticoid-resistant ITP.

Materials & Methods. The Markov modelling of diagnosis and treatment of ITP was conducted in accordance with the National guidelines for diagnosis and treatment of primary ITP. The cost-benefit analysis of the use of thrombopoietin receptors agonists (romiplostim and eltrombopag) and immunosuppressive therapy was performed. The time period (horizon) of the study was 5 years.

Results. The therapy with thrombopoietin mimetics had higher costs but was shown to be more effective compared to immunosuppressive therapy. The cost-effectiveness for achieving 1 QALY in the treatment was 1.33 million rubles with eltrombopag, 4.2 million rubles with romiplostim, and 0.17 million rubles with immunosuppressive therapy. The lowest additional costs compared to immunosuppressive therapy had eltrombopag treatment, whereas romiplostim treatment doubled the additional costs. The threshold values of the ratio of thrombopoietin receptors agonists costs were determined for the cost-benefit analysis. The use of romiplostim is cost-effective at a price for 1 vial of 15–18 % less than for 1 package of eltrombopag. The total cumulative burden of treatment of chronic ITP for 5 years may be 7.18 billion rubles with the use of eltrombopag, 23.23 billion rubles with romiplostim, and 0.91 billion rubles with immunosuppressive therapy only. The results confirm the need for budgeting the diagnosis and treatment of ITP not as a part of general approach, but to consider ITP as an orphan disease.

Conclusion. The developed pharmacoeconomic model can be used as an assessment tool of the costs of new diagnostic approaches and treatment strategies and optimizing budget expenditures.

Keywords: idiopathic thrombocytopenic purpura, romiplostim, eltrombopag, cost-effectiveness.

Received: May 15, 2017

Accepted: August 7, 2017

Read in PDF

REFERENCES

  1. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168–86. doi: 10.1182/blood-2009-06-225565.
  2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an International Working Group. Blood. 2009;113(11):2386–93. doi: 10.1182/blood-2008-07-162503.
  3. Меликян А.Л., Пустовая Е.И., Цветаева Н.В. и др. Национальные клинические рекомендации по диагностике и лечению первичной иммунной тромбоцитопении (идиопатической тромбоцитопенической пурпуры) у взрослых. Гематология и трансфузиология. 2015;60(1):44–56.Melikyan AL, Pustovaya EI, Tsvetaeva NV, et al. National clinical guidelines for еру diagnosis and treatment of primary immune thrombocytopenia (idiopathic thrombocytopenic purpura) in adult patients. Gematologiya i transfuziologiya. 2015;60(1):44–56. (In Russ)]
  4. Лисуков И.А., Масчан А.А., Шамардина А.В. и др. Иммунная тромбоцитопения: клинические проявления и ответ на терапию. Промежуточный анализ данных Российского регистра пациентов с первичной иммунной тромбоцитопенией и обзор литературы. Онкогематология. 2013;8(2);61–9. doi: 10.17650/1818-8346-2013-8-2-61-69.[Lisukov IA, Maschan AA, Shamardina AV, et al. Immune thrombocytopenia: clinical manifestation and therapy response. The interim analysis of Russian register of patients with primary immune thrombocytopenia and literature review. Onkogematologiya. 2013;8(2);61–9. doi: 10.17650/1818-8346-2013-8-2-61-69. (In Russ)]
  5. Rodeghiero F, Michel M, Gernsheimer T, et al. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013;121(14):2596–606. doi: 10.1182/blood-2012-07-442392.
  6. Масчан А.А., Румянцев А.Г. Стимуляция продукции тромбоцитов: новый подход к лечению хронической иммунной тромбоцитопенической пурпуры. Онкогематология. 2009:1:51–6.[Maschan AA, Rumyantsev AG. Stimulation of platelet production: The new treatment approach to chronic immune thrombocytopenic purpura. Onkogematologiya. 2009:1:51–6. (In Russ)]
  7. Kuter DJ, Bussel JB, Newland A, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161(3):411–23. doi: 10.1111/bjh.12260.
  8. Garnock-Jones KP, Keam SJ. Eltrombopag. Drugs. 2009;69(5):567–76. doi: 10.2165/00003495-200969050-00005.
  9. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the Treatment of Chronic Idiopathic Thrombocytopenic Purpura. N Engl J Med. 2007;357(22):2237–47. doi: 10.1056/NEJMoa073275.
  10. Меликян А.Л., Пустовая Е.И., Цветаева Н.В. Национальные клинические рекомендации по диагностике и лечению первичной иммунной тромбоцитопении (идиопатической тромбоцитопенической пурпуры) у взрослых [электронный документ]. Доступно по: http://npngo.ru/wp-content/uploads/2016/09/nacionalnye-klinicheskie-rekomendacii-po-diagnostike-i-lecheniyu-idiopaticheskoj-trombocitopenicheskoj-purpury-pervichnoj-immunnoj-trombocitopenii-u-vzroslyx.pdf. Ссылка активна на 31.07.2017.[Melikyan AL, Pustovaya EI, Tsvetaeva NV, et al. National clinical guidelines for diagnosis and treatment of primary immune thrombocytopenia (idiopathic thrombocytopenic puprura) in adult patients [Internet]. Available from: http://npngo.ru/wp-content/uploads/2016/09/nacionalnye-klinicheskie-rekomendacii-po-diagnostike-i-lecheniyu-idiopaticheskoj-trombocitopenicheskoj-purpury-pervichnoj-immunnoj-trombocitopenii-u-vzroslyx.pdf. (accessed 31.07.2017) (In Russ)]
  11. Воробьев А.П. Клинико-экономический анализ. М.: Ньюдиамед, 2008. 778 с.[Vorob’ev AP. Kliniko-ekonomicheskii analiz. (Clinico-economic analysis.) Moscow: N’yudiamed Publ.; 2008. 778 p. (In Russ)]
  12. Федеральная служба государственной статистики [электронный документ]. Доступно по: http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/accounts/#. Ссылка активна на 31.07.2017.[Federal Service of State statistics [Internet]. Available from: http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/accounts/#. (accessed 31.07.2017) (In Russ)]
  13. Ковалева Л.Г., Сафонова Т.И., Колосова Е.Н. и др. Клинико-статистические данные и оценка различных методов терапии идиопатической тромбоцитопенической пурпуры. Терапевтический архив. 2011;4:60–5.[Kovaleva LG, Safonova TI, Kolosova EN, et al. Clinical statistics and effectiveness of different treatments of idiopathic thrombocytopenic purpura. Terapevticheskii arkhiv. 2011;4:60–5. (In Russ)]
  14. Szende A, Brazier J, Schaefer C, et al. Measurement of utility values in the UK for health states related to immune thrombocytopenic purpura. Curr Med Res Opin. 2010;26(8):1893–903. doi: 10.1185/03007995.2010.494126.
  15. Sanz MA, Aledort L, Mathias SD, et al. Analysis of EQ-5D scores from two phase 3 clinical trials of romiplostim in the treatment of immune thrombocytopenia (ITP). Value in Health. 2011;14(1):90–6. doi: 10.1016/j.jval.2010.10.017.
  16. National Institute for Health and Care Excellence. Romiplostim for the treatment of chronic immune (idiopathic) thrombocytopenic purpura. NICE technology appraisal guidance [TA221] 27.04.2011 [cited 2014 May 1]. Available from: https://www.nice.org.uk/guidance/ta221. Accessed 31.07.2017.
  17. Boyers D, Jia X, Jenkinson D, et al. Eltrombopag for the Treatment of Chronic Immune or Idiopathic Thrombocytopenic Purpura. PharmacoEconomics. 2012;30(6):483–95. doi: 10.2165/11591550-000000000-00000.
  18. Официальный сайт единой информационной системы в сфере закупок [электронный документ]. Доступно по: . Ссылка активна на 31.07.2017.[Official website of the United information system of state purchases [Internet]. Available from: . (accessed 31.07.2017) (In Russ)]
  19. Жулев Ю. У закона нет сирот. Российская газета: Фармацевтика. 2012;5717(44) [электронный документ]. Доступно по: https://rg.ru/2012/03/01/zakon.html. Ссылка активна на 31.07.2017.[Zhulev Y. The law has no orphans. Rossiiskaya gazeta: Farmatsevtika. 2012;5717(44) [Internet]. Available from: https://rg.ru/2012/03/01/zakon.html. (accessed 31.07.2017) (In Russ)]
  20. National Institute for Health and Care Excellence. Eltrombopag for treating chronic immune (idiopathic) thrombocytopenic purpura. NICE technology appraisal guidance [TA293] 24.07.2013 [cited 2016 Sep 3]. Available from: https://www.nice.org.uk/guidance/ta293. Accessed 31.07.2017.

Thrombopoietin Receptor Agonists in Treatment of Idiopathic Thrompocytopenic Purpura (Primary Immune Thrombocytopenia): Efficacy and Safety in Everyday Clinical Practice

IMMUNE THROMBOCYTOPENIAS ,

II Zotova, SV Gritsaev, ER Shilova, NA Potikhonova, KМ Abdulkadyrov, AV Chechetkin

Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Irina Ivanovna Zotova, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel: +7(812)271-44-31; e-mail: hemzot@mail.ru

For citation: Zotova II, Gritsaev SV, Shilova ER, et al. Thrombopoietin Receptor Agonists in Treatment of Idiopathic Thrompocytopenic Purpura (Primary Immune Thrombocytopenia): Efficacy and Safety in Everyday Clinical Practice. Clinical oncohematology. 2017;10(1):93–100 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-93-100

ABSTRACT

Background & Aims. The use of thrombopoietin receptor agonists (aTPO-r) is a new approach to the treatment of patients with idiopathic thrompocytopenic purpura (ITP) irresponsive to other methods. Data on the efficacy and safety of aTPO-r outside the frames of clinical trials are limited. The aim of the study is to evaluate the efficacy of the therapy in the routine clinical practice as the second and subsequent lines of therapy, as well as the frequency and nature of complications of the treatment in chronic ITP patients.

Methods. Data on 58 adult patients (median age: 56 years) with chronic ITP were retrospectively evaluated; 43 (74 %) of them were treated with romiplostim and 15 (26 %) patients received eltrombopag. Two or more lines of prior therapy were ineffective in 19 (33 %) patients (14 from the romiplostim group and 5 from the eltrombopag group). aTPO-r was prescribed and adjusted according to the prescription guidelines. The efficacy of the treatment was assessed based on the platelet response and the possibility of achieving a sustained response after discontinuation of the therapy. Hemorrhagic manifestations were classified according to the WHO bleeding scale. The safety assessment is conducted by identifying adverse events (AEs) and lab test abnormalities. Treatment-related adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

Results. The therapy with aTPO-r was effective in 49 (84 %) patients, including 36 patients (84 %) treated with romiplostim and 13 patients (87 %) with eltrombopag. The median dose to maintain a response was 3.7 mg/kg and 44 mg, respectively. A stable remission was achieved in 4 patients after discontinuation of romiplostim and 1 patient after discontinuation of eltrombopag. aTPO-r resistance was diagnosed in 9 (16 %) patients: 7 (16 %) of them were from the romiplostim group and 2 (13 %) from the eltrombopag group. Complete arrest of bleeding was achieved in 43 (88 %) responders and its reduction to grade I was achieved in the remaining 6 (12 %) of them. The most frequent AEs of romiplostim therapy were headache, arthralgia and dermatitis; and the treatment with eltrombopag caused hepatotoxicity, headache, and nausea. The severity of events did not lead to complete discontinuation of the therapy in any case. Different types of thrombotic complications were diagnosed in 3 patients (5.2 %).

Conclusion. The therapy with aTPO-r is an effective and safe method for the treatment of patients with chronic ITP in the second and subsequent lines of therapy.

Keywords: immune thrombocytopenia, idiopathic thrompocytopenic purpura, romiplostim, eltrombopag.

Received: July 27, 2016

Accepted: November 25, 2016

Read in PDF (RUS)pdficon

REFERENCES

  1. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168–86. doi: 10.1182/blood-2009-06-225565.
  2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standartization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386–93. doi: 10.1182/blood-2008-07-162503.
  3. Масчан А.А., Румянцев А.Г., Ковалева Л.Г. и др. Рекомендации российского совета экспертов по диагностике и лечению больных первичной иммунной тромбоцитопенией. Онкогематология. 2010;3:36–45.
    [Maschan AA, Rumyantsev AG, Kovaleva LG, et al. Guidelines of Russian expert council on diagnostic and therapy of patients with primary immune thrombocytopenia. Onkogematologiya. 2010;3:36–45. (In Russ)]
  4. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–207. doi: 10.1182/blood-2010-08-302984.
  5. Меликян А.Л., Пустовая Е.И., Цветаева Н.В. и др. Национальные клинические рекомендации по диагностике и лечению первичной иммунной тромбоцитопении (идиопатической тромбоцитопенической пурпуры) у взрослых. Гематология и трансфузиология. 2015;60(1):44–56.
    [Melikyan AL, Pustovaya EI, Tsvetaeva NV, et al. National clinical recommendations for diagnosis and therapy of idiopathic thrombocytopenic purpura (primary immune thrombocytopenia) in adults. Gematologiya i transfuziologiya. 2015;60(1):44–56. (In Russ)]
  6. Ковалева Л.Г., Сафонова Т.И., Пустовая Е.И. и др. Клинико-статистические данные и оценка различных методов терапии идиопатической тромбоцитопенической пурпуры. Терапевтический архив. 2011;4:60–5.
    [Kovaleva LG, Safonova TI, Pustovaya EI, et al. Clinical statistic data and evaluation of different methods of treatment of idiopathic thrombocytopenic purpura. Terapevticheskii arkhiv. 2011;4:60–5. (In Russ)]
  7. Kuter DJ. Milestones in understanding platelet production: a historical overview. Br J Haematol. 2014;165(2):248–58. doi: 10.1111/bjh.12781.
  8. Stasi R, Evangelista ML, Stipa E, et al. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost. 2008;99(1):4–13. doi: 10.1160/Th07-08-0513.
  9. Nurden AT, Viallard JF, Nurden P, et al. New generation drags that stimulate platelet production in chronic immune thrombocytopenic purpura. Lancet. 2009;373(9674):1562–9. doi: 10.1016/S0140-6736(09)60255-5.
  10. Bussel JB, Kuter DJ, George JN, et al. AMG 531, a thrombopoietin stimulating protein, for chronic ITP. N Engl J Med. 2006;355(16):1672–81. doi: 10.1056/NEJMoa054626.
  11. Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic immune thrombocytopenic purpura: a randomised double-blind, placebo-controlled trial. Lancet. 2009;373(9664):641–8. doi: 10.1016/S0140-6736(09)60402-5.
  12. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371(9610):395–403. doi: 10.1016/S0140-6736(08)60203-2.
  13. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomized, phase 3 study. Lancet. 2011;377(9763):393–402. doi: 10.1016/S0140-6736(10)60959-2.
  14. Kuter DJ, Bussel JB, Newland AC, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161(3):411–23. doi: 10.1111/bjh.122260.
  15. Saleh MN, Bussel JB, Cheng G, et al. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013;121(3):537–45. doi: 10.1182/blood-2012-04-425512.
  16. Bussel JB, Rodeghiero F, Lyons R, et al. Sustained hemostatic platelet counts in adults with chronic immune thrombocytopenia (ITP) following cessation of treatment with the TPO receptor agonist romiplostim: report of 9 cases. Blood (ASH Annual Meeting Abstracts). 2011;118(21): Abstract 3281.
  17. Carpendo M, Cantoni S, Coccini V. et al. Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice. Hematol Rep. 2015;7(1):5673. doi: 10.4081/hr.2015.5673.
  18. Mahevas M, Fain O, Ebbo M, et al. The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Hematol. 2014;165(6):865–9. doi: 10.1111/bjh.12888.
  19. Khellaf M, Michel M, Quittet P, et al. Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program. Blood. 2011;118(16):4338–45. doi: 10.1182/blood-2011-03-340166.
  20. Лисуков И.А., Масчан А.А., Шамардина А.В. и др. Иммунная тромбоцитопения: клинические проявления и ответ на терапию. Промежуточный анализ данных Российского регистра пациентов с первичной иммунной тромбоцитопенией и обзор литературы. Онкогематология. 2013;2:61–9.
    [Lisukov IA, Maschan AA, Shamardina AV, et al. Immune thrombocytopenia: clinical manifestation and therapy response. The interim analysis of data from Russian registry of patients with primary immune thrombocytopenia and literature review. Onkogematologiya. 2013;2:61–9. (In Russ)]
  21. Птушкин В.В., Миненко С.В., Биячуев Э.Р. и др. Лечение больных с резистентной иммунной тромбоцитопенией: обзор литературы и клинические наблюдения. Онкогематология. 2011;1:56–63. doi: 10.17650/1818-8346-2011-6-1-56-63.
    [Ptushkin VV, Minenko SV, Biyachuev ER, et al. Treatment of patients with refractory immune thrombocytopenia: literature review and case report. Onkogematologiya. 2011;1:56–63. doi: 10.17650/1818-8346-2011-6-1-56-63. (In Russ)]
  22. Kuter DJ, Macahiling C, Grotzinger KM, et al. Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia (ITP) switched to eltrombopag or romiplostim. Int J Hematol. 2015,101(3):255–63. doi: 10.1007/s12185-014-1731-7.
  23. Зотова И.И., Абдулкадыров К.М. Опыт применения ромиплостима при хронической иммунной тромбоцитопении, резистентной к предшествующей терапии. Гематология и трансфузиология. 2012;57(3):48–9.
    [Zotova II, Abdulkadyrov KM. Experience in application of romiplostim in chronic immune thrombocytopenia resistant to prior therapy. Gematologiya i transfuziologiya. 2012;57(3):48–9. (In Russ)]
  24. Abdulkadyrov K, Zotova I. The effectiveness and safety of the thrombopoietin (TPO) reсeptor agonists in the treatment of adults with chronic immune thrombocytopenia (ITP) refractory to other treatments. Haematologica. 2013;98(Suppl 1): Abstract B1923.
  25. Zotova I, Abdulkadyrov K. Romiplostim: efficacy and safety in patients with immune thrombocytopenia (ITP). Single center experience. Haematologica. 2014;99(Suppl 1): Abstract P614.
  26. Zotova I, Gritsaev S, Shilova E, et al. Thrombopoietin reсeptor agonists in the treatment of primary ITP: experience of application in clinical practice one medical center. Haematologica. 2016;101(Suppl 1): Abstract PB2091.
  27. Fogarty PF, Tarantino MD, Brainsky A, et al. Selective validation of the WHO Bleeding Scale in patients with chronic immune thrombocytopenia. Curr Med Res Opin. 2012;28(1):79–87. doi: 10.1185/03007995.2011.644849.
  28. Ghanima W, Geyer JT, Lee CS, et al. Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-reсeptor agonists: a single-center, long-term follow-up. Haematologica. 2014;99(5):937–44. doi: 10.3324/haematol.2013.098921.
  29. Brynes RK, Orazi A, Theodore D, et al. Evaluation of bone marrow reticulin in patients with chronic immune thrombocytopenia treated with eltrombopag: data from EXTEND study. Am J Hematol. 2015;90(7):598–601. doi: 10.1002/ajh.24011.