The COST-UTILITY ANALYSIS OF FOUR CHELATION REGIMENS FOR ?-THALASSEMIA MAJOR: A CHINESE PERSPECTIVE
Main Article Content
Keywords
cost-utility analysis, β-thalassemia major, deferoxamine, deferiprone, deferasirox
Abstract
Background: The four most commonly used chelation regimens for ?-thalassemia major patients in China are a combination therapy of deferoxamine and deferiprone (DFO+DFP), deferoxamine(DFO) monotherapy, deferiprone(DFP) monotherapy and deferasirox(DFX) monotherapy. Such patients use iron chelators their whole lives, resulting in enormous treatment costs. This study analyses the cost-utility of these four regimens from the Chinese healthcare system perspective.
Methods: A Markov decision model was used over a 70-year time horizon and was populated using clinical data from a systematic literature review. We obtained utility data from local and previous research. Costs were estimated using Chinese national sources.
Results: From the base-case analysis results, DFP was the most cost-effective chelation regimen, followed by DFO+DFP, DFO and DFX. DFP had a 99.60%, 78.10% and 64.40% likelihood of being cost-effective versus DFX, DFO and DFO+DFP, respectively, at a payment threshold of 193,932.00 CNY/QALY.
Conclusions: DFP was the most cost-effective chelation regimen for ?-thalassemia major patients, followed by DFO+DFP, DFO and DFX. Using DFP as the primary treatment regimen may potentially result in cost-savings and QALY gains for the Chinese healthcare system. To increase these benefits, the Chinese government and clinicians should lower drug costs, increase drug utility and reduce mortality and morbidity. Changes in influential parameters easily affect the results of DFO+DFP versus DFP and of DFP versus DFO; clinicians should focus on such parameters and adjust the regimens accordingly.
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References
[2] Ali TT, David JW, Maria DC, Thalassaemia[J].Lancet 2018; 391: 155–67.
[3] Pistoia L, Meloni A, Salvadori S, et al. Cardiac involvement by CMR in different genotypic groups of major thalassemia patients[J]. Blood Cells Mol Dis. 2019 (77):1-7.
[4] Colah R , Gorakshakar A , Nadkarni A . Global burden, distribution and prevention of ?-thalassemias and hemoglobin E disorders[J]. Expert Review of Hematology. 2010,3(1):103-117.
[5] Weatherall, D. J . The inherited diseases of hemoglobin are an emerging global health burden[J]. Blood, 2010, 115(22):4331-4336.
[6] Vincenzo D S . ?-thalassemia distribution in the old world: a historical standpoint of an ancient disease[J]. Mediterranean Journal of Hematology and Infectious Diseases, 2017, 9(1):e2017018.
[7] National Co-ordination Group of Haemoglobinopathy Research. A survey on hemoglobinopathy among 600,000 residents of 20 provinces, cities, and autonomous regions of China[J]. Zhonghua Yi Xue Za Zhi, 1983, 63(6): 382-5.
[8] Yang XQ , Huang QH , Hhuang BL , et al. The analysis on morbidity and genotypes distribution of thalassemia in married couples of child-bearing age in Dongyuan county of Guangdong province[J]. Chinese Journal of Family Planning & Gynecotokology, 2014,6(5),50-56.
[9] Liu P , Huang JG. Analysis of the prenatal screening results of thalassemia in 18704 outpatients in south Jiangxi province[J].China modern doctor, 2018,56(6),16-23.
[10] Zhu WY , Xie DL , Zhang X , et al. Screening results and intervention status of thalassemia in pre-pregnancy couples in Longgang District, Shenzhen[J]. China Tropical Medicine, 2019,9(1),93-96.
[11] Zhou BY , Zhao WZ , Li MZ , et al. Genotyping of 16 336 thalassemia screening positive specimens in Guangdong Province[J]. China Medical Herald, 2016,11(31),73-77.
[12] Ee TA, von Riedemann S, Tricta F. Cost-utility of chelators in transfusion-dependent ?-thalassemia major patients: a review of the pharmacoeconomic literature J. Expert Review of Pharmacoeconomics & Outcomes Research, 2014, 14(5):651-60.
[13] Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the management of transfusion dependent thalassaemia (TDT). 3rd edn. Nicosia, Cyprus: Thalassaemia International Federation, 2014.
[14] Beijing AngelMom Charity Foundation, China Siyuan Foundation for Poverty Alleviation, China Philanthropy Research Institute of Beijing Normal University. Blue Paper of Thalassemia in China [M]. China Social Publishing House.2016.
[15] Subspecialty Groups of Hematology, Society of Pediatrics, Chinese Medical Association; Editorial Board of Chinese Journal of Pediatrics. Guidelines for the diagnosis and treatment of beta-thalassemia major[J]. Chinese journal of pediatrics. 2018, 56(10):724-729.
[16] Label for Desferal® revised:03/2017[EB/OL].
a) http://zy.yaozh.com/instruct/20180606sms/a432.pdf. Accessed 14 September 2019.
[17] Hatzipantelis E S, Karasmanis K, Perifanis V, et al. Combined Chelation Therapy with Deferoxamine and Deferiprone in ?-Thalassemia Major: Compliance and Opinions of Young Thalassemic Patients[J]. Hemoglobin, 2014, 38(2):111-114.
[18] Delea TE , Edelsberg J , Sofrygin O , et al. Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review[J]. Transfusion, 2010, 47(10):1919-1929.
[19] Society of Hematology, Chinese Medical Association?Branch of Hematology Physicians, Chinese Medical Doctor Association. Chinese Expert Consensus on Diagnosis and Treatment of Iron Overload[J]. Chinese Journal of Hematology. 2011, 32(8):572-574.
[20] US Food and Drug Administration. Label for Ferriprox® revised:02/2015[EB/OL]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021825s003lbl.pdf
[21] Label for Exjade® revised:06/2010[EB/OL].
a) http://zy.yaozh.com/instruct/sms201607135/1.jpg. Accessed 14 September 2019.
[22] US Food and Drug Administration. Label for Exjade® revised:05/2019[EB/OL]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021882s031lbl.pdf. Accessed 14 September 2019.
[23] Wijarnpreecha K , Kumfu S , Chattipakorn S C , et al. Cardiomyopathy Associated with Iron Overload: How Does Iron Enter Myocytes and What are the Implications for Pharmacological Therapy[J]. Hemoglobin, 2015, 39(1):9.
[24] Kremastinos D T , Farmakis D , Aessopos A , et al. Beta-Thalassemia Cardiomyopathy: History, Present Considerations, and Future Perspectives[J]. Circulation Heart Failure, 2010, 3(3):451-458.
[25] Carpenter J P , Roughton M , Pennell D J . International survey of T2* cardiovascular magnetic resonance in ?-thalassemia major[J]. Haematologica, 2013, 98(9):1368-1374.
[26] Galanello R , Origa R . Beta-thalassemia[J]. Orphanet Journal of Rare Diseases, 2010, 5(1):11.
[27] Russo V, Rago A, Papa A A, et al. Electrocardiographic Presentation, Cardiac Arrhythmias, and Their Management in ?-Thalassemia Major Patients[J]. Annals of Noninvasive Electrocardiology, 2016, 21(4):335-342.
[28] Pennell D J , Udelson J E , Arai A E , et al. Cardiovascular function and treatment in ?-thalassemia major: a consensus statement from the American Heart Association[J]. Circulation, 2013, 128(13):E203-E203.
[29] Angelucci E , Barosi G , Camaschella C , et al. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders[J]. Haematologica, 2008, 93(5):741-752.
[30] Ho PJ, Tay L, Lindeman R, et al. Australian guidelines for the assessment of iron overload and iron chelation in transfusiondependent thalassaemia major, sickle cell disease and other congenital anaemias[J]. Internal Medicine Journal, 2011, 41(7):516-524.
[31] Paramore C, Vlahiotis A, Moynihan M, et al. Treatment Patterns and Costs of Transfusion and Chelation in Commercially-Insured and Medicaid Patients with Transfusion-Dependent ?-Thalassemia[J]. Blood, 2017,130:5635.
[32] Pepe A , Meloni A , Rossi G , et al. Direct Cost Analysis About The Three Chelators For The Treatment Of Thalassemia Patients With Chronic Iron Overload: An Italian Perspective From The MIOT Network[J]. Blood, 2013, 122(21):5605.
[33] Esmaeilzadeh F, Azarkeivan A, Emamgholipour S, et al. Economic Burden of Thalassemia Major in Iran, 2015[J]. Journal of Research in Health Sciences, 2017, 16(3):111.
[34] Li J., Lin Y., Li X., Zhang J. Economic evaluation of chelation regimens for ?-thalassemia major: a systematic review. Mediterr J Hematol Infect Dis 2019, 11(1): e2019036.
[35] National health commission of the People’s Republic of China. Statistical Bulletin on the Development of Health Career in China in 2017[EB/OL]. http://www.nhc.gov.cn/guihuaxxs/s10743/201806/44e3cdfe11fa4c7f928c879d435b6a18.shtml. Accessed 14 September 2019.
[36] People's Bank of China. Current Renminbi Interest Rate Table (October 24, 2015) [EB/OL]. http://www.pbc.gov.cn/zhengcehuobisi/125207/125213/125440/125838/125885/125896/2968988/index.html. Accessed 14 September 2019.
[37] National Bureau of Statistics of China. The per capita GDP in 2018[EB/OL]. http://data.stats.gov.cn/easyquery.htm?cn=C01&zb=A0201&sj=2018. Accessed 14 September 2019.
[38] WHO. Choosing intervenes that are cost effective(who-choice), threshold values for intervention cost-effectiveness by region [EB/OL]. http:www.who.int/entity/choice/costs/CER_thresholds_regions.xls. Accessed 14 September 2019.
[39] Keshtkaran A , Javanbakht M , Salavati S , et al. Cost–utility analysis of oral deferasirox versus infusional deferoxamine in transfusion?dependent ??thalassemia patients[J]. Transfusion, 2013, 53.
[40] Giardina P J V , Ehlers K H , Engle M A , et al. The Effect of Subcutaneous Deferoxamine on the Cardiac Profile of Thalassemia Major: A Five?Year Study[J]. Annals of the New York Academy of Sciences, 1985, 445(1):282-292.
[41] Wolfe L , Olivieri N , Sallan D , et al. Prevention of Cardiac Disease by Subcutaneous Deferoxamine in Patients with Thalassemia Major[J]. New England Journal of Medicine, 1985, 312(25):1600-1603.
[42] Olivieri N F, McGee A, Liu P, et al. Cardiac disease-free survival in patients with thalassemia major treated with subcutaneous deferoxamine: An update of the Toronto cohort[J]. Annals of the New York Academy of Sciences, 1990, 612: 585-586.
[43] Ehlers K H , Giardina P J , Lesser M L , et al. Prolonged survival in patients with beta-thalassemia major treated with deferoxamine[J]. Journal of Pediatrics, 1991, 118(4-part-P1):540-545.
[44] Richardson M E , Matthews R N , Alison J F , et al. Prevention of heart disease by subcutaneous desferoxamine in patients with thalassaemia major[J]. Internal Medicine Journal, 1993, 23(6):656-661.
[45] Brittenham G M , Griffith P M , Nienhuis A W , et al. Efficacy of Deferoxamine in Preventing Complications of Iron Overload in Patients with Thalassemia Major[J]. New England Journal of Medicine, 1994, 331(9):567-573.
[46] Comparison between deferoxamine and deferiprone (L1) in iron-loaded thalassemia patients.
[47] Li C K , Luk C W , Ling S C , et al. Morbidity and mortality patterns of thalassaemia major patients in Hong Kong: retrospective study.[J]. Hong Kong Med J, 2002, 8(4):255-260.
[48] Piga A , Gaglioti C , Fogliacco E , et al. Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis[J]. Haematologica, 2003, 88(5):489-496.
[49] Aessopos A , Farmakis D , Hatziliami A , et al. Cardiac status in well-treated patients with thalassemia major[J]. European Journal of Haematology, 2004, 73(5):359-366.
[50] Borgnapignatti C , Rugolotto S , De Stefano P , et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine[J]. Haematologica, 2004, 89(10):1187-1193.
[51] Laws H J , G?Bel U , Christaras A , et al. Intensification of Chelating-Therapy in Patients with Thalassemia major[J]. Klinische Padiatrie, 2005, 217(3).
[52] Borgna-Pignatti C , Cappellini M D , Stefano P D , et al. Cardiac morbidity and mortality in Deferoxamine- or Deferiprone-treated patients with thalassemia major[J]. Blood, 2006, 107(9):3733-3737.
[53] Maggio A , Vitrano A , Capra M , et al. Improving survival with deferiprone treatment in patients with thalassemia major: A prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies[J]. Blood Cells Mol Dis, 2009, 42(3):0-251.
[54] Elalfy M S , Abdin I A , El Safy U R , et al. Cardiac events and cardiac T2* in Egyptian children and young adults with ?-thalassemia major taking deferoxamine[J]. Hematology/Oncology and Stem Cell Therapy, 2010, 3(4):174-178.
[55] Lai M E , Grady R W , Vacquer S , et al. Increased survival and reversion of iron-induced cardiac disease in patients with thalassemia major receiving intensive combined chelation therapy as compared to desferoxamine alone[J]. Blood Cells, Molecules, and Diseases, 2010, 45(2):0-139.
[56] Porter J B , Wood J , Nancy Olivieri…. Treatment of heart failure in adults with thalassemia major: response in patients randomised to deferoxamine with or without deferiprone[J]. Journal of Cardiovascular Magnetic Resonance, 2013, 15(1):38.
[57] Pennell D J , Porter J B , Piga A , et al. A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in ?-thalassemia major (CORDELIA)[J]. Blood, 2014, 123(10):1447-1454.
[58] Lin Z Y. Analysis of influencing factors of Treatment compliance and incidence rate complications in children with beta-Thalassemia major[J]. Journal of Qilu Nursing, 2016, 22(6):59-61.
[59] Agarwal M B , Gupte S S , Viswanathan C , et al. Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial[J]. British Journal of Haematology, 1992, 82(2):460-466.
[60] Ayyub M , Ali W , Anwar M , et al. Efficacy and adverse effects of oral iron chelator deferiprone (l1, 1,2- dimethyl-3-hydroxypyrid-4-one) in patients with beta thalassaemia major in Pakistan[J]. Journal of Ayub Medical College Abbottabad Jamc, 2005, 17(4):12-15.
[61] Ladis V , Chouliaras G , Berdoukas V , et al. Relation of chelation regimes to cardiac mortality and morbidity in patients with thalassaemia major: an observational study from a large Greek Unit[J]. European journal of haematology, 2010, 85(4):335-344.
[62] Taher A , Amal El?Beshlawy, Elalfy M S , et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron?overloaded patients with ? ?thalassaemia: the ESCALATOR study[J]. European Journal of Haematology, 2009, 82(6):458-465.
[63] Pennell D J , Porter J B , Cappellini M D , et al. Efficacy of deferasirox in reducing and preventing cardiac iron overload in -thalassemia[J]. Blood, 2010, 115(12):2364-2371.
[64] Gao H Y, Li Q, Chen J J, et al. Curative effects and safety of deferasirox in treatment of iron overload in children with ?-thalassemia major[J]. Chinese Journal of Contemporary Pediatrics, 2011, 13(7):531-534.
[65] Taher A , Elalfy M S , Zir K A , et al. Importance of optimal dosing ?30mg/kg/d during deferasirox treatment: 2.7-yr follow-up from the ESCALATOR study in patients with ?-thalassaemia[J]. European Journal of Haematology, 2011, 87(4):355-365.
[66] Eshghi P. Complications of combined treatment with deferiprone and desferrioxamine in thalassemic patients[J]. Iranian Journal of Medical Sciences, 2007, 32(1): 40-44.
[67] Maggio A , Vitrano A , Capra M , et al. Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial[J]. British Journal of Haematology, 2010, 145(2):245-254.
[68] Kuo H T , Tsai M Y , Peng C T , et al. Pilot Study on the “Quality of Life” as Reflected by Psychosocial Adjustment of Children with Thalassemia Major Undergoing Iron-Chelating Treatment in Western Taiwan[J]. Hemoglobin, 2006, 30(2):291-299.
[69] Drummond M, O'Brien B, Stoddart G, Torrance G. Methods for economic evaluation of healthcare programmes. 4nd ed. Oxford: Oxford Medical Publications; 2015.
[70] Economic evaluation of human papillomavirus vaccine versus Chinese women aged 18 to 25 for treating cervical cancer[J]. Chinese Journal of Evidence-Based Medicine, 2017(1):102-107.
[71] Luangasanatip N , Chaiyakunapruk D N , Upakdee N , et al. Iron-Chelating Therapies in a Transfusion-Dependent Thalassaemia Population in Thailand[J]. Clinical Drug Investigation, 2011, 31(7):493-505.
[72] General Administration of Sport of China. National Physical Fitness Monitoring Bulletin 2014[EB/OL]. http://www.sport.gov.cn/n315/n329/c216784/content.html. Accessed 14 September 2019.
[73] Hong Y . Analysis of Complications of Type 2 Diabetes in Patients with Treatment Costs[J]. Guide of China Medicine, 2015. 13(14):21-22.
[74] Briggs AH. Handling uncertainty in cost-effectiveness models[J]. Pharmacoeconomics. 2000;17(5):479–500.
[75] Briggs AH, Goeree R, Blackhouse G, O’Brien BJ. Probabilistic analysis of cost-effectiveness models: choosing between treatment strategies for gastroesophageal reflux disease[J]. Med Decis Making. 2002;22(4):290–308.
[76] Pepe A, Rossi G, Bentley A, et al. Cost-Utility Analysis of Three Iron Chelators Used in Monotherapy for the Treatment of Chronic Iron Overload in ?-Thalassaemia Major Patients: An Italian Perspective[J]. Clinical Drug Investigation, 2017:1-12.