International Journal of Hematology

, Volume 107, Issue 2, pp 235–243 | Cite as

Fluconazole versus mould-active triazoles for primary antifungal prophylaxis in adult patients with acute lymphoblastic leukemia: clinical outcome and cost-effectiveness analysis

Original Article

Abstract

This study evaluated the clinical and cost-effectiveness of prophylactic use of fluconazole versus mould-active triazoles (voriconazole and posaconazole) in adult patients with acute lymphoblastic leukemia (ALL). A decision analytical model was developed with inputs from a 7-year retrospective study (2009–2016) of 103 consecutive adult patients with ALL who received antifungal prophylaxis. Information on the administration of antifungal agents, clinical outcomes, and costs were collected. One-way sensitivity analyses and probabilistic sensitivity analysis were performed. The mould-active triazoles group was associated with higher life-years (3.71 vs 3.59) and lower total costs (US$4886 vs US$5722) per patient compared with fluconazole. One-way sensitivity analyses revealed that varying all of the key variables in the model did not affect the robustness of the results. Probabilistic sensitivity analysis demonstrated that mould-active triazoles had a probability of 77.1 and 90.1% of providing a dominant and cost-effective option relative to fluconazole, respectively. Mould-active triazoles should be regarded as preferable to fluconazole as the first-line prophylactic for adult patients with ALL accompanied by uncommon severe vinca alkaloid-induced neurotoxicity. However, the results reported here should be interpreted with caution owing to the observational nature of the data.

Keywords

Cost-effectiveness Antifungal agents Prophylaxis Acute lymphoblastic leukemia 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81473177 and 81672954) and the Natural Science Foundation of Shaanxi Province (No. 2016JM8015).

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.

References

  1. 1.
    Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006;91:986–9.PubMedGoogle Scholar
  2. 2.
    Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.PubMedGoogle Scholar
  3. 3.
    NCT01259713. Prevention of invasive fungal infections (IFIs) in subjects receiving chemotherapy for acute lymphoblastic leukemia. 2010. http://clinicaltrials.gov/ct2/show/study/NCT01259713.
  4. 4.
    Pagano L, Busca A, Candoni A, Cattaneo C, Cesaro S, Fanci R, et al. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations. Blood Rev. 2017;31:17–29.CrossRefPubMedGoogle Scholar
  5. 5.
    Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32:358–66.CrossRefPubMedGoogle Scholar
  6. 6.
    Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15.CrossRefPubMedGoogle Scholar
  7. 7.
    Ananda-Rajah MR, Cheng A, Morrissey CO, Spelman T, Dooley M, Neville AM, et al. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach. Antimicrob Agents Chemother. 2011;55:1953–60.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    NCCN Guidelines Version 2.2016 of Acute Lymphoblastic Leukemia [Internet]. American: National Comprehensive Cancer Network. http://www.nccn.org/. Accessed 20 Sept 2016.
  9. 9.
    Pfaller MA, Diekema DJ, Sheehan DJ. Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Clin Microbiol Rev. 2006;19:435–47.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Astellas Pharma Europe B.V. Mycamine: summary of product characteristics. https://www.medicines.org.uk/emc/medicine/20997/SPC/Mycamine+50mg+and+100mg+powder+for+solution+for+infusion/. Accessed 20 Sept 2016.
  11. 11.
    Doan TN, Kirkpatrick CMJ, Walker P, Slavin MA, Ananda-Rajah MR, Morrissey CO, et al. Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit. J Antimicrob Chemother. 2016;71:497–505.CrossRefPubMedGoogle Scholar
  12. 12.
    Sun Y, Huang H, Chen J, Li J, Ma J, Li J, et al. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China. Tumour Biol. 2015;36:757–67.CrossRefPubMedGoogle Scholar
  13. 13.
    Pfizer Inc. Vfend (voriconazole) package insert. New York; 2008.Google Scholar
  14. 14.
    Merck Inc. Noxafil (posaconazole) package insert. Darmstadt; 2012.Google Scholar
  15. 15.
    Bohme A, Just-Nubling G, Bergmann L, Shah PM, Stille W, Hoelzer D. Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies. J Antimicrob Chemother. 1996;38:953–61.CrossRefPubMedGoogle Scholar
  16. 16.
    Niwa T, Imagawa Y, Yamazaki H. Drug interactions between nine antifungal agents and drugs metabolized by human cytochromes P450. Curr Drug Metab. 2014;15:651–79.CrossRefPubMedGoogle Scholar
  17. 17.
    Al-Badriyeh D, Slavin M, Liew D, Thursky K, Downey M, Grigg A, et al. Pharmacoeconomic evaluation of voriconazole versus posaconazole for antifungal prophylaxis in acute myeloid leukaemia. J Antimicrob Chemother. 2010;65:1052–61.CrossRefPubMedGoogle Scholar
  18. 18.
    Grau S, de la Camara R, Sabater FJ, Jarque I, Carreras E, Casado MA, et al. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain. BMC Infect Dis. 2012;12:83.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Heng SC, Slavin MA, Al-Badriyeh D, Kirsa S, Seymour JF, Grigg A, et al. Pharmacoeconomic evaluation of fluconazole, posaconazole and voriconazole for antifungal prophylaxis in patients with acute myeloid leukaemia undergoing first consolidation chemotherapy. J Antimicrob Chemother. 2013;68:1669–78.CrossRefPubMedGoogle Scholar
  20. 20.
    Mauskopf J, Chirila C, Graham J, Gersten ID, Leather H, Maziarz RT, et al. Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants. Am J Health Syst Pharm. 2013;70:1518–27.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zhao YJ, Khoo AL, Tan G, Teng M, Tee C, Tan BH, et al. Network meta-analysis and pharmacoeconomic evaluation of fluconazole, itraconazole, posaconazole, and voriconazole in invasive fungal infection prophylaxis. Antimicrob Agents Chemother. 2016;60:376–86.CrossRefGoogle Scholar
  22. 22.
    De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    National Health and Family Planning Commission of the People’s Republic of China. Chinese Statistical Yearbook of Health and Family Planning of 2015. Beijing: Peking Union Medical University; 2015.Google Scholar
  24. 24.
    WHO-CHOICE. Geneva: World Health Organization. http://www.who.int/choice/costs/CER_thresholds/en/ Accessed 20 Sept 2016.
  25. 25.
    Lewis G, Hall P, Eisa N, Deremer D, Dobbins R, El-Geneidy M, et al. Acute myelogenous leukemia patients are at low risk for invasive fungal infections after high-dose cytarabine consolidations and thus do not require prophylaxis. Acta Haematol. 2010;124:206–13.CrossRefPubMedGoogle Scholar
  26. 26.
    Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356:348–59.CrossRefPubMedGoogle Scholar
  27. 27.
    Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007;356:335–47.CrossRefPubMedGoogle Scholar
  28. 28.
    Wingard JR, Carter SL, Walsh TJ, Kurtzberg J, Small TN, Baden LR, et al. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010;116:5111–8.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Sculpher MJ, Claxton K, Drummond M, McCabe C. Whither trial-based economic evaluation for health care decision making? Health Econ. 2006;15:677–87.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Yan Wang
    • 1
  • Yuanming Xing
    • 2
  • Lu Chen
    • 1
  • Ti Meng
    • 1
  • Ying Li
    • 1
  • Jiao Xie
    • 1
  • Limei Chen
    • 3
  • Yalin Dong
    • 1
  • Weihua Dong
    • 1
  1. 1.Department of PharmacyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  2. 2.Hou Zonglian Medical Class of 2014Xi’an Jiaotong UniversityXi’anChina
  3. 3.Department of HematologyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

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