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Medical cost analysis for antifungal prophylaxis in neutropenic patients with hematological malignancies: a systematic simulation analysis

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Abstract

Goals of work

We assessed the medical costs of different antifungal agents for prophylaxis of invasive fungal infections in neutropenic patients in Japan with a cost simulation model designed for the study.

Patients and methods

We used probabilities of prophylaxis failure, possible cases for empiric therapy, probable proportions of infections caused by fungus species among prophylaxis failure patients, and incidence of adverse events caused by any reason, based on systematic analysis of previously reported randomized trials identified by a computerized search of the PubMed database. Antifungal agents were limited to oral fluconazole, oral itraconazole, micafungin, and liposomal amphotericin B. The range of the expected medical cost was simulated as a sensitivity analysis using 95% of confidence interval of a mean.

Main results

Fifteen studies were identified for our analysis. The prophylactic efficacy was comparable between the four agents. The simulated expected cost for invasive fungal infection prophylaxis and treatment of the infection was $1,035.74 when oral itraconazole was used for prophylaxis, $1,552.81 with oral fluconazole, $2,245.96 with micafungin, and $3,028.10 with liposomal amphotericin B. The total cost including treatment cost for adverse events related to each drug was $2,742.14, $3,547.91, $3,034.57, and $3,028.10, respectively. This result was confirmed in a sensitivity analysis in which IFI incidence and therapy duration were tested as parameters.

Conclusions

Our analysis results suggest that oral itraconazole is the most cost-effective prophylactic antifungal agent for invasive fungal infections in neutropenic patients with hematological malignancies, and this result was robust by sensitivity analysis.

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References

  1. Marr KA (2001) Antifungal prophylaxis in hematopoietic stem cell transplant recipients. Oncology (Williston Park) 15(11 Suppl 9):15–19

    CAS  Google Scholar 

  2. Cornely OA, Ullmann AJ, Karthaus M (2003) Evidence-based assessment of primary antifungal prophylaxis in patients with hematologic malignancies. Blood 101:3365–3372

    Article  PubMed  CAS  Google Scholar 

  3. Walsh TJ, Pappas P, Winston DJ, National Institute of Allergy and Infectious Diseases Mycoses Study Group et al (2002) Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 346:225–234

    Article  PubMed  CAS  Google Scholar 

  4. Walsh TJ, Teppler H, Donowitz GR et al (2004) Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 351:1391–1402

    Article  PubMed  CAS  Google Scholar 

  5. Kuse ER, Chetchotisakd P, da Cunha CA, Micafungin Invasive Candidiasis Working Group (2007) Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369:1519–1527

    Article  PubMed  CAS  Google Scholar 

  6. Uzun O, Anaissie EJ (1995) Antifungal prophylaxis in patients with hematologic malignancies: a reappraisal. Blood 86:2063–2072

    PubMed  CAS  Google Scholar 

  7. Working Group of the invasive fungal infection guideline advisory council (2007) Guidelines of diagnoses and treatment for the invasive fungal infections. Kyowa Kikaku KK, Tokyo

    Google Scholar 

  8. Penack O, Schwartz S, Martus P et al (2006) Low-dose liposomal amphotericin B in the prevention of invasive fungal infections in patients with prolonged neutropenia: results from a randomized, single-center trial. Ann Oncol 17:1306–1312

    Article  PubMed  CAS  Google Scholar 

  9. Kelsey SM, Goldman JM, McCann S, Oppenheim BA, Mufti GJ et al (1999) Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo-controlled study. Bone Marrow Transplant 23:163–168

    Article  PubMed  CAS  Google Scholar 

  10. Ito Y, Ohyashiki K, Yoshida I et al (2007) The prophylactic effect of itraconazole capsules and fluconazole capsules for systemic fungal infections in patients with acute myeloid leukemia and myelodysplastic syndromes: a Japanese multicenter randomized, controlled study. Int J Hematol 85:121–127

    Article  PubMed  CAS  Google Scholar 

  11. Glasmacher A, Cornely O, Ullmann AJ, Itraconazole Research Group of Germany et al (2006) An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia. J Antimicrob Chemother 57:317–325

    Article  PubMed  CAS  Google Scholar 

  12. Huijgens PC, Simoons-Smit AM, van Loenen AC et al (1999) Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology. J Clin Pathol 52:376–380

    Article  PubMed  CAS  Google Scholar 

  13. Cornely OA, Maertens J, Winston DJ et al (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356:348–359

    Article  PubMed  CAS  Google Scholar 

  14. van Burik JA, Ratanatharathorn V, Stepan DE, National Institute of Allergy and Infectious Diseases Mycoses Study Group et al (2004) Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 39:1407–1416

    Article  PubMed  Google Scholar 

  15. Lass-Flörl C, Gunsilius E, Gastl G et al (2003) Fungal colonization in neutropenic patients: a randomized study comparing itraconazole solution and amphotericin B solution. Ann Hematol 82:565–569

    Article  PubMed  Google Scholar 

  16. Mattiuzzi GN, Estey E, Raad I et al (2003) Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome. Cancer 97:450–456

    Article  PubMed  CAS  Google Scholar 

  17. Boogaerts M, Maertens J, van Hoof A et al (2001) Itraconazole versus amphotericin B plus nystatin in the prophylaxis of fungal infections in neutropenic cancer patients. J Antimicrob Chemother 48:97–103

    Article  PubMed  CAS  Google Scholar 

  18. Harousseau JL, Dekker AW, Stamatoullas-Bastard A et al (2000) Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B. Antimicrob Agents Chemother 44:1887–1893

    Article  PubMed  CAS  Google Scholar 

  19. Nucci M, Biasoli I, Akiti T et al (2000) A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients. Clin Infect Dis 30:300–305

    Article  PubMed  CAS  Google Scholar 

  20. Menichetti F, Favero AD, Martino P et al (1999) Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. Clin Infect Dis 28:250–255

    Article  PubMed  CAS  Google Scholar 

  21. Rotstein C, Bow EJ, Laverdiere M et al (1999) Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian fluconazole prophylaxis study group. Clin Infect Dis 28:331–340

    Article  PubMed  CAS  Google Scholar 

  22. Morgenstern GR, Prentice AG, Prentice HG et al (1999) A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Br J Haematol 105:901–911

    Article  PubMed  CAS  Google Scholar 

  23. Robenshtok E, Gafter-Gvili A, Goldberg E et al (2007) Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis. J Clin Oncol 25:5471–5489

    Article  PubMed  CAS  Google Scholar 

  24. de Vries R, Daenen S, Tolley K et al (2008) Cost effectiveness of itraconazole in the prophylaxis of invasive fungal infections. Pharmacoeconomics 26:75–90

    Article  PubMed  Google Scholar 

  25. van Gool R (2001) The cost of treating systemic fungal infections. Drugs 61(Suppl 1):49–56

    Article  PubMed  Google Scholar 

  26. Pignone M, Saha S, Hoerger T et al (2005) Challenges in systematic reviews of economic analyses. Ann Intern Med 142(12 Pt 2):1073–1079

    PubMed  Google Scholar 

  27. Maertens J, Boogaerts M (2005) The place for itraconazole in treatment. J Antimicrob Chemother 56(Suppl 1):i33–i38

    Article  PubMed  CAS  Google Scholar 

  28. CDC, Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation (2001) Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. Cytotherapy 3:41–54

    Google Scholar 

  29. Imataki O, Kami M, Kim SW (2004) A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan. Bone Marrow Transplant 33:1173–1179

    Article  PubMed  CAS  Google Scholar 

  30. Goodman JL, Winston DJ, Greenfield RA et al (1992) A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 326:845–851

    Article  PubMed  CAS  Google Scholar 

  31. Slavin MA, Osborne B, Adams R et al (1995) Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation—a prospective, randomized, double-blind study. J Infect Dis 171:1545–1552

    Article  PubMed  CAS  Google Scholar 

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Disclosure

We disclose no conflict of interest for this study.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Osamu Imataki & Hiroaki Ohnishi

  2. Department of Transfusion Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Yoshitsugu Kubota

  3. Department of Laboratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Akira Kitanaka

  4. Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Toshihiko Ishida

  5. Environmental Health Sciences, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Terukazu Tanaka

Authors
  1. Osamu Imataki
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  2. Yoshitsugu Kubota
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  3. Hiroaki Ohnishi
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  4. Akira Kitanaka
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  5. Toshihiko Ishida
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  6. Terukazu Tanaka
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Correspondence to Osamu Imataki.

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Imataki, O., Kubota, Y., Ohnishi, H. et al. Medical cost analysis for antifungal prophylaxis in neutropenic patients with hematological malignancies: a systematic simulation analysis. Support Care Cancer 19, 1657–1665 (2011). https://doi.org/10.1007/s00520-010-0998-3

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  • DOI: https://doi.org/10.1007/s00520-010-0998-3

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