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.
Similar content being viewed by others
References
Marr KA (2001) Antifungal prophylaxis in hematopoietic stem cell transplant recipients. Oncology (Williston Park) 15(11 Suppl 9):15–19
Cornely OA, Ullmann AJ, Karthaus M (2003) Evidence-based assessment of primary antifungal prophylaxis in patients with hematologic malignancies. Blood 101:3365–3372
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
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
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
Uzun O, Anaissie EJ (1995) Antifungal prophylaxis in patients with hematologic malignancies: a reappraisal. Blood 86:2063–2072
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
van Gool R (2001) The cost of treating systemic fungal infections. Drugs 61(Suppl 1):49–56
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
Maertens J, Boogaerts M (2005) The place for itraconazole in treatment. J Antimicrob Chemother 56(Suppl 1):i33–i38
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
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
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
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
Disclosure
We disclose no conflict of interest for this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00520-010-0998-3