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Published in: PharmacoEconomics 1/2008

01-01-2008 | Original Research Article

Cost Effectiveness of Itraconazole in the Prophylaxis of Invasive Fungal Infections

Authors: Dr Robin de Vries, Simon Daenen, Keith Tolley, Axel Glasmacher, Archie Prentice, Sarah Howells, Hariette Christopherson, Lolkje T. W. de Jong-van den Berg, Maarten J. Postma

Published in: PharmacoEconomics | Issue 1/2008

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Abstract

Background

Invasive fungal infections in neutropenic patients treated for haematological malignancies are associated with a high mortality rate and, therefore, require early treatment. As the diagnosis of invasive fungal infections is difficult, effective antifungal prophylaxis is desirable. So far, fluconazole has been the most commonly used.

Objective

To assess the cost effectiveness of itraconazole compared with both fluconazole and no prophylaxis for the prevention of invasive fungal infections in haematological patients, mean age 51 years, in Germany and The Netherlands.

Study design

We designed a probabilistic decision model to fully incorporate the uncertainty associated with the risk estimates of acquiring an invasive fungal infection. These risk estimates were extracted from two meta-analyses, evaluating the effectiveness of fluconazole and itraconazole and no prophylaxis. The perspective of the analysis was that of the healthcare sector; only medical costs were taken into account. All costs were reported in €, year 2004 values.
Cost effectiveness was expressed as net costs per invasive fungal infection averted. No discounting was performed, as the model followed patients during their neutropenic period, which was assumed to be less than 1 year.

Results

According to our probabilistic decision model, the monetary benefits of averted healthcare exceed the costs of itraconazole prophylaxis under baseline assumptions (95% CI: from cost-saving to €5000 per invasive fungal infection averted). Compared with fluconazole, itraconazole is estimated to be both more effective and more economically favourable, with a probability of almost 98%.

Conclusions

In specific groups of neutropenic patients treated for haematological malignancies, itraconazole prophylaxis could potentially reduce overall healthcare expenditure, without harming effectiveness, in settings where fluconazole is common practice in the prophylaxis of invasive fungal infections.
Footnotes
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
Literature
1.
go back to reference McNeil MM, Nash SL, Hajjeh RA, et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 2001; 33: 641–647PubMedCrossRef McNeil MM, Nash SL, Hajjeh RA, et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 2001; 33: 641–647PubMedCrossRef
3.
go back to reference Prentice HG, Kibbler CC, Prentice AG. Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol 2000; 100: 273–284CrossRef Prentice HG, Kibbler CC, Prentice AG. Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol 2000; 100: 273–284CrossRef
4.
go back to reference Uzun O, Anaisse EJ. Antifungal prophylaxis in patients with hematologic malignancies: a reappraisal. Blood 1995; 86: 2063–2072PubMed Uzun O, Anaisse EJ. Antifungal prophylaxis in patients with hematologic malignancies: a reappraisal. Blood 1995; 86: 2063–2072PubMed
5.
go back to reference Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001; 32: 358–366PubMedCrossRef Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001; 32: 358–366PubMedCrossRef
6.
go back to reference Rinaldi MG. Problems in the diagnosis of invasive fungal diseases. Rev Infect Dis 1991; 13: 493–495PubMedCrossRef Rinaldi MG. Problems in the diagnosis of invasive fungal diseases. Rev Infect Dis 1991; 13: 493–495PubMedCrossRef
7.
go back to reference Kanda Y, Yamamoto R, Chizuka A, et al. Prophylactic action of oral fluconazole against fungal infection of neutropenic patients: a meta-analysis of 16 randomized, controlled trials. Cancer 2000; 89: 1611–1625PubMedCrossRef Kanda Y, Yamamoto R, Chizuka A, et al. Prophylactic action of oral fluconazole against fungal infection of neutropenic patients: a meta-analysis of 16 randomized, controlled trials. Cancer 2000; 89: 1611–1625PubMedCrossRef
8.
go back to reference Glasmacher A, Prentice A, Gorschliiter M, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a metaanalysis of3,597 patients. J Clin Oncol 2003; 21 (24): 4615–4626PubMedCrossRef Glasmacher A, Prentice A, Gorschliiter M, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a metaanalysis of3,597 patients. J Clin Oncol 2003; 21 (24): 4615–4626PubMedCrossRef
9.
go back to reference Sutton AJ, Abrams KR, Jones DR, et al. Methods for meta-analysis in medical research. Chichester: John Wiley & Sons Ltd, 2000 Sutton AJ, Abrams KR, Jones DR, et al. Methods for meta-analysis in medical research. Chichester: John Wiley & Sons Ltd, 2000
10.
11.
go back to reference Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992; 326: 845–851PubMedCrossRef Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992; 326: 845–851PubMedCrossRef
12.
go back to reference Winston DJ, Chandrasekar PH, Lazarus HM, et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia: results of a randomized placebo-controlled, double blind, multi-center trial. Ann Intern Med 1993; 118: 495–503PubMed Winston DJ, Chandrasekar PH, Lazarus HM, et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia: results of a randomized placebo-controlled, double blind, multi-center trial. Ann Intern Med 1993; 118: 495–503PubMed
13.
go back to reference Chandrasekar PH, Gatny CM. Effect of fluconazole prophylaxis on fever and use of amphotericin in neutropenic cancer patients: the Bone Marrow Transplantation Team. Chemotherapy 1994; 40: 136–143PubMedCrossRef Chandrasekar PH, Gatny CM. Effect of fluconazole prophylaxis on fever and use of amphotericin in neutropenic cancer patients: the Bone Marrow Transplantation Team. Chemotherapy 1994; 40: 136–143PubMedCrossRef
14.
go back to reference Chandrasekar PH, Gathy CM. The effect of fluconazole prophylaxis on fungal colonization in neutropenic cancer patients: the Bone Marrow Transplantation Team. J Antimicrob Chemother 1994; 33: 309–318PubMedCrossRef Chandrasekar PH, Gathy CM. The effect of fluconazole prophylaxis on fungal colonization in neutropenic cancer patients: the Bone Marrow Transplantation Team. J Antimicrob Chemother 1994; 33: 309–318PubMedCrossRef
15.
go back to reference Schafftier A, Schaffner M. Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis 1995; 172: 1035–1041CrossRef Schafftier A, Schaffner M. Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis 1995; 172: 1035–1041CrossRef
16.
go back to reference Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after bone marrow transplantation: a prospective, randomised, double-blind study. J Infect Dis 1995; 171: 1545–1552PubMedCrossRef Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after bone marrow transplantation: a prospective, randomised, double-blind study. J Infect Dis 1995; 171: 1545–1552PubMedCrossRef
17.
go back to reference Kern W, Behre G, Rudolf T, et al. Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia. Cancer 1998; 83: 289–301CrossRef Kern W, Behre G, Rudolf T, et al. Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia. Cancer 1998; 83: 289–301CrossRef
18.
go back to reference Rotstein C, Bow EJ, Laverdiere M, et al. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. Clin Infect Dis 1999; 28: 331–340PubMedCrossRef Rotstein C, Bow EJ, Laverdiere M, et al. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. Clin Infect Dis 1999; 28: 331–340PubMedCrossRef
19.
go back to reference Altaian DG. Practical statistics for medical research. Boca Raton (FL): CRC Press, 1999 Altaian DG. Practical statistics for medical research. Boca Raton (FL): CRC Press, 1999
20.
go back to reference Winston DJ, Maziarz RT, Chandrasekar PH, et al. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients: a multicenter, randomized trial. Ann Intern Med 2003; 138: 705–713PubMed Winston DJ, Maziarz RT, Chandrasekar PH, et al. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients: a multicenter, randomized trial. Ann Intern Med 2003; 138: 705–713PubMed
21.
go back to reference Marr KA, Crippa F, Leisenring W. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Transplantation 2004; 103 (4): 1527–1533 Marr KA, Crippa F, Leisenring W. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Transplantation 2004; 103 (4): 1527–1533
22.
go back to reference Glasmacher A, Cornely O, Ullman AJ. An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patents with haematological malignancy and profound neutropenia. J Antimicrob Chemother 2006; 57: 317–325PubMedCrossRef Glasmacher A, Cornely O, Ullman AJ. An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patents with haematological malignancy and profound neutropenia. J Antimicrob Chemother 2006; 57: 317–325PubMedCrossRef
23.
go back to reference Prismant: National LMR information [online and further data specifically requested]. Available from URL: http://cognosserver.prismant.nl/cognos7/cgi-bin/ppdscgi.cgi?DC=Q&E=/Prisma-Landelijke-LMR/Landelij ke+LMR-informatie+-+Diagnosen [Accessed 2006 Jul 01] Prismant: National LMR information [online and further data specifically requested]. Available from URL: http://​cognosserver.​prismant.​nl/​cognos7/​cgi-bin/​ppdscgi.​cgi?​DC=​Q&​E=​/​Prisma-Landelijke-LMR/​Landelij ke+LMR-informatie+-+Diagnosen [Accessed 2006 Jul 01]
24.
go back to reference Health Care Insurance Board. Dutch pharmacoeconomic guidelines 2004 [in Dutch]. Amstelveen: Health Care Insurance Board, 2003 [online]. Available from URL: http://www.fk.cvz.nl [Accessed 2006 Jul 01] Health Care Insurance Board. Dutch pharmacoeconomic guidelines 2004 [in Dutch]. Amstelveen: Health Care Insurance Board, 2003 [online]. Available from URL: http://​www.​fk.​cvz.​nl [Accessed 2006 Jul 01]
25.
go back to reference Oosterink JB, Bouwmans CAM, Koopmanschap MA, et al. Guideline for costing research, methods and standardized prices for economic evaluations in health care. Diemen: Health Care Insurance Board, 2004 Oosterink JB, Bouwmans CAM, Koopmanschap MA, et al. Guideline for costing research, methods and standardized prices for economic evaluations in health care. Diemen: Health Care Insurance Board, 2004
26.
go back to reference Neilson AR, Moerer O, Burchardi H, et al. A new concept for DRG-based reimbursement of services in German intensive care units: results of a pilot study. Intensive Care Med 2004; 30 (6): 1220–1223PubMedCrossRef Neilson AR, Moerer O, Burchardi H, et al. A new concept for DRG-based reimbursement of services in German intensive care units: results of a pilot study. Intensive Care Med 2004; 30 (6): 1220–1223PubMedCrossRef
30.
go back to reference Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 2000; 17 (5): 479–500PubMedCrossRef Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 2000; 17 (5): 479–500PubMedCrossRef
31.
go back to reference Black WC. The CE plane: a graphic representation of cost-effectiveness. Med Decis Making 1990; 10 (3): 212–214PubMedCrossRef Black WC. The CE plane: a graphic representation of cost-effectiveness. Med Decis Making 1990; 10 (3): 212–214PubMedCrossRef
32.
go back to reference Bos JM, Postma MJ. Using pharmacoeconomics for policy making: is rational decision making enhanced by applying thresholds for cost-effectiveness? Expert Rev Pharmacoeconomics Outcomes Res 2004; 4 (3): 247–250CrossRef Bos JM, Postma MJ. Using pharmacoeconomics for policy making: is rational decision making enhanced by applying thresholds for cost-effectiveness? Expert Rev Pharmacoeconomics Outcomes Res 2004; 4 (3): 247–250CrossRef
33.
go back to reference Wilson LS, Reyes CM, Stolpman M, et al. The direct cost and incidence of systematic fungal infections. Value Health 2002; 5 (1): 26–34PubMedCrossRef Wilson LS, Reyes CM, Stolpman M, et al. The direct cost and incidence of systematic fungal infections. Value Health 2002; 5 (1): 26–34PubMedCrossRef
34.
go back to reference Torfs K. Economic aspects of treatment for fungal infections in cancer patients. Eur J Microbiol Infect Dis 1997; 16: 98–107CrossRef Torfs K. Economic aspects of treatment for fungal infections in cancer patients. Eur J Microbiol Infect Dis 1997; 16: 98–107CrossRef
35.
go back to reference Menzin J, Lang KM, Friedman M, et al. Excess mortality, length of stay, and costs associated with serious fungal infections among elderly cancer patients: findings from linked SEER-Medicare data. Value Health 2005; 8 (2): 140–148PubMedCrossRef Menzin J, Lang KM, Friedman M, et al. Excess mortality, length of stay, and costs associated with serious fungal infections among elderly cancer patients: findings from linked SEER-Medicare data. Value Health 2005; 8 (2): 140–148PubMedCrossRef
36.
go back to reference Gotzsche PC, Johansen HK. Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia. BMJ 1997; 314: 1238–1244PubMedCrossRef Gotzsche PC, Johansen HK. Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia. BMJ 1997; 314: 1238–1244PubMedCrossRef
37.
go back to reference Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998; 27: 781–788PubMedCrossRef Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998; 27: 781–788PubMedCrossRef
38.
go back to reference Jansen JP, Meis JF, Blijlevens NM, et al. Economic evaluation of voriconazole in the treatment of invasive fungal infections in the Netherlands. Curr Med Res Opin 2005; 12 (10): 1535–1546CrossRef Jansen JP, Meis JF, Blijlevens NM, et al. Economic evaluation of voriconazole in the treatment of invasive fungal infections in the Netherlands. Curr Med Res Opin 2005; 12 (10): 1535–1546CrossRef
Metadata
Title
Cost Effectiveness of Itraconazole in the Prophylaxis of Invasive Fungal Infections
Authors
Dr Robin de Vries
Simon Daenen
Keith Tolley
Axel Glasmacher
Archie Prentice
Sarah Howells
Hariette Christopherson
Lolkje T. W. de Jong-van den Berg
Maarten J. Postma
Publication date
01-01-2008
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 1/2008
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.2165/00019053-200826010-00007

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