costs (per patient) in patients who received micafungin (US$121,098) than in those who received fluconazole (US$124,957). The lower incidence of proven or probable IFDs in micafungin arm (1.6%) versus fluconazole arm (2.4%) were associated with total cost savings of US$3859.11
Echinocandins in the empirical and pre-emptive antifungal therapy Empirical therapy is an early approach in patients with persistently febrile neutropenia unresponsive to antibiotic therapy. Pre-emptive therapy is usually based on the presence of specific clinical signs and fungal biomarkers, but there is no consensus on the definition and there may be overlap with empirical and targeted therapy. For empirical therapy, liposomal amphotericin B and caspofungin are recommended as the first-line drugs followed by micafungin and voriconazole. The main drivers of cost in empirical antifungal therapy are drug-acquisition costs plus associated hospitalisation. In a pre-emptive strategy, higher cost of diagnostic procedures should be also taken into account.
A number of pharmacoeconomic analyses that compared liposomal amphotericin B with caspofungin were performed. All of these analyses documented that caspofungin is at least as cost-effective as liposomal amphotericin B. The US-based study evaluated both drug-acquisition costs and costs associated with nephrotoxicity in empirical therapy of neutropenic fever. The overall treatment cost per patient for caspofungin (acquisition cost + cost of nephrotoxicity) was over US$5000 less than for liposomal amphotericin B.12
Two papers that evaluated the cost-effectiveness of empiric therapy comparing caspofungin and voriconazole were published recently. The first was performed in Turkey and the second in Australia. The aim of the Turkish study was to investigate the cost-effectiveness of caspofungin versus voriconazole using a decision analytic model built on two RCTs and input from an expert panel of clinicians. The results of this study documented a prefrence towards caspofungin and will aid in formulary decision-making in their centres.13
Australian study used a similar approach in terms of analysing the health economic impact of using voriconazole versus caspofungin in patients with febrile
neutropaenia. Caspofungin appears to be a more cost-saving drug than voriconazole for empirical therapy, however, the difference was not statistically significant.14
Limited information is
available comparing cost-effectiveness of pre-emptive versus empirical strategies for IFD. Overall, empirical or potentially empirical antifungal use ranged from 35–61.3%, while pre-emptive antifungal use ranged from 7.7–39.4%. Thus, the majority of studies comparing both approaches demonstrated an overall decrease in antifungal use by 43–78% with the use of a pre-emptive treatment versus empirical strategy. A benefit in terms of cost and LOS in high-risk patients has been suggested for pre-emptive treatment.15
Prophylaxis and treatment of invasive aspergillosis IA is the most common IFD in haematological patients especially in centres with leukaemia and transplanted patients. The additional IA cost burden ranged from €10,530–€25,550, and was statistically significantly greater in patients with IA versus patients without IA.16
drugs of choice for the treatment of IA are voriconazole and liposomal amphotericin B; echinocandins (caspofungin and micafungin) are used as a salvage therapy. The economic evaluation of echinocandins in this indication as well as in the setting of combination therapy (echinocandin + voriconazole or polyene) is not reported.
Based on the current knowledge, and despite the limitations of pharmacoeconomic studies, use of echinocandins in the treatment of IFD (especially in IC) is associated with cost-savings or cost-effectiveness. Despite their higher aquisition cost the economic benefit is maitained due to high clinical efficacy and lower incidence of adverse events and shorter length of
hospitalisation, which affect the direct and indirect costs. Well-designed clinical trials should incorporate the economic parameters as an endpoint to facilitate the decisions from hospital, payers and societal perspective. ●
References 1. Drgona L et al. Clinical and economic burden of invasive fungal diseases in Europe: focus on pre-emptive and empirical treatment of Aspergillus and Candida species. Eur J Clin Microbiol Infect Dis 2014;33:7–21.
2. Wilson LS et al. The direct cost and incidence of systemic fungal infections. Value Health 2002;5:26–34.
3. Neoh CF et al. Echinocandins in the treatment of candidaemia and invasive candidiasis: clinical and economic perspectives. Int J Antimicrob Agents 2014 43;207–14.
4. Cornely OA et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012;18(Suppl. 7):19–37.
5. Gafter-Gvili A et al. Treatment of invasive candidal infections: systematic review and meta-analysis. Mayo Clin Proc 2008;83:1011–21.
6. Andes DR et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis 2012;54:1110–22.
7. Reboli AC et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007;356(24):2472–82.
8. Garcia M et al. Budget impact analysis of three candins in the treatment of invasive candidiasis in adult non-neutropenic patients in Spain. In: Abstracts of the 12th Annual European congress of the ISPOR 2009, abstract PIN12.
9. Grau S et al. Cost effectiveness analysis of 3 candins and fluconazole in the treatment of confirmed invasive candidiasis in adult non-neutropenic patients in Spain. Value in Health, 2013;16:A351–A352.
10. Masterton R et al. Cost effectiveness of de- escalation from micafungin in the treatment of patients with systemic Candida infections compared to traditional escalation from fluconazole. Value in Health 2011;14:A279–A279.
11. Schonfeld W et al. Cost-effectiveness analysis of antifungal prophylaxis in patients undergoing hematopoietic stem cell transplantation. Clin Ther 2008;30:964–73.
12. Wingard JR et al. Pharmacoeconomic analysis of caspofungin versus liposomal amphotericin B as empiric therapy for neutropenic fever. Am J Health-Syst Pharm 2007;64:637–3.
13. Turner SJ et al. Cost effectiveness of caspofungin vs. voriconazole for empiric therapy in Turkey. Mycoses 2014;57:489–96.
14. Al-Badriyeh D et al. Pharmacoeconomic analysis of voriconazole vs. caspofungin in the empirical antifungal therapy of febrile neutropenia in Australia. Mycoses 2012;55:244–56.
15. Barnes RA et al. Clinical impact of enhanced diagnosis of invasive fungal disease in high-risk haematology and stem cell transplant patients. J Clin Pathol 2009;62:64–9.
16. Slobbe L et al. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: an observational study. Clin Infect Dis 2008;47: 1507–12.
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