The high incidence of adverse reactions associated with treatment with conventional amphotericin B and the incremental cost associated with lipid formulations of this active ingredient make it necessary to consider other therapeutic alternatives that have superior clinical and economic profiles. The pharmacoeconomic model proposed in this study compared two drugs recently introduced on the Spanish market that have been shown to be effective in the treatment of severe aspergillosis. For this purpose, the mean expected cost per episode treated for an average patient with invasive aspergillosis was calculated from the data obtained in a local study that collected data on the duration and patterns of management of these infections in Spanish tertiary hospitals (Fungcost study).
The cost of treatment of invasive aspergillosis was lower with voriconazole than with caspofungin because of the different acquisition costs of these drugs and their particular posology. The large difference in cost between the two drugs decreased as patient bodyweight approached 79kg (the point at which the dose of caspofungin should be increased). From this point until a bodyweight of 103.42kg, where the cost of treatment with the two drugs was equal (threshold value), the cost of treatment continued to be lower with voriconazole. For weights above this threshold value, caspofungin had a lower cost than voriconazole for the treatment of invasive aspergillosis. However, such bodyweights are highly infrequent in the Spanish population; only 1.75% of 21 120 individuals interviewed in the 2001 National Health Survey had bodyweights >101kg, with a mean weight of 70.52kg (SD 13.14kg). Given the mean bodyweight observed in the Fungcost study (68.6kg), the differences in costs in the use of the two treatments can represent a substantial part of the hospital budgets devoted to the treatment of invasive aspergillosis.
Most fungal infections occur in patients hospitalised for other diseases and often affect severely ill patients hospitalised in intensive care units, thus increasing the length of hospitalisation of these patients. The component that contributes most to the total cost of a fungal infection is the length of stay in the hospital, which depends mainly on the duration of IV therapy.
No data are available on the duration of IV therapy with caspofungin and voriconazole in the Spanish setting. However, a review of the clinical experience published worldwide shows that the duration of IV therapy with these agents appears to be similar to that observed for other antifungal agents in the Fungcost study. The two dosage forms of voriconazole (parenteral and oral) allow sequential therapy with the same active ingredient, as well as a reduction in the number of days of IV therapy at the expense of oral continuation therapy. In addition to the lower pharmacological cost of voriconazole compared with caspofungin, this means that a reduction in the cost per patient treated is plausible.
Limitations of the Model
Because of the limited clinical experience available, estimation of efficacy could not be based on the results of a comparative clinical trial with both compounds.
The published data on the efficacy of voriconazole in invasive aspergillosis derive from a randomised, unblinded, comparative study versus amphotericin B by Herbrecht et al., which supports the efficacy of voriconazole as initial therapy in immunocompromised patients, who had a complete or partial response, and an open, noncomparative study by Denning et al., which evaluated the efficacy of voriconazole in immunocompromised patients with histopathological evidence of tissue invasion or a positive culture for Aspergillus spp. from a sterile site, as well as radiological evidence of acute invasive aspergillosis. These patients could receive voriconazole either as first-line or as second-line therapy if they had previously received amphotericin B or itraconazole and initial therapy failed or they were intolerant of the treatment. In this study, efficacy was measured by the sum of all patients who had a complete response (defined as resolution of all clinical signs and symptoms attributable to invasive aspergillosis and complete or nearly complete radiological resolution) or a partial response (improvement or resolution of all clinical signs and symptoms attributable to invasive aspergillosis and ≥50% improvement in radiological findings).
The efficacy of caspofungin in patients with a definitive or probable diagnosis of invasive aspergillosis was established in an open, noncomparative study of patients refractory to or intolerant of antifungal medication, in which a favourable response included patients who had a complete response (resolution of all clinical signs and symptoms attributable to invasive aspergillosis and complete resolution of all radiological or bronchoscopic abnormalities) or a partial response (significant clinical improvement in all clinical signs and symptoms attributable to invasive aspergillosis and a significant ≥50% improvement in radiological and bronchoscopic abnormalities).
Both the design of the trials and the number, heterogeneity, diagnosis and clinical characteristics of the patients are important limitations that lead to tentative presumptions that the two compounds are not similar in their potential efficacy. This presumption is clearly reflected in the indications for the two antifungal agents (first-line for voriconazole and second-line for caspofungin). Even so, it is clear that both antifungal agents are highly effective in the treatment of invasive aspergillosis. Any differences between the two agents could be confirmed in subsequent cost-effectiveness economic analyses that can be conducted after head-to-head clinical trials or clinical experience published in homogenous populations with both drugs become available.
With regard to adverse effects, it should be mentioned that voriconazole frequently causes other adverse effects, such as visual disturbances and skin reactions, which were not included in this analysis because they are moderate, do not cause discontinuation of treatment and do not result in an increase in costs.
Another limitation that should be considered in the determination of costs is that this study did not consider the effect of adverse reactions on prolongation of hospital stay as a result of their treatment, dose reduction, treatment discontinuation or the death of the patient.
Clin Drug Invest. 2007;27(3):197-205. © 2007 Adis Data Information BV
Cite this: Economic Evaluation of Voriconazole versus Caspofungin for the Treatment of Invasive Aspergillosis in Spain - Medscape - Mar 01, 2007.