Utilization and Comparative Effectiveness of Caspofungin and Voriconazole Early after Market Approval in the U.S

Objectives Both caspofungin and voriconazole were initially approved by the FDA with very narrow indications. Our aim was to evaluate the utilization patterns and comparative effectiveness of these agents early after marketing before any labeling change occurred. Methods This was a retrospective cohort study utilizing a large healthcare database in the United States. Patients who received at least one dose of systemic antifungal agent between the years 2001 and 2003 were included. Information was available for each hospital-day including underlying conditions, medications, procedures and disease severity scores. Tests for proportions, trend tests and logistic regression were used for evaluation of utilization. Propensity score analysis was used in comparison of mortality. Results The study cohort included 381,245 patients with serious underlying conditions. In just two years after marketing, caspofungin and voriconazole use increased to 40% of the total systemic antifungal consumption. However, only 3.4% of caspofungin and 12.5% of voriconazole were used as indicated in labeling. In the propensity score analyses, caspofungin was associated with 7% decrease in mortality (OR: 0.93 95% CI: 0.85–0.98). Voriconazole use was not found to be associated with mortality (OR: 1 . 95% CI: 0.89–1.12) Conclusions Caspofungin and voriconazole were mostly used of unapproved indications immediately after their marketing. Although unapproved drug use might be due to a crucial need by clinicians, this may create problems in further antifungal drug development. Our results suggest a survival benefit with caspofungin; however, similar comparative effectiveness studies must be repeated using more recent data.