Cost-Effectiveness of Posaconazole Versus Standard Azole Therapy in the Prevention of Invasive Fungal Infections among High-Risk Neutropenic Patients in the U.S.
O’Sullivan, AK; Pandya, A; Thompson, D; Papadopoulos, G; Weinstein, MC; Perfect, JR; Langston, A
Published in: Blood
In a recent clinical trial, posaconazole was found to be superior to standard azole therapy (i.e., fluconazole or itraconazole) in preventing both invasive fungal infections (IFIs) and in reducing overall mortality among high-risk neutropenic patients. We conducted a cost-effectiveness analysis based on trial results from a U.S. perspective. A decision-analytic model was developed to estimate the cost-effectiveness of antifungal prophylaxis among patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) at high risk of developing an IFI due to chemotherapy-induced neutropenia. To extrapolate trial results to a lifetime horizon, the model was extended with one-month Markov cycles in which mortality risk is specific to the underlying disease as estimated from SEER data. Patients in the model were assumed to receive prophylaxis with posaconazole or standard azole therapy (fluconazole, 81%; itraconazole, 19%). The probabilities of experiencing an IFI, IFI-related death, and death from other causes over 100 days of follow-up were estimated from the trial data. Long-term mortality, drug costs, and IFI treatment costs were estimated using published sources. The model was used to estimate costs, IFIs avoided, life-years gained, and the incremental cost-effectiveness of posaconazole versus standard azole therapy (using 2006 dollars). Posaconazole is associated with fewer IFIs (0.05 vs. 0.11), increased life years (0.744 vs. 0.728), and (excluding costs of the underlying condition) slightly lower costs ($4,887 vs. $5,070) per patient relative to standard azole therapy over a lifetime horizon. One-way sensitivity analyses indicate that when model parameters are varied across reasonable ranges of their base-case values, the incremental cost-effectiveness ratio for posaconazole ranges from cost saving to $50,000 per life-year saved relative to standard azole therapy. A second-order probabilistic Monte Carlo sensitivity analysis was conducted to assess the effects of parameter uncertainty on the study findings, particularly as relates to treatment efficacy and the costs of an IFI. Results indicate that there is a 75% probability that posaconazole is cost saving versus standard azole therapy and a 90% probability that the incremental cost-effectiveness ratio for posaconazole is at or below the $50,000 per life year saved threshold. Posaconazole has been shown to be more effective than standard azole therapy (i.e., fluconazole or itraconazole) in preventing IFIs and reducing overall mortality in high-risk neutropenic patients.Based on this analysis, we conclude that posaconazole is likely to be cost saving relative to standard azole therapy (i.e., fluconazole or itraconazole) in the prevention of IFIs among high-risk neutropenic patients.