Empirical Versus Pre-Emptive Antifungal Therapy in High-Risk Febrile Neutropenic Patients: An Economic Analysis.
Authors: Schwarzinger Michael , Beauchamp Celine , Maury Sebastien , Pautas Cecile , Vekhoff Anne , Farhat Hassan , Suarez Felipe , Hemery François , Kuentz Mathieu , Maison Patrick , Cordonnier Catherine 
Published: October 2019

Abstract
Empirical (E) antifungal therapy (ATF) is a standard of care in neutropenic patients with persistent or recurrent fever. However, the safety and cost-effectiveness of the E strategy are challenged by the development of better diagnostic methods and more effective therapies for invasive fungal infection (IFI). An economic analysis was conducted alongside a multicenter open-label randomized non-inferiority trial showing that a pre-emptive (PE) strategy based on clinical symptoms and GM Ag did not reduce the overall survival of prolonged neutropenic patients when compared to a E strategy (details provided in abstract 551005).
Objective: The objective of the study was to compare hospital costs between the PE strategy and E strategy.
Patients: 293 adult patients with hematologic malignancies and an expected neutropenia (<500 PMN) of ≥ 10 days following chemotherapy were randomized between E or PE strategy with polyens. All were screened 2/w for GM Ag. E patients were given ATFs in case of persistent or recurrent fever, whatever the accompanying symptoms, while PE patients were given ATFs only in case of pneumonia, severe mucositis, septic shock, sinusitis, or skin lesions evocative of filamentous infection, aspergillus colonization, or positive GM Ag.
Methods: The economic analysis was conducted from the hospital perspective (€2005). Total medication costs were computed from individual records during hospital stay.
Results: Overall, mean medication costs did not differ significantly between the PE and E groups (see Table). In patients in induction phase (n=151), mean medication costs were higher in the PE group than the E group (+921€, [95%CI, −1602 to +3444]) as explained by the significantly higher proportion of IFI in the PE group (16.4% vs. 3.9%, p<0.01) and the significantly higher medication costs in case of IFI (+4224€, [95%CI, +1200 to +7244]). In patients in consolidation phase (n=51) or autologous stem cell transplant (ASCT) (n=91), mean medication costs were significantly lower in the PE group than the E group (−1224€, [95%CI, −233 to −2215]) as explained by the significantly lower proportion of patients receiving ATF in the PE group (31% vs. 50%, p<0.03).
Conclusion: Cost comparison between E and PE strategy showed opposite results in induction or consolidation/ASCT phases. This finding is mainly explained by different risks of developing IFI according to the therapeutic phase. (Grants: PRC 2002 AOR02028).
Table: Comparison of mean(std) medication costs, antifungal therapy costs, and proportion of IFI between PE and E groups (€2005) PE strategy E strategy p Overall (n=293) Medication costs 3595 (7444), n=143 3745 (4768), n=150 ns Antifungal therapy costs 2218 (6969), n=143 2337(4093), n=150 ns Proportion of IFI 9.1% (13/143) 2.7% (4/150) <0.02 Induction (n=151) Medication costs 5714 (9843), n=73 4793 (5330), n=78 ns Antifungal therapy costs 3974 (9360, n=73 3353 (4876), n=78 ns Proportion of IFI 16.4% (12/73) 3.9% (3/78) <0.01 Consolidation or ASCT (n=142) Medication costs 13871807, n=70 2610 (3795), n=72 <0.02 Antifungal therapy costs 386 (1367), n=70 1237 (2649), n=72 <0.02 Proportion of IFI 1.4% (1/70) 1.4% (1/72) ns