Real-world Use of Mold-Active Triazole Prophylaxis in the Prevention of Invasive Fungal Diseases: Results From a Subgroup Analysis of a Multicenter National Registry.

Background: Antifungal prophylaxis can prevent invasive fungal diseases (IFDs) in high-risk, immunocompromised patients. This study assessed the real-world use of mold-active triazoles (MATs) for the prevention of IFDs.
Methods: This subgroup analysis of a multicenter, observational, prospective registry in the United States from March 2017 to April 2020 included patients who received MATs for prophylaxis (isavuconazole, posaconazole, and voriconazole) at study index/enrollment. The primary objective was to describe patient characteristics and patterns of MAT use. Exploratory assessments included the frequency of breakthrough IFDs and MAT-related adverse drug reactions (ADRs).
Results: A total of 1177 patients (256 isavuconazole, 397 posaconazole, 272 voriconazole, and 252 multiple/sequenced MATs at/after index/enrollment) were included in the prophylaxis subgroup analysis. Patient characteristics were similar across MAT groups, but risk factors varied. Hematological malignancy predominated (76.5%) across all groups. Breakthrough IFDs occurred in 7.1% (73/1030) of patients with an investigator's assessment (5.0% [11/221] isavuconazole; 5.3% [20/374] posaconazole; 4.0% [9/226] voriconazole; and 15.8% [33/209] multiple/sequenced MATs). Aspergillus (29.5% [18/61]) and Candida (36.1% [22/61]) species were the most common breakthrough pathogens recovered. ADRs were reported in 14.1% of patients, and discontinuation of MATs due to ADRs was reported in 11.1% of patients (2.0% [5/245] isavuconazole; 8.2% [30/368] posaconazole; and 10.1% [27/267] voriconazole).
Conclusions: Breakthrough IFDs were uncommon in patients who received MATs for prophylaxis. Candida and Aspergillus species were the most commonly reported breakthrough pathogens. The discontinuation of MATs due to ADRs was infrequent. These findings support prophylactic strategies with isavuconazole, posaconazole, and voriconazole in high-risk patients.
Competing Interests: Potential conflicts of interest. M.H.N. reports grants from Astellas Pharma Global Development, Inc., Scynexis, Mayne Pharma, Pulmocide, and T2 Biosystems and serves as consultant to T2 Biosystems and MiraVista. L.O.Z. reports grants from Gilead, Pfizer, Scynexis, Cidara, and Pulmocide; payment or honoraria from Pfizer and F2G; and participation on boards for Cidara, F2G, Pfizer, Eurofins, and Appili. P.G.P. reports grants from Scynexis, Mayne Pharma, Astellas, and Cidara and consulting fees from F2G, Matinas, and Cidara. T.J.W. reports grants for experimental and clinical antimicrobial pharmacology, therapeutics, and diagnostics to his institution from Allergan, Amplyx, Astellas, Lediant, Merck, The Medicines Company, Scynexis, Shionogi, T2 Biosystems, Tetraphase, and Viosera and has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Karyopharm, Leadiant, The Medicines Company, Merck, Methylgene, Partner Therapeutics, Pfizer, Scynexis, Shionogi, Statera, and T2 Biosystems. J.B. reports payment or honoraria from medSynergy and participation on an advisory board for Pfizer. B.D.A. reports grants from Leadiant; royalties from UpToDate; participation on advisory boards for HealthTrackRx, Merck, and ThermoFisher; leadership or fiduciary roles on other boards for the IDSA; and acting as principal investigator for clinical trial sites for F2G, Scynexis, Cidara, and Shire/Takeda. M.H.M. reports grants and consulting fees from Astellas; grants from F2G and Scynexis; and consulting fees from Scynexis and PSI. J.J. and Y.S. are/were employees of Astellas Pharma Global Development, Inc. G.R.T. has nothing to disclose.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)