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

M Hong Nguyen; Luis Ostrosky-Zeichner; Peter G Pappas; Thomas J Walsh; Joseph Bubalo; Barbara D Alexander; Marisa H Miceli; Jeanette Jiang; Yi Song; George R Thompson 3rd

doi:10.1093/ofid/ofad424

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

Open Forum Infect Dis. 2023 Aug 7;10(9):ofad424. doi: 10.1093/ofid/ofad424. eCollection 2023 Sep.

Authors

Affiliations

¹ University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
² McGovern Medical School, Houston, Texas, USA.
³ University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Weill Cornell Medicine, Cornell University, New York, New York, USA.
⁵ Institute for Innovative Therapeutics and Diagnostics, Richmond, Virginia, USA.
⁶ Oregon Health and Science University Hospital and Clinics, Portland, Oregon, USA.
⁷ Duke University, Durham, North Carolina, USA.
⁸ University of Michigan, Ann Arbor, Michigan, USA.
⁹ Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA.
¹⁰ UC Davis Health, Sacramento, California, USA.

Abstract

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.

Keywords: antifungal prophylaxis; isavuconazole; posaconazole; real-world; voriconazole.