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Comparative Study
. 2018 Aug 29;18(1):438.
doi: 10.1186/s12879-018-3333-0.

Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of confounding by indication

Francis Vekeman  1 , Lisa Weiss  2 , Jalal Aram  2 , Raluca Ionescu-Ittu  1 , Shahrzad Moosavi  2 , Yongling Xiao  1 , Wendy Y Cheng  1 , Rachel H Bhak  1 , Margaret Tawadrous  2 , M Rita Capparella  3 , Philippe Montravers  4 , Mei Sheng Duh  5   6
Affiliations
Comparative Study

Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of confounding by indication

Francis Vekeman et al. BMC Infect Dis. .

Abstract

Background: To compare the risk of severe hepatotoxicity with anidulafungin versus caspofungin and micafungin in hospitalized adults.

Methods: This retrospective cohort study combined data from two large US- based hospital electronic medical record databases. Severe hepatotoxicity was a Grade ≥ 3 liver function test (LFT) post-echinocandin initiation. Adjusted incidence rate ratios (IRRs) were estimated for anidulafungin versus caspofungin and micafungin, overall and in patients with normal baseline LFT (Grade 0).

Results: Treatments included anidulafungin (n = 1700), caspofungin (n = 4431), or micafungin (n = 6547). The proportions with LFT Grade ≥ 3 pre-echinocandin initiation were: anidulafungin 40.4% versus caspofungin 25.9% (p < 0.001) and micafungin 25.6% (p < 0.001). Rates of severe underlying diseases or comorbidities were: critical care admissions: 75.3% versus 52.6 and 48.6%; and organ failures: 69.4% versus 46.7 and 51.5%. Adjusted IRRs of severe hepatotoxicity for anidulafungin versus caspofungin and micafungin were 1.43 (p = 0.002) and 1.19 (p = 0.183) overall, and 0.88 (P = 0.773) and 0.97 (P = 0.945) for normal baseline LFT, respectively.

Conclusions: Accounting for confounders, severe hepatotoxicity risk was not significantly different across echinocandins in this real-world head-to-head study. Anidulafungin was used more frequently in patients with more comorbidities. Those with normal baseline LFT (least susceptible to confounding by indication), showed no elevated hepatotoxicity risk for anidulafungin.

Keywords: Anidulafungin; Caspofungin; Echinocandin; Micafungin; Severe hepatotoxicity.

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Conflict of interest statement

Ethics approval and consent to participate

Ethics approval was obtained from the New England Institutional Review Board, Newton, MA. The data used in this study were de-identified and obtained from commercial sources. As a result, no administrative permission was required for this study.

Consent for publication

Not applicable.

Competing interests

RII, WYC, RHB, and MSD are employees of Analysis Group, Inc., a consulting company, which received financial support from Pfizer in connection with this study. FV and YX were employees of the Analysis Group, Inc. at the time the study was completed. LW, JA, SM, MRC, and MT are employees of, and may hold stock in, Pfizer. PM lectures and/or participates in advisory boards for Astellas, AstraZeneca, Basilea, Cubist, Gilead, MSD, Parexel, Pfizer, Tetraphase, and The Medicines Company.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

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Fig. 1
Study population selection flowchart
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