Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals

Sebastian Schneeweiss, Peggy L. Carver, Kausik Datta, Alicia Galar, Melissa D. Johnson, Alyssa R. Letourneau, Francisco M. Marty, Jerod Nagel, Maryann Najdzinowicz, Melissa Saul, Mindy Schuster, Shmuel Shoham, Fernanda P. Silveira, Christy Varughese, Marissa Wilck, Lisa Weatherby, Joop van Oene, Alexander M. Walker

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.

Original languageEnglish (US)
Pages (from-to)221-228
Number of pages8
JournalThe Journal of antimicrobial chemotherapy
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2020

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Hepatocellular Carcinoma
Mortality
Propensity Score
Drug Labeling
micafungin
Electronic Health Records
Liver

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals. / Schneeweiss, Sebastian; Carver, Peggy L.; Datta, Kausik; Galar, Alicia; Johnson, Melissa D.; Letourneau, Alyssa R.; Marty, Francisco M.; Nagel, Jerod; Najdzinowicz, Maryann; Saul, Melissa; Schuster, Mindy; Shoham, Shmuel; Silveira, Fernanda P.; Varughese, Christy; Wilck, Marissa; Weatherby, Lisa; Oene, Joop van; Walker, Alexander M.

In: The Journal of antimicrobial chemotherapy, Vol. 75, No. 1, 01.01.2020, p. 221-228.

Research output: Contribution to journalArticle

Schneeweiss, S, Carver, PL, Datta, K, Galar, A, Johnson, MD, Letourneau, AR, Marty, FM, Nagel, J, Najdzinowicz, M, Saul, M, Schuster, M, Shoham, S, Silveira, FP, Varughese, C, Wilck, M, Weatherby, L, Oene, JV & Walker, AM 2020, 'Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals', The Journal of antimicrobial chemotherapy, vol. 75, no. 1, pp. 221-228. https://doi.org/10.1093/jac/dkz396
Schneeweiss, Sebastian ; Carver, Peggy L. ; Datta, Kausik ; Galar, Alicia ; Johnson, Melissa D. ; Letourneau, Alyssa R. ; Marty, Francisco M. ; Nagel, Jerod ; Najdzinowicz, Maryann ; Saul, Melissa ; Schuster, Mindy ; Shoham, Shmuel ; Silveira, Fernanda P. ; Varughese, Christy ; Wilck, Marissa ; Weatherby, Lisa ; Oene, Joop van ; Walker, Alexander M. / Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals. In: The Journal of antimicrobial chemotherapy. 2020 ; Vol. 75, No. 1. pp. 221-228.
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abstract = "BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95{\%} CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87{\%} of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95{\%} CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.",
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T1 - Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals

AU - Schneeweiss, Sebastian

AU - Carver, Peggy L.

AU - Datta, Kausik

AU - Galar, Alicia

AU - Johnson, Melissa D.

AU - Letourneau, Alyssa R.

AU - Marty, Francisco M.

AU - Nagel, Jerod

AU - Najdzinowicz, Maryann

AU - Saul, Melissa

AU - Schuster, Mindy

AU - Shoham, Shmuel

AU - Silveira, Fernanda P.

AU - Varughese, Christy

AU - Wilck, Marissa

AU - Weatherby, Lisa

AU - Oene, Joop van

AU - Walker, Alexander M.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.

AB - BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.

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