A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data.
Aged
Aged, 80 and over
Androgen Antagonists
/ therapeutic use
Androgens
/ therapeutic use
Anilides
/ therapeutic use
Benzamides
/ therapeutic use
COVID-19
/ diagnosis
COVID-19 Nucleic Acid Testing
Female
Hospitalization
Humans
Male
Middle Aged
Nitriles
/ therapeutic use
Phenylthiohydantoin
/ therapeutic use
Retrospective Studies
SARS-CoV-2
/ isolation & purification
Sweden
/ epidemiology
Testosterone
Tosyl Compounds
/ therapeutic use
Treatment Outcome
COVID-19 Drug Treatment
Androgen deprivation therapy
Antiandrogen
Bicalutamide
COVID-19
Enzalutamide
Randomized trial
SARS-CoV-2
Journal
European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
07
09
2021
revised:
22
11
2021
accepted:
07
12
2021
pubmed:
5
1
2022
medline:
9
3
2022
entrez:
4
1
2022
Statut:
ppublish
Résumé
Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2-positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20-0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52-4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
Sections du résumé
BACKGROUND
Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.
OBJECTIVE
To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.
DESIGNS, SETTINGS, AND PARTICIPANTS
A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2-positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.
INTERVENTION
In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.
OUTCOME MEASUREMENTS
The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.
RESULTS AND LIMITATIONS
Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20-0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52-4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.
CONCLUSIONS
The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.
PATIENT SUMMARY
We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
Identifiants
pubmed: 34980495
pii: S0302-2838(21)02224-7
doi: 10.1016/j.eururo.2021.12.013
pmc: PMC8673828
pii:
doi:
Substances chimiques
Androgen Antagonists
0
Androgens
0
Anilides
0
Benzamides
0
Nitriles
0
Tosyl Compounds
0
Phenylthiohydantoin
2010-15-3
Testosterone
3XMK78S47O
enzalutamide
93T0T9GKNU
bicalutamide
A0Z3NAU9DP
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
285-293Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
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