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
(2022) In European Urology 81(3). p.285-293- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2022-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Androgen deprivation therapy, Antiandrogen, Bicalutamide, COVID-19, Enzalutamide, Randomized trial, SARS-CoV-2
- in
- European Urology
- volume
- 81
- issue
- 3
- pages
- 9 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85122412349
- pmid:35168845
- ISSN
- 0302-2838
- DOI
- 10.1016/j.eururo.2021.12.013
- language
- English
- LU publication?
- yes
- id
- b3ada59b-fc2f-4075-90f4-a8e7b2e9002f
- date added to LUP
- 2022-12-28 14:29:06
- date last changed
- 2024-06-13 22:28:20
@article{b3ada59b-fc2f-4075-90f4-a8e7b2e9002f,
abstract = {{<p>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.</p>}},
author = {{Welén, Karin and Rosendal, Ebba and Gisslén, Magnus and Lenman, Annasara and Freyhult, Eva and Fonseca-Rodríguez, Osvaldo and Bremell, Daniel and Stranne, Johan and Balkhed, Åse Östholm and Niward, Katarina and Repo, Johanna and Robinsson, David and Henningsson, Anna J. and Styrke, Johan and Angelin, Martin and Lindquist, Elisabeth and Allard, Annika and Becker, Miriam and Rudolfsson, Stina and Buckland, Robert and Carlsson, Camilla Thellenberg and Bjartell, Anders and Nilsson, Anna C. and Ahlm, Clas and Connolly, Anne Marie Fors and Överby, Anna K. and Josefsson, Andreas}},
issn = {{0302-2838}},
keywords = {{Androgen deprivation therapy; Antiandrogen; Bicalutamide; COVID-19; Enzalutamide; Randomized trial; SARS-CoV-2}},
language = {{eng}},
number = {{3}},
pages = {{285--293}},
publisher = {{Elsevier}},
series = {{European Urology}},
title = {{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}},
url = {{http://dx.doi.org/10.1016/j.eururo.2021.12.013}},
doi = {{10.1016/j.eururo.2021.12.013}},
volume = {{81}},
year = {{2022}},
}