TY - JOUR
T1 - A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome
T2 - No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
AU - Welén, Karin
AU - Rosendal, Ebba
AU - Gisslén, Magnus
AU - Lenman, Annasara
AU - Freyhult, Eva
AU - Fonseca-Rodríguez, Osvaldo
AU - Bremell, Daniel
AU - Stranne, Johan
AU - Balkhed, Åse Östholm
AU - Niward, Katarina
AU - Repo, Johanna
AU - Robinsson, David
AU - Henningsson, Anna J.
AU - Styrke, Johan
AU - Angelin, Martin
AU - Lindquist, Elisabeth
AU - Allard, Annika
AU - Becker, Miriam
AU - Rudolfsson, Stina
AU - Buckland, Robert
AU - Carlsson, Camilla Thellenberg
AU - Bjartell, Anders
AU - Nilsson, Anna C.
AU - Ahlm, Clas
AU - Connolly, Anne Marie Fors
AU - Överby, Anna K.
AU - Josefsson, Andreas
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - Androgen deprivation therapy
KW - Antiandrogen
KW - Bicalutamide
KW - COVID-19
KW - Enzalutamide
KW - Randomized trial
KW - SARS-CoV-2
U2 - 10.1016/j.eururo.2021.12.013
DO - 10.1016/j.eururo.2021.12.013
M3 - Article
C2 - 35168845
AN - SCOPUS:85122412349
SN - 0302-2838
VL - 81
SP - 285
EP - 293
JO - European Urology
JF - European Urology
IS - 3
ER -
