TY - JOUR
T1 - Model-based meta-analysis of the time to first acute urinary retention or benign prostatic hyperplasia-related surgery in patients with moderate or severe symptoms
AU - D'Agate, Salvatore
AU - Chavan, Chandrashekhar
AU - Manyak, Michael
AU - Palacios-Moreno, Juan Manuel
AU - Oelke, Matthias
AU - Michel, Martin C.
AU - Roehrborn, Claus G.
AU - Della Pasqua, Oscar
N1 - Funding Information:
This investigation was funded by GlaxoSmithKline (GSK).
Funding Information:
S.D.A. none to declare. M.O. has been a speaker, consultant and/or trial investigator for Apogepha, Astellas, Ferring, GSK, Pierre Fabre and Pfizer, and received research grants from Astellas and Pfizer. M.C.M. has been a speaker and consultant for Apogepha, Astellas, Dr. Willmar Schwabe, Ferring, GSK, Recordati and Velicept, and is a past employee of Boehringer Ingelheim and a current shareholder of Velicept. C.G.R. was previously employed as a consultant for GSK. C.C., M.M., J.M.P.M. and O.D.P. are GSK employees and hold stocks/shares in GSK.
PY - 2020
Y1 - 2020
N2 - Aims: Combination therapy of 5α-reductase inhibitor and α-blocker is a guideline-endorsed therapeutic approach for patients with moderate-to-severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH-related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease-modifying properties. Methods: A time-to-event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin-dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods. Results: An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate-specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin-dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo. Conclusions: Our analysis showed the implications of disease-modifying properties of dutasteride and tamsulosin-dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long-term risk.
AB - Aims: Combination therapy of 5α-reductase inhibitor and α-blocker is a guideline-endorsed therapeutic approach for patients with moderate-to-severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH-related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease-modifying properties. Methods: A time-to-event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin-dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods. Results: An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate-specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin-dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo. Conclusions: Our analysis showed the implications of disease-modifying properties of dutasteride and tamsulosin-dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long-term risk.
KW - acute urinary retention
KW - baseline risk factors
KW - benign prostatic hyperplasia
KW - disease-modifying properties
KW - dutasteride
KW - lower urinary tract symptoms
KW - tamsulosin
KW - time-to-event modelling
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U2 - 10.1111/bcp.14682
DO - 10.1111/bcp.14682
M3 - Article
C2 - 33247951
AN - SCOPUS:85099465025
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
SN - 0306-5251
ER -