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.
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.
An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline IPSS, PSA, 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.
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 (symptomatic treatment) has no impact on individual long-term risk.
British journal of clinical pharmacology. 2020 Nov 28 [Epub ahead of print]
Salvatore D'Agate, Chandrashekhar Chavan, Michael Manyak, Juan Manuel Palacios-Moreno, Matthias Oelke, Martin C Michel, Claus G Roehrborn, Oscar Della Pasqua
Clinical Pharmacology & Therapeutics Group, University College London, BMA House, Tavistock Square, London, WC1H 9JP, UK., Global Medical Urology, GlaxoSmithKline, 23rd Rd, Seepz, Mumbai, Maharashtra, 400093, India., Global Medical Urology, GlaxoSmithKline, 2322 Blaine Dr, Chevy Chase, MD, 20815, USA., Global Medical Urology, GlaxoSmithKline, Calle de Severo Ochoa, 2, 28760, Tres Cantos, Spain., Department of Urology, St. Antonius Hospital, Möllenweg 22, D-48599, Gronau, Germany., Department of Pharmacology, Johannes Gutenberg University, Langenbeckstraße 1, 55131, Mainz, Germany., Department of Urology, Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.