Despite superiority of tamsulosin-dutasteride combination therapy versus monotherapy for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH), patients at risk of disease progression are often initiated on α-blockers. This study evaluated the impact of initiating tamsulosin monotherapy prior to switching to tamsulosin-dutasteride combination therapy versus immediate combination therapy using a longitudinal model describing International Prostate Symptom Score (IPSS) trajectories in moderate/severe LUTS/BPH patients at risk of disease progression.
Clinical trial simulations (CTS) were performed using data from 10,238 patients from Phase III/IV dutasteride trials. The effect of varying disease progression rates was explored by comparing profiles on- and off-treatment. CTS scenarios were investigated, including a reference (immediate combination therapy) and six alternative virtual treatment arms (delayed combination therapy of 1-24 months). Clinical response (≥ 25% IPSS reduction relative to baseline) was analysed using log-rank test. Differences in IPSS relative to baseline at various on-treatment time points were assessed by t tests.
Delayed combination therapy initiation led to significant (p < 0.01) decreases in clinical response. At month 48, clinical response rate was 79.7% versus 74.1%, 70.3% and 71.0% and IPSS was 6.3 versus 7.6, 8.1 and 8.0 (switchers from tamsulosin monotherapy after 6, 12 and 24 months, respectively) with immediate combination therapy. More patients transitioned from severe/moderate to mild severity scores by month 48.
CTS allows systematic evaluation of immediate versus delayed combination therapy. Immediate response to α-blockers is not predictive of long-term symptom improvement. Observed IPSS differences between immediate and delayed combination therapy (6-24 months) are statistically significant.
World journal of urology. 2019 May 11 [Epub ahead of print]
Salvatore D'Agate, Timothy Wilson, Burkay Adalig, Michael Manyak, Juan Manuel Palacios-Moreno, Chandrashekhar Chavan, Matthias Oelke, Claus Roehrborn, Oscar Della Pasqua
Clinical Pharmacology and Therapeutics Group, University College London, London, UK., PAREXEL International, Durham, NC, USA., Classic and Established Products, GSK, Istanbul, Turkey., Classic and Established Products, GSK, Washington, DC, USA., Classic and Established Products, GSK, Madrid, Spain., Classic and Established Products, GSK, Worli, Mumbai, India., Department of Urology, St. Antonius Hospital, Gronau, Germany., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Clinical Pharmacology and Therapeutics Group, University College London, London, UK. .