Abstract
PurposeDespite 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.MethodsClinical 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.ResultsDelayed 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.ConclusionsCTS 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.
Highlights
The primary treatment goal for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/ BPH) is to reduce bothersome symptoms, with clinical management focused on altering disease progression and preventing long-term complications such as surgery or acute urinary retention (AUR) [1,2,3]
The 4-year Combination of Avodart and Tamsulosin (CombAT) study showed that the dutasteride–tamsulosin combination was more effective than tamsulosin monotherapy in reducing the relative risk of AUR, BPH-related surgery, and BPH clinical progression in men with moderate-tosevere LUTS at increased risk of progression [7]
These findings support the use of clinical trial simulations (CTS) based on individual International Prostate Symptom Score (IPSS) trajectories to assess the deterioration of symptoms associated with varying rates of disease progression and evaluate the effect of early versus delayed onset of combination therapy with the tamsulosin and dutasteride
Summary
The primary treatment goal for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/ BPH) is to reduce bothersome symptoms, with clinical management focused on altering disease progression and preventing long-term complications such as surgery or acute urinary retention (AUR) [1,2,3]. Treatment guidelines for patients at risk of progression centre on two drug classes: 5α-reductase inhibitors (5-ARI) and α-blockers [4]. These recommendations are supported by data from large clinical studies, which indicate a significant reduction in risk of AUR and BPH-related surgery in patients treated with combination therapy [5, 6]. Delaying combination therapy may reduce long-term benefits due to the absence of a disease-modifying moiety in the initial treatment phase
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
