TY - JOUR
T1 - Impact of early vs. delayed initiation of dutasteride/tamsulosin combination therapy on the risk of acute urinary retention or BPH-related surgery in LUTS/BPH patients with moderate-to-severe symptoms at risk of disease progression
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 - Publisher Copyright:
© 2020, The Author(s).
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. Methods: Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1–24 months). AUR/S incidence was described by Kaplan–Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. Results: Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively. Conclusions: Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.
AB - Purpose: To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. Methods: Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1–24 months). AUR/S incidence was described by Kaplan–Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. Results: Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively. Conclusions: Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.
KW - Acute urinary retention
KW - BPH-related surgery
KW - Benign prostatic hyperplasia
KW - Clinical trial simulations
KW - Dutasteride
KW - Lower urinary tract symptoms
KW - Relative risk
KW - Tamsulosin
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U2 - 10.1007/s00345-020-03517-0
DO - 10.1007/s00345-020-03517-0
M3 - Article
C2 - 33337513
AN - SCOPUS:85097732294
SN - 0724-4983
VL - 39
SP - 2635
EP - 2643
JO - World journal of urology
JF - World journal of urology
IS - 7
ER -