Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH

Salvatore D’Agate, Timothy Wilson, Burkay Adalig, Michael Manyak, Juan Manuel Palacios-Moreno, Chandrashekhar Chavan, Matthias Oelke, Claus Roehrborn, Oscar Della Pasqua

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
JournalWorld Journal of Urology
DOIs
StatePublished - Jan 1 2019

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Disease Progression
Prostate
tamsulosin
Therapeutics
Lower Urinary Tract Symptoms
Prostatic Hyperplasia
Clinical Trials
Complementary Therapies

Keywords

  • Benign prostatic hyperplasia
  • Clinical trial simulation
  • Drug–disease modelling
  • Dutasteride
  • Lower urinary tract symptoms
  • Tamsulosin

ASJC Scopus subject areas

  • Urology

Cite this

Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH. / D’Agate, Salvatore; Wilson, Timothy; Adalig, Burkay; Manyak, Michael; Palacios-Moreno, Juan Manuel; Chavan, Chandrashekhar; Oelke, Matthias; Roehrborn, Claus; Della Pasqua, Oscar.

In: World Journal of Urology, 01.01.2019.

Research output: Contribution to journalArticle

D’Agate, Salvatore ; Wilson, Timothy ; Adalig, Burkay ; Manyak, Michael ; Palacios-Moreno, Juan Manuel ; Chavan, Chandrashekhar ; Oelke, Matthias ; Roehrborn, Claus ; Della Pasqua, Oscar. / Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH. In: World Journal of Urology. 2019.
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abstract = "Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.",
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AU - Wilson, Timothy

AU - Adalig, Burkay

AU - Manyak, Michael

AU - Palacios-Moreno, Juan Manuel

AU - Chavan, Chandrashekhar

AU - Oelke, Matthias

AU - Roehrborn, Claus

AU - Della Pasqua, Oscar

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AB - Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

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KW - Dutasteride

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KW - Tamsulosin

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