Registration successful
Account activated – pending validation.
Your account has been activated successfully, but we still need to validate you as a healthcare professional. We’ll send you an email with the result of the validation process in the next three days.
In the meantime, you can enjoy access to all the latest news, events and resources for different therapy areas on our website.BPH: Immediate vs delayed initiation of combination
therapy 1
Timely treatment is important in optimising outcomes in benign prostatic hyperplasia (BPH). This study investigated the impact of starting combination therapy immediately in BPH patients at risk of disease progression, vs starting with tamsulosin monotherapy and switching to tamsulosin–dutasteride combination therapy later.
A BPH drug-disease model was used to predict IPSS trajectories in patients with moderate/severe lower urinary tract symptoms (LUTS)/BPH at risk of disease progression.
This model allowed prediction of IPSS trajectories using pooled data from 10,238 moderate to severe LUTS/BPH patients at risk of progression, in six clinical trials.
The simulations assessed the impact of early vs delayed initiation of combination therapy on disease progression and IPSS trajectories at Month 48, in seven virtual treatment arms:
- Dutasteride-tamsulosin combination therapy (COM) for 48 months
- Tamsulosin for 48 months
- Tamsulosin, switching to COM at 1 month
- Tamsulosin, switching to COM at 3 months
- Tamsulosin, switching to COM at 6 months
- Tamsulosin, switching to COM at 12 months
- Tamsulosin, switching to COM at 24 months
Primary endpoint:
- Proportion of patients achieving a clinically meaningful improvement in IPSS (≥25% reduction relative to baseline).
Secondary endpoints:
- Mean IPSS change relative to baseline.
- Proportion of patients transitioning from either severely (IPSS 20–35) or moderately (IPSS 8–19) symptomatic BPH at baseline to mildly symptomatic disease (IPSS 1–7).
- Proportion of patients achieving IPSS reductions relative to baseline of ≥35%, ≥50% and ≥75%.
Immediate initiation of combination therapy significantly increased clinical response rate* vs delayed initiation (≥6 months) at Month 48. 1
Delayed combination therapy initiation led to significant (p<0.01) decreases in clinical response, compared with early treatment initiation. The earlier that patients were switched from tamsulosin monotherapy to fixed-dose combination therapy, the better their overall treatment response.
Treatment response rate* at Month 48†.
This figure has been independently created by GSK from the original data. The same results were first published in 1. D’Agate S, et al. World J Urol 2019; https://doi.org/10.1007/s00345-019-02783-x.
*≥25% reduction from baseline in IPSS. †Log rank test for the difference versus the combination therapy group.
Predicted curves indicated that delay in initiating combination therapy resulted in a trend for lesser reduction in IPSS
Patients treated with combination therapy from Month 1 tended to have greater decreases in IPSS scores than those switched to combination therapy at a later date.
Mean IPSS change from baseline. 1
n=500 virtual patients
Mean IPSS change from baseline to month 48 was a secondary endpoint, and the study was not powered to detect a pre-defined difference between treatment arms for this endpoint. Graphical summaries and statistical analysis refer to the results of a single replicate trial.
D’Agate S, Wilson T, Adalig B, et al. World J Urol (2019) https://doi.org/10.1007/s00345-019-02783-x. Adapted with permission of the authors under a Creative Commons license (CC BY 4.0).
Predicted IPSS trajectories showed an improved trend with combination therapy vs tamsulosin monotherapy
Grey areas: predicted profiles in the absence of any active treatment. Blue areas: predicted profiles in patients receiving tamsulosin. Red areas: predicted profiles in patients receiving combination therapy. Solid lines are mean predicted IPSS, and shaded areas represent the 95% prediction interval (n=200 simulations).
D’Agate S, Wilson T, Adalig B, et al. World J Urol (2019) https://doi.org/10.1007/s00345-019-02783-x. Adapted with permission of the authors under a Creative Commons license (CC BY 4.0).
References:
- D’Agate S, et al. World J Urol 2019; https://doi.org/10.1007/s00345-019-02783-x. Accessed March 2020.
Trade marks are owned by or licensed to the GSK group of companies.
©2021 GSK group of companies or its licensor.
