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.

Objective: To evaluate real-world persistence and adherence in patients with benign prostate hyperplasia (BPH) receiving a fixed-dose combination of dutasteride plus tamsulosin (DUT-TAM FDC) versus α-blocker plus 5-α reductase inhibitor (AB/5ARI) free-combination therapy. Materials and methods: This retrospective, observational cohort study utilized the German IMS LRx (IQVIA) database. Patients ≥ 45 years old with BPH receiving DUT-TAM FDC or AB/5ARI free-combination therapy from July 1, 2011 to November 30, 2017 were included. Data were analyzed for 48 months from index date (date of first prescription). Persistence, measured as time to discontinuation (defined as a 90-day gap in therapy), was evaluated using Kaplan-Meier curves (log-rank tests). Adherence, measured as medication possession ratio (MPR), was based on a comparison of mean prescribing duration and expected treatment duration. Results: A total of 141,667 patients were included (DUT-TAM FDC, n = 86,057; free AB/5ARI: n = 55,610). Small differences in persistence were observed between treatment arms. At month 12, 41.8% of DUT-TAM FDC-treated and 41.0% of AB/5ARI free-combination therapy-treated patients were persistent; at month 24, 28.2% and 27.1% were persistent, respectively. A higher proportion of DUT-TAM FDC-treated patients had MPR ≥ 0.80, ≥ 0.75 and ≥ 0.70 compared with AB/5ARI free-combination therapy (p < 0.0001). Conclusion: Small differences observed in persistence between treatment arms may not translate to meaningful clinical relevance. Adherence was significantly better in the FDC arm, which may be clinically relevant as improved adherence is associated with better outcomes. Persistence and adherence to BPH therapy in Germany is low; further studies exploring the reasons behind this are required.

SummaryAimTo assess attitudes and beliefs towards benign prostatic hyperplasia (BPH)/ lower urinary tract symptoms (LUTS) and its treatment among patients and physicians in Latin America, Asia Pacific and the Commonwealth of Independent States (CIS).MethodsCross‐sectional, quantitative study conducted between December 2014 and September 2015. Separate questionnaires were administered to BPH/LUTS patients receiving drug treatment for their condition and to practising physicians who treat patients with BPH/LUTS.ResultsIn total, 1094 patients and 202 physicians completed a questionnaire. Most patients (61%) felt very/fairly well informed about BPH/LUTS, and 60% of physicians perceived patients to be very/somewhat informed. Overall, 70% of physicians felt that it would be valuable to raise awareness of BPH/LUTS and encourage men to consult a physician. The first symptoms most commonly noticed by patients were need to urinate more frequently, slower/weaker stream and nocturia. At first consultation, 71% of patients recalled providing a urine sample, 57% having a blood test for prostate‐specific antigen and 56% a digital rectal examination being performed. Over two thirds of patients (69%) were satisfied with their current medication; highest satisfaction rates (among both patients and physicians) were reported for alpha blockers and 5ARIs, either as monotherapies or used in combination. Patients were prepared to wait longer for symptom relief in order to have a reduced risk of surgery. Most physicians (90%) thought that at least some patients believe BPH/LUTS to be a progressive condition. Most physicians thought that patients were very/fairly concerned about BPH surgery (92%) and acute urinary retention (72%); 52% of physicians thought treatment adherence was “extremely” important.ConclusionsThis study provides valuable insights into the attitudes and beliefs of patients and physicians in Asia Pacific, Latin America and CIS about BPH/LUTS and its management. It also highlights areas of discordance between patient/physician perceptions and beliefs about BPH/LUTS, and potential areas of focus to improve the experience of affected patients.

Aims: International Prostate Symptom Score (IPSS) is a marker of lower urinary tract symptoms (LUTS) deterioration or improvement in benign prostate hyperplasia (BPH). Whereas changes in IPSS relative to baseline have been used as endpoints in clinical trials, little attention has been given to the time course of symptoms. The current investigation aimed to develop a drug-disease model to describe individual IPSS trajectories in moderate and severe BPH patients. Methods: A model-based meta-analytical approach was used including data from 10 238 patients enrolled into Phase III and IV studies receiving placebo, tamsulosin, dutasteride or combination therapy over a period of up to 4 years. Model predictive performance was assessed using statistical and graphical criteria. Subsequently, simulations were performed to illustrate the implications of treatment with drugs showing symptomatic and disease-modifying properties in patients with varying disease progression rates.Results: Improvement and worsening of IPSS could be characterized by a model including a sigmoid function which disentangles drug effects from placebo and varying disease progression rates on IPSS. Mean estimate (95% confidence intervals) for the disease progression rate was 0.319 (0.271-0.411) month −1 . Treatment effect on IPSS (DELTA) was found to be 0.0605, 0.0139 and 0.0310 month −1 for placebo, tamsulosin and combination therapy, respectively. In addition, it appears that individual trajectories can be clustered together into different phenotypes describing the underlying disease progression rate (i.e. slow, moderate and fast progressors). Conclusions:The availability of a drug-disease model enables the evaluation of interindividual differences in disease progression rate, deterioration of symptoms and treatment effects on LUTS/BPH.

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