Healthcare resource utilization and cost among males with lower urinary tract symptoms with a predominant storage component in Spain: The epidemiological, cross-sectional MERCURY study.

AIMS: To assess the relationship between storage-predominant LUTS and healthcare resource consumption and cost among males in Spain. METHODS: In this non-interventional, cross-sectional study, urologists enrolled males with storage-predominant LUTS and recorded the consumption of healthcare resources (medical visits, diagnostic tests/monitoring, treatment, and hospitalizations) within the previous 6 months. The cost of healthcare resources was calculated from unit costs extracted from a Spanish eHealth database. Severity of LUTS was assessed by the Bladder Self-Assessment Questionnaire (BSAQ) and patients were stratified by symptom score (<6 or ≥6) to assess the relationship between LUTS severity and healthcare resource consumption and cost. RESULTS: Among 610 enrolled patients (BSAQ symptom score <6, n = 191; BSAQ symptom score ≥6, n = 419), the majority (87.7%) consumed healthcare resources during the previous 6 months in the form of medical visits (86.2%), diagnostic tests/monitoring (83.4%), and treatment (85.9%). Patients with BSAQ symptom scores ≥6 used more healthcare resources compared with patients with BSAQ symptom scores <6. The most common treatments for LUTS were α-blockers used as monotherapy (n = 229 [37.5%]) or in combination with antimuscarinics (n = 227 [37.2%]). The estimated median annual cost was €1070 per patient, consisting of diagnostic tests/monitoring (54.6%), medical visits (20.5%), and treatment (29.6%), and was higher in patients with BSAQ symptom score ≥6 (€1127) than in patients with BSAQ symptom score <6 (€920; P < 0.001). CONCLUSIONS: More severe LUTS are associated with higher healthcare consumption and cost. These findings highlight the importance of symptom management in LUTS patients to help minimize healthcare consumption and cost.

Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC).

To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001-September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator's choice of carbo). Analyses examined comparative efficacy by hazard ratio (HR) for overall survival (OS), and progression-free survival (PFS), and odds ratio (OR) for overall response rate (ORR), with 1L regimens vs. SOC. SOC was gemcitabine + cis (GemCis) or carboplatin (GemCarbo), cis-eligible/mixed network, and GemCarbo cis-ineligible networks. Of 1906 SLR identified citations, 55 trials were selected for data extraction. The NMA comprised 11, 6, and 8 studies in the cis-eligible/mixed, cis-ineligible (strict), cis-ineligible (wide) networks, respectively. In a meta-analysis of SOC control arms, median (95% CI) overall survival (OS) in months varied by network: 13.19 (12.43, 13.95) cis-eligible/mixed, 11.96 (10.43, 13.48) cis-ineligible (wide), and 9.74 (6.71, 12.76) cis-ineligible (strict). Most differences in OS, PFS, and ORR with treatment regimens across treatment networks were not statistically significant compared with SOC. Outcomes with current 1L regimens remain poor, and few significant improvements over SOC have been made, despite inclusion of recent clinical trial data, highlighting an unmet need in the la/mUC patient population.

Benchmarking Maintenance Therapy Survival in First-Line Platinum-Based Chemotherapy-Treated Patients with Advanced Urothelial Carcinoma Using Simulated Disease Modeling.

Objective: First-line (1L) maintenance avelumab prolonged overall survival (OS) in patients with advanced urothelial carcinoma (aUC) in JAVELIN Bladder 100. OS was measured from maintenance initiation in patients with disease control following 1L platinum-based therapy (PBT). The OS impact of maintenance for the 1L PBT-treated population is unknown since it was not measured from 1L initiation, nor can it be benchmarked with other 1L therapies. To characterize the OS impact of maintenance avelumab, we used an oncology simulation model to estimate the OS of maintenance-eligible and -ineligible patients with aUC from 1L PBT initiation. Methods: We developed a simulated cohort of 1L PBT-treated patients with aUC, including those who did and did not receive maintenance avelumab. Eligibility was assessed at 5.6 months post 1L PBT initiation based on the JAVELIN trial design. Among the 1L-treated population, 58% (95% credible interval [CrI] 49-67%) were projected to be eligible (calculated from contemporary phase 3 trials); of those, 85% were assumed to receive maintenance. The model estimated median OS (mOS) among a maintenance-ineligible simulated cohort which when combined with the maintenance-eligible cohort yielded an estimated OS in the overall maintenance- intended population from 1L PBT initiation. Results: Approximately half of the modeled 1L PBT-treated population received maintenance. Estimated mOS was 10.1 months (95% CrI 7.5-13.5) for the maintenance-ineligible cohort, 29.3 months (95% CrI 24.8-33.9) for the maintenance-eligible, received maintenance cohort, and 15.9 months (95% CrI 13.2-19.1) in the overall maintenance-intended, 1L PBT-treated population, including those eligible and ineligible for maintenance. Conclusion: The model shows that maintenance avelumab has a modest impact on OS in the overall 1L PBT-treated population of patients with aUC. While maintenance avelumab improves OS for eligible patients, a large proportion of the maintenance-intended population may not receive maintenance due to ineligibility or physician/patient choice.

A randomized open-label trial with a crossover comparison of sexual self-confidence and other treatment outcomes following tadalafil once a day vs. tadalafil or sildenafil on-demand in men with erectile dysfunction.

AIM: To compare Sexual Self-Confidence and other treatment outcomes following 8 weeks of treatment with tadalafil 5 mg once a day (OaD) vs. tadalafil 20 mg or sildenafil 100 mg as needed (pro re nata [PRN]) in patients with erectile dysfunction (ED). METHODS: A randomized, open-label, crossover study in men ≥18 years of age with history of ED and satisfactory response to current oral phosphodiesterase 5 (PDE5) inhibitor PRN. Data were analyzed with a mixed effects model for crossover design. MAIN OUTCOME MEASURES: The primary outcome measure was the Sexual Self-Confidence domain of the Psychological and Interpersonal Relationship Scales (PAIRS) between tadalafil OaD and sildenafil PRN. SECONDARY OUTCOMES INCLUDED: Time Concerns and Spontaneity domains of PAIRS, and the Self-Esteem and Relationship (SEAR) scale. RESULTS: Men naive to tadalafil OaD were enrolled (N = 378), with 61-69% prior PDE5 inhibitor use. There were improvements in all PAIRS domains from baseline when comparing tadalafil OaD and PRN with sildenafil PRN (P < 0.001). The Sexual Self-Confidence domain improved from baseline and was 0.50 ± 0.78 following tadalafil OaD, 0.5 ± 0.72 for tadalafil PRN, and 0.39 ± 0.67 for sildenafil PRN. The difference in least-squares mean was 0.12 ± 0.04 (confidence interval [CI] = 0.04, 0.19; P = 0.001) between tadalafil OaD and sildenafil PRN and 0.01 ± 0.04 (CI = -0.06, 0.08; P = 0.872) between tadalafil OaD and tadalafil PRN. The Time Concerns domain score was lower with tadalafil OaD than tadalafil PRN (P < 0.001). There were no differences in SEAR scores between treatments. CONCLUSIONS: Tadalafil OaD and tadalafil PRN compared with sildenafil PRN demonstrated greater improvements in Sexual Self-Confidence, Time Concerns, and Spontaneity. There was no significant difference in Sexual Self-Confidence between tadalafil OaD and tadalafil PRN. Changes in SEAR, the erectile function domain of the International Index of Erectile Function, and the Erectile Dysfunction Inventory of Treatment Satisfaction scores from baseline to end point were similar.

Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: a geographical comparison from a single arm, open-label study.

INTRODUCTION: Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. AIM: To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). METHODS: Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of > or =6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. MAIN OUTCOMES MEASURES: Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. RESULTS: A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. CONCLUSION: Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use.

Efficacy and safety of tadalafil in the treatment of Latin American men with erectile dysfunction: results of integrated analyses.

INTRODUCTION: Available information on the efficacy and safety of tadalafil on Latin American men comes from reports where data is mixed with other populations. AIM: To assess the efficacy and safety of tadalafil in Latin American men with erectile dysfunction (ED). METHODS: Integrated analyses of data from four 12-week, randomized, double-blind, parallel, placebo-controlled trials conducted in Latin America that assessed the efficacy and safety of tadalafil in 406 Latin American men with ED of diverse etiology and severity assigned to placebo (N = 113), 10-mg tadalafil (N = 39), or 20-mg tadalafil (N = 254). MAIN OUTCOME MEASURES: Efficacy was assessed by International Index of Erectile Function Erectile Function (IIEF-EF) domain, questions 2 to 5 of the Sexual Encounter Profile and the first Global Assessment Question. Adverse events (AEs) reported by all enrolled patients were collected. RESULTS: Latin American patients treated with 10 or 20 mg of tadalafil had a significant mean improvement of 4.92 and 9.78, respectively, in the IIEF-EF domain score from baseline compared with 2.24 on placebo (P = 0.003 and P < 0.001, respectively, vs. placebo). At both doses, the mean success rate for penetration was 75 and 86%, respectively, compared with 56% on placebo (P < or = 0.001), the mean success rate for intercourse was 55% and 78%, compared with 36% on placebo (P < 0.001 vs. placebo), and 62% and 91% of patients, respectively, reported improved erections at the end point, vs. 43% on placebo (P = 0.160 and P < 0.001, respectively, vs. placebo). The most frequent AEs were headache, dyspepsia, and back pain. CONCLUSIONS: 10 or 20 mg tadalafil was an effective, safe, and well-tolerated therapy for Latin American men with ED of diverse etiology despite of ED severity.