Patient's adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: is combination therapy better than monotherapy?

BACKGROUND: Recent studies showed that the non-adherence to the pharmacological therapy of patients affected by BPH-associated LUTS increased the risk of clinical progression of BPH. We examined the patients adherence to pharmacological therapy and its clinical consequences in men with BPH-associated LUTS looking at the differences between drug classes comparing mono vs combination therapy. METHODS: A retrospective, population-based cohort study, using prescription administrative database and hospital discharge codes from a total of 1.5 million Italian men. Patients ≥ 40 years, administered alpha-blockers (AB) and 5alpha-reductase inhibitors (5ARIs), alone or in combination (CT), for BPH-associated LUTS were analyzed. The 1-year and long term adherence together with the analyses of hospitalization rates for BPH and BPH-related surgery were examined using multivariable Cox proportional hazards regression model and Pearson chi square test. RESULTS: Patients exposed to at least 6 months of therapy had a 1-year overall adherence of 29 % (monotherapy AB 35 %, monotherapy 5ARI 18 %, CT 9 %). Patient adherence progressively declined to 15 %, 8 % and 3 % for AB, 5ARI, and CT, respectively at the fifth year of follow up. Patients on CT had a higher discontinuation rate along all the follow-up compared to those under monotherapy with ABs or 5ARIs (all p < 0.0001). Moreover, CT was associated with a reduced risk of hospitalization for BPH-related surgery (HR 0.94; p < 0.0001) compared to AB monotherapy. CONCLUSIONS: Adherence to pharmacological therapy of BPH-associated LUTS is low and varies depending on drugs class. Patients under CT have a higher likelihood of discontinuing treatment for a number of reasons that should be better investigated. Our study suggests that new strategies aiming to increase patient's adherence to the prescribed treatment are necessary in order to prevent BPH progression.

The Current Indications and the Benefits of Combining a ß3-Agonist with an Anticholinergic for the Treatment of OAB.

UNLABELLED: Combination therapy with anti-muscarinics (AMs) and ß3 agonists (ß3As) has recently been proposed as a possible treatment for the management of patients with Overactive Bladder (OAB). EVIDENCE ACQUISITION: A National Center for Biotechnology Information PubMed search for relevant articles published between 2007 and 2014 was performed by combining the following Patient population, Intervention, Comparison, Outcome (PICO) terms: overactive bladder, antimuscarinics, ß3 agonists, combination therapy, efficacy, tolerability and outcomes. Additional references were obtained from the reference list of full-text manuscripts. Abstracts presented at the annual congresses of the European Association of Urology, American Urology Association and the International Continence Society were included. EVIDENCE SYNTHESIS: The combination therapy, in the management of OAB symptoms, has recently been investigated in animal models and in a phase II randomized clinical trial. Compared with AMs monotherapy, combination treatment improved mean voided volume per micturition, micturition frequency and reduced urgency episodes. No dose related trends in adverse events (AEs) were observed between combination group and monotherapy group. Incidence of constipation was slightly increased in combination therapy group. CONCLUSIONS: Combination therapy seems to be an effective and safe treatment in the management of OAB. However, further cost-effectiveness studies are needed to evaluate the definitive role of this approach for the management of patients with OAB.

Current Pharmacological Treatment for Male LUTS due to BPH: Dutasteride or Finasteride?

Benign prostatic hyperplasia (BPH) is a potentially progressive disease which is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. In the current medical therapy scenario for LUTS attributed to BPH, only one class of drugs, 5-α reductase inhibitors (5ARIs), has been found to be effective in reducing the risk of disease progression. The two 5ARIs that are currently available include finasteride and dutasteride. These two drugs have different pharmacokinetic and pharmacodynamic properties. Greater suppression of dehydrotestosterone is achieved by dutasteride (>90% dutasteride vs 70% finasteride) which theoretically should correlate with greater efficacy in alleviating urinary symptoms. Unfortunately, this hypothesis has not yet been clinically demonstrated. The pertinent literature is scarce and heterogeneous and produces low scientific levels of evidence. The present review article aims to evaluate the comparative head-to-head studies in order to evaluate if the hypothetical clinical differences between dutasteride and finasteride do exist. Pharmacological treatment with either drug results in similar symptom improvements; however dutasteride seems to have a better profile in reducing the risk of prostate surgery and acute urinary retention (AUR). More studies are necessary to better evaluate both the clinical and pharmacoeconomic profile of the two 5ARIs.

Drug adherence and clinical outcomes for patients under pharmacological therapy for lower urinary tract symptoms related to benign prostatic hyperplasia: population-based cohort study.

BACKGROUND: Little is known about drug adherence in men treated for lower urinary tract symptoms (LUTS). Benign prostatic hyperplasia (BPH) is one of the causes of LUTS. OBJECTIVE: To examine adherence to pharmacological therapy and its clinical value in men with LUTS. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study using an administrative prescription database and hospital discharge codes for 1.5 million men aged ≥40 yr treated with alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) alone or in combination (CT). INTERVENTIONS: Therapy with ABs and/or 5ARIs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The 1-yr and long-term adherence; hospitalization rates for BPH and BPH surgery. Multivariate Cox proportional hazards regression model, propensity score matching, and sensitivity analyses. RESULTS AND LIMITATIONS: The 1-yr adherence was 29% in patients exposed to at least 6-mo therapy. Patients on CT had a higher discontinuation rate in the first 2 yr compared to those on monotherapy (p<0.0001). Overall hospitalization rates for BPH and BPH surgery were 9.04 and 12.6 per 1000 patient-years, respectively. A lower risk of hospitalization was observed for 5ARI compared to AB therapy (hazard ratio [HR] 0.46 and 0.23; p<0.0001). CT was associated with a reduced risk of hospitalization for BPH surgery (HR 0.94; p<0.0001) compared to AB. Discontinuation of drug treatment was an independent risk factor for hospitalization for BPH and BPH surgery (HR 1.65 and 2.80; p<0.0001) regardless of therapeutic group. Limitations include the paucity of clinical measures and the absence of patient-reported outcomes. CONCLUSIONS: Adherence to pharmacological therapy for BPH is low and could affect clinical outcomes. Long-term 5ARI and CT use was associated with an independent reduced risk of hospitalization for BPH surgery. Our findings suggest the need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians. PATIENT SUMMARY: Our research shows that adherence to prescribed pharmacological therapy is crucial in the management of patients suffering from lower urinary tract symptoms. Moreover, pharmacological therapy can prevent disease progression.

Actual medical management of lower urinary tract symptoms related to benign prostatic hyperplasia: temporal trends of prescription and hospitalization rates over 5 years in a large population of Italian men.

PURPOSE: The purpose of the study is to estimate the trends in drug prescriptions and the hospitalization rates for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) in real-life clinical practice, using information deriving from administrative databases of the Italian health care system. METHODS: Prescription data on approximately 1,500,000 men over 40 were examined, and prescribed boxes of alpha-blockers (ABs) and/or 5 alpha reductase inhibitors (5ARI) were calculated for 5 consecutive years, from 2004 to 2008. Annual use prevalence and incidence rates for each drug class and for the combination therapy (CT) were calculated according to age for the entire study period. Hospitalization rates for reasons related to LUTS/BPH were also evaluated for the same time period. RESULTS: The overall distribution of drugs for LUTS/BPH, in terms of number of boxes prescribed, increased by 43 %. This increase was accounted for by both classes of drugs although it was greater for 5ARI than for AB (+49 vs +41 %). The prevalence of CT showed a substantial increase to almost 25 % in patients aged ≥75. Hospitalization rate for BPH/LUTS-related reasons decreased during the study period (8 and 3 % per year for non-surgical and surgical reasons, respectively). CONCLUSIONS: The prevalence of the use of drugs prescribed for LUTS/BPH has steadily increased. An increase in terms of prescribed boxes was observed for both classes of drugs, even though the increase was greater for 5ARIs. The reduction in the hospitalization rates needs additional researches.

The effects of dutasteride and finasteride on BPH-related hospitalization, surgery and prostate cancer diagnosis: a record-linkage analysis.

PURPOSE: To investigate differences in the risk of benign prostatic hyperplasia (BPH)-related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients using finasteride or dutasteride. METHODS: A retrospective cohort study was conducted using data from record linkage of administrative databases (pharmaceutical prescription data, hospital discharge records, Italian population registry). Men aged ≥ 40 years old who had received a prescription for at least 10 packs/year between January 1, 2004 and December 31, 2004 were included and followed for 5 years. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity score-matched analysis and a 5-1, greedy 1:1 matching algorithm were performed. RESULTS: 8,132 patients were identified. Overall incidence rates of BPH hospitalization and BPH-related surgery were 21.05 (95 % CI 19.52-22.71) and 20.97 (95 % CI 19.45-22.61) per 1,000 person-years, respectively. In the dutasteride group compared with finasteride group, the incidence rate of both events was statistically significant lower: 16.07 versus 21.76 for BPH hospitalization and 15.91 versus 21.69 for BPH-related surgery. The incidence rate of new PCa was also lower for the dutasteride group [8.34 (95 % CI 5.96-11.68) vs. 10.25 (95 % CI 9.15-11.49)]. Dutasteride was associated with a reduction in BPH-related hospitalizations (HR 0.75, 95 % CI 0.58-0.98 and 0.58-0.98 for surgical and non-surgical reasons). The matched analysis confirmed the risk reduction with dutasteride for BPH-related surgery. CONCLUSIONS: These findings suggest that the clinical effects of dutasteride and finasteride might be different. Patients treated with dutasteride seem to be less likely to experience BPH-related hospitalization. Comparative studies are needed to confirm these results.

Clinical effects and economical impact of dutasteride and finasteride therapy in Italian men with LUTS.

OBJECTIVES: To investigate differences in the risk of benign prostatic hyperplasia (BPH)- related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients under dutasteride or finasteride treatment. MATERIAL AND METHODS: A retrospective cohort study was conducted using data from record-linkage of administrative databases. Men aged ≥ 40 years old who had received a prescription for at least 10 boxes/year (index years: 2004-06) were included. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity score matched analysis and a 5-to-1, greedy 1:1 matching algorithm were performed. The budget impact analysis of dutasteride vs finasteride in BPH-treated patient was performed. RESULTS: From an initial cohort of about 1.5 million of Italian men, 19620 were selected. The overall hospitalization for BPH-non surgical reasons, for BPH-related surgery and for new detection of PCa incidence rates (IRs) were 8.20 (95% CI, 7.62-8.23), 18.0 (95% CI, 17.12-18.93) and 8.62 (95% CI, 8.03-9.26) per 1000 person-years, respectively. The multivariate analysis after the propensity score-matching showed that dutasteride was associated with an independent reduced likelihood of hospitalization for BPH-related surgery (HR 0.82; 95% CI 0.73-0.93; p = 0.0025) and of newly detected PCa (HR: 0.76,95% CI, 0.65-0.85; p = 0.0116). The IR for BPH-non surgical reasons was 8.07 (95% CI, 7.10-9.17) and 9.25 (95% CI, 8.19-10.44) per 1000 person-years, respectively. The IR for BPH-related surgery was 18.28 (95% CI, 17.17-20.32) and 21.28 (95% CI, 19.24-23.06) per 1000 person-years among patients under dutasteride compared with those under finasteride, respectively. For new-onset PCa, the IR was 8.01 (95% CI, 7.07-9.08) and 9.38 (95% CI, 8.32-10.58) per 1000 person-years The pharmacoeconomical evaluation showed that the net budget impact of the use of dutasteride vs. finasteride in 1000 BPH-treated patient for 1 year induces a saving of 3933 €. CONCLUSIONS: The clinical effects of dutasteride and finasteride are slightly different. The likelihood of hospitalization for BPH-related surgery and of newly detected PCa seems to be in favor of dutasteride. The budget impact analyses showed a slightly benefit for dutasteride. Comparative prospective studies are necessary to confirm these results.

[Memorandum for the management of clinical trials]. / Pro-memoria per la gestione della sperimentazione clinica.

A critical appraisal of the recent legislation on clinical trials is proposed, together with some reflections on the implications on the practice and principles of clinical experimentation. The possible role and contribution of Ethical Committees is discussed.