The use of mono- and combination drug therapy in men and women with lower urinary tract symptoms (LUTS) in the UK: a retrospective observational study.

BACKGROUND: Combination drug therapy for lower urinary tract symptoms (LUTS) is beneficial to selected patients and recommended by guidelines. Patterns of real-world LUTS drug use, especially combination drug therapy, have not been studied extensively. Moreover, further understanding of the recent landscape is required following the introduction of the beta-3-adrenoceptor agonist mirabegron in the UK in 2013 for overactive bladder (OAB). The objective was to describe mono- and combination drug therapy use for LUTS in patients in UK clinical practice. METHODS: This was a retrospective, descriptive, observational database study using UK Clinical Practice Research Datalink GOLD and linked databases. Men and women ≥ 18 years with a first prescription for any LUTS drug from 2014 to 2016 with ≥ 12 months continuous enrollment pre- and post-index date were included. Primary endpoints were mono- or combination drug therapy use for LUTS in male and female cohorts. Secondary endpoints were description of treatment prescribed, treatment persistence and patient demographics. Data were analyzed descriptively. Sub-cohorts were defined by drugs prescribed at index date. RESULTS: 79,472 patients (61.3% male) were included, based on index treatments. Of all men, 82.5% received any benign prostatic obstruction (BPO) drug, 25.4% any OAB drug, and 7.9% any BPO drug plus any OAB drug. As either mono- or combination drug therapy, 77.1% received an alpha-blocker, 18.9% a 5-alpha reductase inhibitor, 23.9% an antimuscarinic agent, and 2.1% mirabegron. Of all women, 94.5% received any OAB drug, 6.0% duloxetine, and 0.5% any OAB drug plus duloxetine. As either mono- or combination drug therapy, 87.7% received an antimuscarinic, and 9.7% mirabegron. In men or women receiving OAB treatment, approximately 2.5% received combination drug therapy with an antimuscarinic agent and mirabegron. For OAB drug monotherapies, mirabegron had the highest persistence in both male and female cohorts. CONCLUSIONS: This study provides a better understanding of the recent landscape of LUTS drug use in UK clinical practice. It highlights potential undertreatment of storage symptoms in men with LUTS and the low use of combination OAB treatments.

Anticholinergic Burden and Associated Healthcare Resource Utilization in Older Adults with Overactive Bladder.

BACKGROUND: Bladder anticholinergics are the most widely used drugs to treat overactive bladder (OAB) but can contribute to cumulative anticholinergic burden, which may be associated with adverse outcomes. OBJECTIVE: This study aimed to evaluate the association between cumulative anticholinergic burden and healthcare resource utilization (HRU) and costs in older adults with OAB. MATERIALS AND METHODS: This was a retrospective, observational study that used data from the UK Clinical Practice Research Datalink (CPRD) GOLD database. Participants were aged ≥ 65 years with ≥ 3 years of continuous enrolment before and ≥ 2 years after the index date (date of OAB diagnosis or first prescription for any OAB drug between 1 April 2007 and 31 December 2015). The primary endpoint was the association between cumulative anticholinergic burden (assessed using the Anticholinergic Cognitive Burden [ACB] scale during the 3-year pre-index period) and HRU (GP consultations, specialist referrals, urological tests, hospital admissions) over the 2-year post-index period. RESULTS: Data from 23,561 adults were included in the analysis. Mean (SD) ACB scores in the pre- and post-index periods were 1.0 (1.1) and 2.4 (1.7), respectively; urological drugs contributed most (58.8%) to the latter. For the primary endpoint, higher pre-index ACB scores were associated with higher post-index HRU and costs. Mean (SD) ACB scores in the post-index period were 1.2 (1.3) and 2.5 (1.7) in those treated with mirabegron (beta-3 agonist) or bladder anticholinergics, respectively. LIMITATIONS: The generalizability of the results outside the UK is unclear. CONCLUSIONS: In older adults with OAB, higher anticholinergic burden before initiating OAB drugs is associated with higher HRU and costs. When making treatment decisions in older adults, consideration should be given to assessing the existing anticholinergic burden and using OAB treatments that do not add to this burden.

Análisis de costes y consecuencias relacionados con la persistencia del tratamiento con Mirabegrón y los fármacos antimuscarínicos y su impacto sobre la calidad de vida en los pacientes con vejiga hiperactiva en España: resultados de un modelo probabilístico / Analysis of costs and consequences related to the persistence of Mirabegron and antimuscarinic treatments and their impact on quality of life in patients with overactive bladder in Spain: Results of a probabilistic model

OBJETIVO: Evaluar si la menor tasa de abandonos del tratamiento de la vejiga hiperactiva (VH) con mirabegrón podría generar ahorros para el Sistema Nacional de Salud (SNS) y ganancia de años de vida ajustados por calidad (AVACs), en comparación con los fármacos antimuscarínicos (AM) (tolterodina, fesoterodina, oxibutinina, solifenacina). MÉTODOS: Modelo probabilístico (simulación de Monte Carlo de segundo orden) en una cohorte hipotética de 1.000 pacientes con VH y un horizonte temporal de 1 año. Las tasas de abandono/persistencia del tratamiento con mirabegrón y AM se obtuvieron de un estudio observacional español en 1.798 pacientes. Los costes unitarios (€ 2018) y la pérdida de utilidades ligada al abandono del tratamiento se obtuvieron de precios públicos españoles y de la literatura, respectivamente. RESULTADOS: En cada paciente tratado con mirabegrón se duplica la tasa de persistencia en comparación con los AM, ganándose anualmente 0,0151 ±0,0007 AVACs, frente a AM. Con mirabegrón se generaría un ahorro anual por paciente de 80,74 ± 4,61 € en comparación con los AM, con una probabilidad de ahorro del 100%. La sustitución hipotética de los AM por mirabegrón, generaría en el plazo de 1 año un ahorro para el SNS de 6,6 millones de euros (IC 95%3,9-10,1 millones de euros) y se ganarían 1.238 AVAC (IC95% 731; 1.885 AVAC). CONCLUSIONES: El modelo probabilístico muestra una mayor persistencia en pacientes tratados con mirabegrón en comparación con los AM, generando un impacto positivo sobre la calidad de vida de los pacientes así como ahorros para el SNS

OBJECTIVE: To evaluate whether the lower dropout rate of the treatment of overactive bladder (OAB) with mirabegron could generate cost savings to the National Health System (NHS) and lead to quality-adjusted life years (QALYs) gains, compared to the most commonly prescribed antimuscarinics (AM) in Spain (tolterodine, fesoterodine, oxybutynin, solifenacin). METHODS: A probabilistic model (second order Monte Carlo simulation) in a hypothetical cohort of 1,000 patients with OAB and a time horizon of 1 year was carried out. Discontinuation and persistence rates for both mirabegron and AM were obtained from a Spanish observational study in 1798 patients. Unit costs (€ 2018) and utility loss associated with treatment discontinuation were obtained from Spanish public prices and literature, respectively. RESULTS: Persistence rates in patients treated with mirabegron were twice as high compared to AM, leading to a QALY gain of 0.0151 ± 0.0007 per year. Treatment with mirabegron could generate savings of 80.74 ± 4.61 € per patient per year compared to AM, assuming 100% probability of saving. The hypothetical substitution of AM treatment for mirabegron could potentially generate savings of 6.6 million euros (95% CI 3.9-10.1 million euros) to the NHS and 1,238 QALYs gains (CI 95% 731; 1,885 QALYs) within a period of 1 year. CONCLUSIONS: The probabilistic model presented showed a greater persistence in patients treated with mirabegron compared to AM, leading to a positive impact in patients quality of life, as well cost savings to the NHS in Spain

A retrospective analysis comparing persistence and adherence to treatment with free- vs fixed-dose combination of an alpha blocker and an antimuscarinic agent in men with LUTS in Spain.

INTRODUCTION: Combination therapy with an alpha blocker (AB) plus an antimuscarinic (AM) is recommended for men with moderate-to-severe mixed lower urinary tract symptoms (LUTS) when monotherapy is not effective in relieving storage symptoms. This study compared treatment persistence and adherence with an AB plus AM fixed-dose combination (FDC) vs an AB plus AM free-dose combination in men with LUTS in Spain. METHODS: Retrospective study using the Spanish IQVIA Cegedim Electronic Medical Records database. Men prescribed AB plus AM combination therapy were included in an FDC or free-dose combination cohort based on their index treatment. Treatment persistence was the time from index date to first discontinuation of ≥1 of the two index drugs over 12 months. Adherence was measured using the fixed medication possession ratio (MPR). RESULTS: Of 3114 patients identified, 999 were included (FDC, n = 790; free-dose combination, n = 209). Median (95% CI) persistence was longer in the FDC (125 [109-151] days) than in the free-dose combination (31 [31-36] days) cohort (hazard ratio [HR], 2.9; 95% CI, 2.4-3.4; P < .0001). The 12-month persistence rates were 31.1% (FDC cohort) and 8.9% (free-dose cohort). The mean (SD) fixed MPR was higher in the FDC cohort (48.8 [37.2]) compared with the free-dose cohort (23.1 [28.4]); more patients in the FDC cohort (34.2%) than in the free-dose cohort (10.0%) were adherent (MPR ≥ 80%). The probability of treatment persistence and adherence increased with age (>80 vs <65 years, persistence HR, 0.7 [95% CI, 0.5-0.9]; MPR difference, 12.5), polypharmacy (persistence HR, 0.7 [95% CI, 0.6-0.9]; MPR difference, 10.7) and previous use of AB (persistence HR, 0.8 [95% CI, 0.7-1.0]; MPR difference, 5.7) or AB/AM combinations (persistence HR, 0.7 [95% CI, 0.5-0.9]; MPR difference, 11.1). CONCLUSIONS: Treatment with an AB/AM FDC is associated with better persistence and adherence vs a free-dose combination in men with LUTS in Spain.

[Analysis of costs and consequences related to the persistence of Mirabegron and antimuscarinic treatments and their impact on quality of life in patients with overactive bladder in Spain: Results of a probabilistic model.] / Análisis de costes y consecuencias relacionados con la persistencia del tratamiento con Mirabegrón y los fármacos antimuscarínicos y su impacto sobre la calidad de vida en los pacientes con vejiga hiperactiva en España: resultados de un modelo probabilístico.

OBJECTIVE: To evaluate whether the lower dropout rate of the treatment of overactive bladde r(OAB) with mirabegron could generate cost savings to the National Health System (NHS) and lead to quality-adjusted life years (QALYs) gains, compared to the most commonly prescribed antimuscarinics (AM) in Spain (tolterodine, fesoterodine, oxybutynin, solifenacin). METHODS: A probabilistic model (second order Monte Carlo simulation) in a hypothetical cohort of 1,000 patients with OAB and a time horizon of 1 year was carried out. Discontinuation and persistence rates for both mirabegron and AM were obtained from a Spanish observational study in 1798 patients. Unit costs (€ 2018) and utility loss associated with treatment discontinuation were obtained from Spanish public prices and literature, respectively. RESULTS: Persistence rates in patients treated with mirabegron were twice as high compared to AM, leading to a QALY gain of 0.0151 ± 0.0007 per year. Treatment with mirabegron could generate savings of 80.74 ±4.61 € per patient per year compared to AM, assuming 100% probability of saving. The hypothetical substitution of AM treatment for mirabegron could potentially generate savings of 6.6 million euros (95% CI 3.9-10.1 million euros) to the NHS and 1,238 QALYs gains (CI95%731; 1,885 QALYs) within a period of 1 year. CONCLUSIONS: The probabilistic model presented showed a greater persistence in patients treated with mirabegron compared to AM, leading to a positive impactin patients quality of life, as well cost savings to the NHS in Spain.

OBJETIVO: Evaluar si la menor tasa de abandonos del tratamiento de la vejiga hiperactiva (VH) con mirabegrón podría generar ahorros para el Sistema Nacional de Salud (SNS) y ganancia de años de vida ajustados por calidad (AVACs), en comparación con los fármacos antimuscarínicos (AM) (tolterodina, fesoterodina, oxibutinina, solifenacina).MÉTODOS: Modelo probabilístico (simulación de Monte Carlo de segundo orden) en una cohorte hipotética de 1.000 pacientes con VH y un horizonte temporal  de 1 año. Las tasas de abandono/persistencia del tratamiento con mirabegrón y AM se obtuvieron de un estudio observacional español en 1.798 pacientes. Los costes unitarios (€ 2018) y la pérdida de utilidades ligada al abandono del tratamiento se obtuvieron de precios públicos españoles y de la literatura, respectivamente. RESULTADOS: En cada paciente tratado con mirabegrón se duplica la tasa de persistencia en comparación con los AM, ganándose anualmente 0,0151 ±0,0007 AVACs, frente a AM. Con mirabegrón se generaría un ahorro anual por paciente de 80,74 ± 4,61 € en comparación con los AM, con una probabilidad de ahorro del 100%. La sustitución hipotética de los AM por mirabegrón, generaría en el plazo de 1 año un ahorro para el SNS de 6,6 millones de euros (IC 95%3,9-10,1 millones de euros) y se ganarían 1.238 AVAC (IC95% 731; 1.885 AVAC). CONCLUSIONES: El modelo probabilístico muestra una mayor persistencia en pacientes tratados con mirabegrón en comparación con los AM, generando un impacto positivo sobre la calidad de vida de los pacientes así como ahorros para el SNS.

The real world impact of adalimumab on quality of life and the physical and psychological effects of moderate-to-severe psoriasis: a UK prospective, multicenter, observational study.

Psoriasis can adversely affect quality of life (QoL) and emotional well-being. In this UK prospective observational study we evaluated the 'real-world' impact of adalimumab on QoL and the physical/psychological effects of moderate-to-severe psoriasis. Hundred and forty-three biologic-naïve patients with moderate-to-severe psoriasis, receiving adalimumab in clinical practice, were included. Patients completed a series of questionnaires at baseline (adalimumab initiation), 4 and 16-weeks and 6-months post-adalimumab initiation during routine visits. The main outcome measure was the proportion of Dermatology Life Quality Index (DLQI) 'responders' at 16 weeks, defined as ≥5 point reduction from baseline or DLQI = 0.90% (95% CI = 80.8%-94.6%) of evaluable patients were DLQI responders at 16-weeks. There were significant improvements at 16 weeks in patient-reported measures of QoL, mental and physical well-being, cutaneous body image, anxiety, depression and psoriasis severity, which were maintained at 6-months. Adalimumab treatment was associated with improvements in patients' QoL and psychological functioning, which occurred contemporaneously with improvements in cutaneous disease.

Qualitative Analysis of Factors Influencing Patient Persistence and Adherence to Prescribed Overactive Bladder Medication in UK Primary Care.

INTRODUCTION: Pharmacotherapy for overactive bladder (OAB) is generally associated with low rates of persistence and adherence. This study was conducted to explore the patient journey in a UK primary care setting (experiences, perceptions, attitudes, and levels of engagement and expectations) and identify self-reported reasons for patient non-adherence and/or non-persistence to medications for OAB. METHODS: This was a qualitative, non-interventional study involving one-to-one semi-structured, face-to-face or phone interviews with individuals aged 40-80 years, diagnosed with OAB, and currently taking, or having taken, either antimuscarinic or ß3-adrenoceptor agonist medications within the last 12 months. Thematic analyses of interview transcripts identified themes surrounding the participants' experiences with OAB. RESULTS: A total of 20 interviews were conducted (face-to-face, n = 13; telephone, n = 7). Interviews from five men and 13 women (mean age 70 years) were included in the final analysis. The most common OAB symptoms reported included urgency, frequency, incontinence and nocturia. Several key themes of factors influencing persistence and/or adherence to prescribed OAB medication were identified: patients' attitude and condition adaptation behaviour; support with treatment; unmet efficacy/tolerability expectations; drug/condition hierarchy. Non-adherence and/or non-persistence to OAB medication was largely intentional, with patients balancing side effects against perceived clinical benefits. Perceived lack of efficacy was the primary reason for discontinuing treatment. Other factors cited included side effects of medication (either experienced or a fear of future effects), a general aversion to long-term medication taking, drug/condition hierarchy relative to other comorbidities, and limited healthcare professional (HCP) support/engagement. Patients expressed condition adaptation behaviours to help self-manage their condition. CONCLUSION: Persistence and adherence to OAB medication may be suboptimal. HCPs might be able to improve persistence and adherence by fostering realistic treatment expectations and scheduling regular medication reviews. These measures may help optimise patient care and support more adherent behaviours, thus minimising the impact of undertreated OAB on patient quality of life. FUNDING: Innovate UK and Astellas Pharma Europe Ltd (APEL).

The Last Year Before Graft Failure Negatively Impacts Economic Outcomes and is Associated With Greater Healthcare Resource Utilization Compared With Previous Years in the United Kingdom: Results of a Retrospective Observational Study.

BACKGROUND: Kidney and liver transplantation is the standard of care for end-stage renal or liver disease. However, long-term survival of kidney and liver grafts remain suboptimal. Our study aimed to understand the healthcare resources utilized and their associated costs in the years before graft failure. METHODS: Two noninterventional, retrospective, observational studies were conducted in cohorts of kidney or liver transplant patients. Once identified, patients were followed using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics databases from the date of transplantation to the date of the first graft failure. Total healthcare costs in the year before graft failure (primary endpoint) and during years 2-5 before graft failure (secondary endpoint) were collected. RESULTS: A total of 269 kidney and 81 liver transplant patients were analyzed. The mean total costs were highest for all resource components in the last year before graft failure, except for mean costs of immunosuppressive therapy per patient, which decreased slightly by index date (ie, graft failure). The mean total healthcare costs in the last year before graft failure were £8115 for kidney and £9988 for liver transplant patients and were significantly (P < 0.05) higher than years 2-5 before graft failure. Mean healthcare costs for years 2, 3, 4, and 5 before graft failure were £5925, £5575, £5469, and £5468, respectively, for kidney, and £6763, £7042, £6020, and £5651, respectively, for liver transplant patients. CONCLUSIONS: Total healthcare costs in the last year before graft failure are substantial and statistically significantly higher than years 2-5 before graft failure, in both kidney and liver transplant patients. Our findings show the economic burden placed on healthcare services in the years before graft failure.