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.

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).

Drug utilization patterns and healthcare resource use and costs in patients with neurogenic bladder in the United Kingdom: A retrospective primary care database study.

AIM: To characterize patients with neurogenic bladder (NGB), their treatment patterns, healthcare resource utilization, and associated costs based on records from a primary care database in the United Kingdom. METHODS: This was a retrospective, descriptive, observational study of anonymized data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases (selection period, 1 January 2004 to 31 December 2016). Adults with a definitive or probable diagnosis of NGB and ≥1 referral to a urologist were included. RESULTS: The study cohort included 3913 patients with definitive (n = 363) or probable (n = 3550) NGB. Patients had a mean of 8.6 (standard deviation [SD], 7.6) comorbidities, and mean Anticholinergic Cognitive Burden Scale score of 6.6 (SD, 5.9). During 12 months' follow-up, urinary tract infection (UTI) and urinary incontinence were the most common complications. Most patients (92.2%) received ≥1 prescription for an antimuscarinic agent or mirabegron, and 53.9% of patients received prescriptions for UTI-specific antibiotics. The mean number of visits to a general practitioner for any cause was 67.7 (SD, 42.6) per individual. Almost half (46.7%) of the study cohort visited a specialist during the 12-month follow-up period, and 11.0% had ≥1 hospital admission. Total mean per patient costs for healthcare resource utilization was £2395. CONCLUSIONS: The burden of illness, healthcare resource needs, and associated costs among patients with NGB are considerable. Drug prescribing patterns are consistent with the symptoms and complications of NGB, although increased awareness of drugs with anticholinergic activity among prescribers may help to reduce the cumulative anticholinergic burden in this vulnerable population.

A critical appraisal of the principal guidelines for neurogenic lower urinary tract dysfunction using the AGREE II instrument.

AIMS: The process of identifying research questions, synthesizing and interpreting evidence, and weight given to health economics differs between the clinical guidelines (CGs) for neurogenic lower urinary tract dysfunction (NLUTD). Consequently, the quality also varies which can have implications for clinical practice. METHODS: We used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to assess the quality of the National Institute for Health and Care Excellent (NICE), European Association of Urology (EAU), and the International Consultations on Incontinence (ICI) CGs on neurogenic bladder. RESULTS: The NICE CGs were deemed to be of the highest quality (overall score of 92%). NICE were the only guidelines to systematically incorporate cost-effectiveness research into their recommendations. The EAU CGs received an overall score of 83% and the ICI CGs achieved the lowest overall score (75%). The highest scoring domain among all the CGs was scope purpose (86%) and the lowest scoring domain was applicability (69%). All guidelines were recommended for use (mostly with some modifications). CONCLUSIONS: All CGs had their inherent advantages and disadvantages, though all were still deemed to be of high quality. Incorporating cost-effectiveness research would be near impossible for guidelines with a broad-country remit. Incorporating the AGREE II instrument in the development of CGs and better collaboration between the ICI, NICE, and EAU could improve the quality, and consistency between NLUTD CGs and ultimately improve health outcomes for this important patient group.

A comparison of the treatment recommendations for neurogenic lower urinary tract dysfunction in the national institute for health and care excellence, European Association of Urology and international consultations on incontinence guidelines.

AIMS: Healthcare guidelines are an important vehicle in establishing up-to-date evidence based medicine (EBM) in clinical practice. Due to varying development processes, clinical guidelines created by different institutions can often contain contrasting recommendations. This can have implications for optimal and standardized patient care across management settings. METHODS: The similarities and differences of treatment recommendations made in the National Institute for Health and Care Excellence (NICE), The European Association of Urology (EAU), and the International Consultation on Continence (ICI) guidelines for neurogenic lower urinary tract dysfunction (NLUTD) were assessed. RESULTS: The guidelines generally agree on their approach to conservative management, including behavioral therapies, and catheterization techniques. There was discrepancy on the benefit of using an alpha blocker in NLUTD and bladder outlet obstruction (BOO) and administering Botulinum toxin A (Onabotulinum-A) in NLUTD. The highest degree of divergence was seen in recommendations for surgical treatments, where the EAU made gender-specific recommendations, and gave continent urinary diversion higher preference than given in the NICE and ICI guidelines. CONCLUSIONS: In the absence of high-quality clinical evidence, many of the recommendations made across all three guidelines are based on expert opinion. NICE, the EAU and ICI have similarities but they place differing emphasis on costs and expert opinion, which translated in notably different recommendations. It is evident that increased research efforts, possibly in the form of prospective registries, pragmatic trials, and resource utilization studies are necessary to improve the underlying evidence base for NLUTD, and subsequently the strength and concordance of recommendations across guidelines.

Real world treatment patterns in the neurogenic bladder population: a systematic literature review.

Myriad treatment modalities are available for neurogenic bladder (NGB) including behavioral therapies, oral pharmacotherapy, catheterization and surgical procedures. Little is known about how NGB patients are managed in the real world, how well patterns relate to clinical guidelines and how strategies may have changed over time. To address this gap, a systematic review (SR) was conducted using MEDLINE and EMBASE [1996-2017]. The inclusion criteria for studies were: (I) published in English; (II) conducted in human subjects; (III) reporting the treatment patterns/use in NGB; (IV) conducted in a real world setting. A narrative synthesis of results was conducted, comparing the results to current treatment guidelines. Percentage of treatment use was summarized using ranges. Eight studies met the inclusion criteria. Although most studies focused on spinal cord injuries (SCI), study designs and settings were heterogeneous. All data was collected before 2007. The most popular form of oral pharmacotherapy was antimuscarinics, used by 12.6-86.7% of patients; 0-100% of patients used catheterization techniques, 2.5-53.1% used reflex voiding (RV), and 0.2-55% underwent surgery. A notable amount of patients switched treatments. This SR revealed that numerous strategies have been used to manage NGB throughout the years and there has been a large variance in their use. Whilst there were some discrepancies, most practices matched recommendations made in current guidelines. Ultimately, this SR showed that there is a large gap of epidemiological studies conducted in the field of NGB and the authors felt that available data was insufficient to build a comprehensive picture of treatment patterns. Epidemiological studies using electronic medical records (EMRs) are necessary to advance our understanding of how treatment patterns have changed, and also build a comprehensive picture of how patients are managed in current practice.