Drug Therapy For Overactive Bladder Research Articles

Personalized approach to pharmacotherapy of overactive bladder

The article provides an overview of modern approaches to pharmacotherapy of overactive bladder. It has been shown that the choice of drug therapy for overactive bladder should be made taking into account the pathophysiological mechanisms of the development of the disease, the characteristics of its clinical course, as well as the potential risks of developing side effects of treatment. A pathogenetic rationale for the choice of treatment tactics for different categories of patients is presented, including those with a hypersensitive bladder, bladder outlet obstruction, neurological and geriatric patients. The pharmacological properties of the β3-adrenergic receptor agonist mirabegron are described, which provide high efficacy and a favorable safety profile in the treatment of patients with overactive bladder. The practical issues of prescribing mirabegron in various clinical situations are considered.

Persistence with mirabegron or antimuscarinic treatment for overactive bladder syndrome: Findings from the PERSPECTIVE registry study.

ObjectivesThis analysis from the PERSPECTIVE (a Prospective, Non‐interventional Registry Study of Patients Initiating a Course of Drug Therapy for Overactive Bladder) study evaluated treatment persistence with mirabegron or antimuscarinics over a 12‐month period.MethodsParticipants were adults diagnosed with overactive bladder (OAB) by their health care provider (HCP), who were initiating mirabegron or antimuscarinic treatment. The HCP made all treatment decisions, and patients were followed for 12 months with no mandatory scheduled visits. Information requests were sent to patients at baseline and months 1, 3, 6, and 12. Patients were nonpersistent if they switched, discontinued, or added OAB medications/therapies to their initial treatment. Reasons for discontinuation and switching patterns were investigated.ResultsOverall, 1514 patients were included (613 mirabegron and 901 antimuscarinic initiators). Persistence rates decreased steadily over time in both groups. A low proportion of patients added or switched medication at each time point. Unadjusted Kaplan‐Meier analysis showed similar persistence rates for both groups. When the data were adjusted for patient characteristics (age, sex, and OAB treatment status), mirabegron initiators had higher persistence rates. No significant differences were noted in unadjusted median time to end of persistence. However, end of treatment persistence by any cause was longer with mirabegron (median: 9.5 vs 6.7 months for antimuscarinics). HCPs stated that the most common reasons for nonpersistence were no symptomatic improvement and side effect aversion.ConclusionsTreatment persistence was longer for mirabegron compared with antimuscarinic initiators after controlling for patient characteristics. End of treatment persistence by any cause was also longer with mirabegron.

Effectiveness of Combined Behavioral and Drug Therapy for Overactive Bladder Symptoms in Men

First-line behavioral and drug therapies for overactive bladder (OAB) symptoms in men are effective but not usually curative. To determine whether combining behavioral and drug therapies improves outcomes compared with each therapy alone for OAB in men and to compare 3 sequences for implementing combined therapy. In this 3-site, 2-stage, 3-arm randomized clinical trial, participants were randomized to 6 weeks of behavioral therapy alone, drug therapy alone, or combined therapy followed by step-up to 6 weeks of combined therapy for all groups. Participants were recruited from 3 outpatient clinics and included community-dwelling men 40 years or older with urinary urgency and 9 or more voids per 24 hours. Data were collected from July 2010 to July 2015 and analyzed from April 2016 to September 2019. Behavioral therapy consisted of pelvic floor muscle training with urge suppression strategies and delayed voiding. Drug therapy included an antimuscarinic (sustained-release tolterodine, 4 mg) plus an α-blocker (tamsulosin, 0.4 mg). Seven-day bladder diaries completed before and after each 6-week treatment stage were used to calculate reduction in frequency of urination (primary outcome) and other symptoms (ie, urgency, urgency incontinence, and nocturia). Other secondary outcomes included validated patient global ratings of improvement and satisfaction, Overactive Bladder Questionnaire score, and International Prostate Symptom Score. Of the 204 included men, 133 (65.2%) were white, and the mean (SD) age was 64.1 (11.1) years. A total of 21 men discontinued treatment and 183 completed treatment. Mean (SD) voids per 24 hours decreased significantly in all 3 groups from baseline to 6-week follow-up (behavioral therapy: 11.7 [2.4] vs 8.8 [2.1]; change, 2.9 [2.4]; percentage change, 24.7%; P < .001; drug therapy: 11.8 [2.5] vs 10.3 [2.7]; change, 1.5 [2.3]; percentage change, 12.7%; P < .001; combined therapy: 11.8 [2.4] vs 8.2 [2.3]; change, 3.6 [2.1]; percentage change, 30.5%; P < .001). Intention-to-treat analyses indicated that posttreatment mean (SD) voiding frequencies were significantly lower in those receiving combined therapy compared with drug therapy alone (8.2 [2.3] vs 10.3 [2.7]; P < .001) but not significantly lower compared with those receiving behavioral therapy alone (8.2 [2.3] vs 8.8 [2.1]; P = .19) and were lower for behavioral therapy alone compared with drug therapy alone (8.8 [2.1] vs 10.3 [2.7]; P < .001). At 12-week follow-up, after all groups had received combined therapy, improvements in mean (SD) voids per 24 hours were also greatest for those receiving initial combined therapy compared with baseline (behavioral therapy: 11.7 [2.4] vs 8.0 [2.2]; change, 3.7 [2.3]; percentage change, 31.6%; P < .001; drug therapy: 11.8 [2.5] vs 8.6 [2.3]; change, 3.2 [2.5]; percentage change, 27.1%; P < .001; combined therapy: 11.8 [2.4] vs 8.0 [2.2]; change, 3.8 [2.1]; percentage change, 32.2%; P < .001), but there were no statistically significant group differences on primary or secondary measures. Combining behavioral and drug therapy yields greater improvements in OAB symptoms than drug therapy alone but not behavioral therapy alone. When using a stepped approach, it is reasonable to begin with behavioral therapy alone. ClinicalTrials.gov identifier: NCT01175382.

Factors Associated with Improvements in Patient-Reported Outcomes During Mirabegron or Antimuscarinic Treatment of Overactive Bladder Syndrome: A Registry Study (PERSPECTIVE).

IntroductionPatient-reported outcomes (PROs) provide valuable insights about the effectiveness of overactive bladder (OAB) treatments. The aim of PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder) was to provide real-world evidence from the USA and Canada on patient-perceived effectiveness and safety of mirabegron and antimuscarinics for treating OAB symptoms.MethodsThis prospective, non-interventional registry followed adult patients with OAB who were starting treatment with mirabegron or antimuscarinics. All treatment decisions were made at the discretion of the treating healthcare provider with no mandatory visits after enrollment. The primary objective was to identify factors associated with improved treatment effectiveness from a patient perspective mainly using the OAB Questionnaire Short-Form (OAB-q SF). The form was sent to patients via email link at baseline and months 1, 3, 6, and 12. Treatment-emergent adverse event (TEAE) data were collated from investigator reports.ResultsOverall, 1514 patients were included (female 73.5%, mean age 62.2 years). Mirabegron was initiated by 613 patients and antimuscarinics by 901 patients. A PRO response rate of approximately 60% was achieved (575 patients did not complete baseline PROs). Similar improvements in OAB-q SF symptom bother score and health-related quality of life (HRQoL) total score were observed for mirabegron and antimuscarinic initiators. Covariate-adjusted models demonstrated that worse baseline PRO score, Hispanic ethnicity, being treatment naïve, and use of complementary/supportive OAB therapies at baseline were significantly associated with greater improvements in both scores. The most frequent TEAEs were gastrointestinal disorders (dry mouth, constipation, and nausea) and nervous system disorders (headache, somnolence, and dizziness).ConclusionThere are no differences between mirabegron and antimuscarinics in terms of patient-reported OAB symptom bother and HRQoL.Trial RegistrationClinicalTrials.gov identifier, NCT02386072.FundingAstellas Pharma Global Development, Inc.Plain Language SummaryPlain language summary available for this article.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-019-00994-7) contains supplementary material, which is available to authorized users.

Choosing oral drug therapy for overactive bladder in older people

ABSTRACTIntroduction: Overactive bladder (OAB) and urgency incontinence are common in older people. Nevertheless, there remains a paucity of prospectively collected data on the efficacy of commonly used drug treatments for the condition. Many trials have included older people, but have seldom reported results stratified by age or reported adverse events of particular relevance to older people in clinical practice. This has partially been rectified with the introduction of more recently introduced antimuscarinic agents, particularly fesoterodine, and the beta-3-agonist, mirabegron.Areas covered: This article discusses evidence from recent trials relevant to robust and medically complex older people including synthesis of evidence on the association of anticholinergic medications and impaired cognition with relevance to OAB medicationsExpert opinion: There are increasing data concerning pharmacological therapy in both robust and medically complex older adults. There is a need to explore the efficacy and tolerability of pharmacological treatment of OAB and UUI (urgency urinary incontinence) in specific subgroups and to produce confirmatory real-world data on efficacy and tolerability. Guidelines which address treatment of older people is currently sparse but, as time progresses and data improve, more specific guidance should become available.

A Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder (PERSPECTIVE): Rationale, design, and methodology

IntroductionPharmacotherapy of overactive bladder (OAB) typically involves treatment with an antimuscarinic or mirabegron, a β3-adrenoceptor agonist, but real-world evidence on their use, including treatment access, persistence, and switching, is limited. Here, we describe the design of a prospective, multicenter, non-interventional registry of patients beginning a new course of OAB pharmacological therapy in routine clinical practice. MethodsAdults with an OAB diagnosis for at least 3 months who either initiated a new course of mirabegron or antimuscarinic, or who switched therapy were enrolled into PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder). The primary objective was to identify factors associated with improved OAB treatment effectiveness from a patient perspective. Secondary objectives were to compare persistence rates, reasons for discontinuation, and switching patterns between patients taking mirabegron or antimuscarinics. Healthcare centers and sites involving medical specialties who routinely participate in the care and treatment of patients with OAB (e.g., gynecology, urology, and primary care practices) were targeted for recruitment. Patient-reported outcomes (PROs), including quality of life, symptom bother, and treatment satisfaction from OAB-validated scales, were collected at baseline, months 1, 3, 6, and 12, and when patients switched or discontinued their current OAB medication. ConclusionsPERSPECTIVE is the first real-world observational study in the United States and Canada on clinical and patient perspectives in OAB management. Recruitment was reflective of centers where patients are treated for OAB to maximize generalizability to the real-world population.Trial registration: ClinicalTrials.gov, ID number NCT02386072 (date of registration March 6, 2015).

Prevalence and predictors of overactive bladder in nonpregnant nulliparous women below 65years of age.

The aetiology of the overactive bladder (OAB) symptom complex is still poorly understood. In order to obtain further insight, the prevalence and predictors of the symptoms included in OAB, that is urgency, urgency incontinence (UUI), frequency and nocturia, were investigated in a sample of nonpregnant nulliparous women. A national, postal and web-based survey of OAB symptoms was conducted in women aged 25-64years (n=9,197). Crude prevalence and prevalence adjusted according to body mass index (BMI) were calculated from a logistic regression model to evaluate the prevalence of OAB. The response rate was 52%. The prevalence of urgency, bothersome urgency, UUI, and nocturia, but not daytime frequency, increased consistently with advancing age and increasing BMI. Urgency was associated with BMI, age ≥45years, nocturia, and daytime frequency of eight or more micturitions. Daytime urinary micturition frequency was not affected by age either in women with OAB or in women without OAB. Bothersome OAB affected almost half of the woman in the oldest age group and was strongly associated with nocturia of two or more micturitions and OAB with UUI. There were contrasting changes in the prevalence of the different symptoms included in OAB. With increasing age and BMI, the prevalence of nocturia, urgency and UUI increased, while daytime frequency remained stable. These findings are of importance as the primary endpoint for the evaluation of drug therapies for OAB has often been daytime urinary frequency.

Current evidence and emerging drug therapies for overactive bladder.

Overactive bladder is a common symptom complex with health related quality of life impacts on the individual as well as utilizing health resources. Antimuscarinic therapy has been the mainstay of treatment and is well supported within the literature and guidelines. However, compliance is poor due to lack of efficacy and adverse events leading to the development of novel therapies. Mirabegron, the B3-adrenoreceptor agonist has emerged as an evidence-based alternative first or second line therapy. Two decades after its first clinical application for overactive bladder, intravesical botulinum toxin is now an important part of any clinician's armamentarium for refractory cases. Despite these therapeutic options many patients find therapies ineffective or have adverse events. This has resulted in ongoing developments in the understanding of overactive bladder, potential new drugs and combination therapies, which this paper intends to review.

Management of female urinary incontinence: A survey of urogynaecologists’ view on the NICE guideline

We conducted a survey to obtain the opinions of urogynaecologists regarding the National Institute for Health and Care Excellence or NICE 2013 urinary incontinence guideline and whether it would change their current practice. A closed format questionnaire was sent electronically to all members of the British Society of Urogynaecology or BSUG between January and March 2014. There were three major areas of disagreement. First, 70.2% of respondents disagreed that a multidisciplinary team review was necessary before invasive treatment for urinary incontinence. Second, 53.8% of respondents disagreed that preoperative urodynamic studies were not required in stress urinary incontinence diagnosed clinically. Third, 58.6% of respondents disagreed that oxybutynin, tolterodine and darifenacin should be used as first-line drug therapy for overactive bladder. The questionnaire demonstrates that there are significant concerns leading to more than a third of respondents not altering their current practice in line with the entire guideline.

Drug therapy for overactive bladder

Drug therapy for overactive bladder

Alternative therapies for overactive bladder: Cannabis and urge incontinence

Current drug therapies for overactive bladder (OAB) can produce variable outcomes and bothersome side effects, resulting in poor compliance. In patients with neurogenic detrusor overactivity and urge incontinence, evidence of a beneficial effect with oral cannabinoids is emerging. The rationale for their use was the discovery of cannabinoid receptors (CB1 and CB2), with CB1 receptors at various sites, including the brain and bladder, although the distribution of CB2 receptors is more limited. Cannabinoids also bind to vanilloid receptors, which have been the basis for intravesical therapies, such as capsaicin and resiniferatoxin. However, the use of capsaicin is limited by its pungency, whereas resiniferatoxin is limited by difficulties in delivery. Cannabinoids appear to work at several levels centrally and peripherally on detrusor smooth muscle, suggesting that they might produce similar effects in patients with neurogenic and nonneurogenic OAB. Large clinical trials of cannabinoids without psychotropic effects are required.

A review of adherence to drug therapy in patients with overactive bladder

Drug therapy for overactive bladder (OAB) is associated with improvements in symptoms and quality of life, but the short- and long-term adherence and persistence is suboptimal. In this review we outline methods of measuring, and factors affecting, adherence to pharmacotherapy in patients with OAB. Clinical practice suggests that adherence rates reported in clinical trials are much greater than in real practice. Factors affecting adherence include psychological and social variables that might alter patients' perception of the benefits of taking medication, and the effect of comorbidity and polypharmacy. Whilst there is some evidence that lack of efficacy and side-effects are contributory, these additional factors are also important.

Critical Evaluation of the Efficacy and Safety of Anticholinergics in Overactive Bladder

Antimuscarinic agents are the primary pharmacologic treatment of overactive bladder (OAB), and objective clinical data are available in a range of formats including head-to-head studies, systematic reviews and adjusted indirect comparisons. This paper reexamines the various data available on the safety and efficacy of the antimuscarinics. Clinical studies determine whether one treatment is better than another, rather than examining which treatment is best for the individual patient. Favourable treatment outcome may not be attained because of unrealistic expectations of the patient, who may also be dissatisfied with the complications of the treatment. Comparisons between clinical studies on drug therapy for OAB may be complicated by the high placebo response rates. Variations exist in the study populations in terms of symptom severity and tolerance of adverse events, and the diverse methods of assessment employed. Apart from head-to-head studies, meta-analyses can be employed to compare different classes of drugs (lumping method) or individual drugs (splitting method) by pooling of clinical data. The adjusted indirect comparison method has been developed as a method to allow the outcome of two different trials to be compared. Overall, data from clinical trials indicate that the commonly used antimuscarinics have different tolerability and safety profiles but broadly similar efficacy profiles. Consequently, therapy should be tailored to individual patient needs rather than one drug fits all.

Drug therapies for overactive bladder

The cornerstones of current drug therapy for overactive bladder are anticholinergic drugs; oxybutinin or tolterodine extended-release preparations are commonly prescribed as first-line treatments.

Advances in Managing Overactive Bladder

Overactive bladder (OB), formerly known as urge incontinence, is the most common type of urinary incontinence. The appropnate management of OB is more important than ever since the number of persons with OB is expected to increase with the growing elderly population, the group at highest risk for OB. At the same time new drugs are available that are generally as effective and better tolerated than the current "gold standard" drug therapy. To facilitate the selection of optimum pharmacotherapy for OB, the important distinguishing properties of the traditional and new drug therapies for OB will be reviewed.