Efficacy of transcutaneous electrical nerve stimulation combined with mirabegron therapy compared with mirabegron monotherapy for overactive bladder: a prospective randomized controlled study.

PURPOSE: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). METHODS: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. RESULTS: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. CONCLUSIONS: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. TRIAL REGISTRATION NUMBER: ChiCTR2400080528 (31.01.2024, retrospectively registered).

Safety and efficacy of beta-3 adrenergic agonists in treating neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

PURPOSE: To evaluate efficacy and safety of beta-3 adrenergic agonists in adults with neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS: According to a protocol (CRD42022350079), we searched multiple data sources for published and unpublished randomized controlled trials (RCTs) up to 2nd August 2022. Two review authors independently screened studies and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence (CoE). RESULTS: We found data to inform two comparisons: beta-3 adrenergic agonists versus placebo (4 RCTs) and anticholinergics (2 RCTs). Only mirabegron was used for intervention in all included studies. Compared to placebo, beta-3 adrenergic agonists may have a clinically unimportant effect on urinary symptoms score (mean difference [MD] -2.50, 95% confidence interval [CI] -4.78 to -0.22; I²=92%; 2 RCTs; 192 participants; low CoE) based on minimal clinically important difference of 3. We are very uncertain of the effects of beta-3 adrenergic agonists on quality of life (MD 10.86, 95% CI 1.21 to 20.50; I²=41%; 2 RCTs; 98 participants; very low CoE). Beta-3 adrenergic agonists may result in little to no difference in major adverse events (cardiovascular adverse events) (risk ratio 0.57, 95% CI 0.14 to 2.37; I²=0%; 4 RCTs; 310 participants; low CoE). Compared to anticholinergics, no study reported urinary symptom scores and quality of life. There were no major adverse events (cardiovascular adverse events) in either study group (1 study; 60 participants; very low CoE). CONCLUSIONS: Compared to placebo, beta-3 adrenergic agonists may have similar effects on urinary symptom scores and major adverse events. There were uncertainties about their effects on quality of life. Compared to anticholinergics, we are either very uncertain or have no evidence about urinary symptom scores, quality of life, and major adverse events.

The impact of pharmacotherapy on sexual function in female patients being treated for idiopathic overactive bladder: a systematic review.

BACKGROUND: Overactive bladder (OAB) is a condition defined by urgency with or without incontinence which disproportionately affects female patients and has a negative impact on sexual enjoyment and avoidance behaviour. Pharmacotherapy can be considered one of the main options for treating OAB. This research set out to determine the impact of pharmacotherapy on sexual function in females with OAB. METHODS: This research used the robust methodology of a systematic review. The clinical question was formulated using the PICO (population, intervention, control, and outcomes) format to include females being treated with pharmacotherapy (anticholinergics or beta-3 adrenergic agonists) for idiopathic OAB with the use of a validated questionnaire assessing self-reported sexual function at baseline and post-treatment. The review incorporated the MEDLINE, PubMed and EMBASE databases. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) appraisal tool was used to guide the review process. Two reviewers worked independently in screening abstracts, deciding on the inclusion of full-texts, data extraction and risk of bias assessment. RESULTS: In female patients with OAB, pharmacotherapy does seem to offer at least partial improvement in self-reported sexual function outcomes after 12 weeks of therapy. Still, the value of this finding is limited by an overall poor quality of evidence. Patients with a higher degree of bother at baseline stand to benefit the most from treatment when an improvement within this health-related quality of life domain is sought. CONCLUSION: This research should form the basis for a well-conducted randomized controlled study to accurately assess sexual function improvements in females being treated with pharmacotherapy for OAB.

The ß3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease.

X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the ß3-adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the ß3-AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X-NDI. Here we demonstrate that the ß3-AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X-NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow-release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X-NDI mice. Taken together, these data suggest that human ß3-AR agonists might represent an effective possible treatment strategy for X-NDI.

Real-World Adherence to and Persistence with Vibegron in Patients with Overactive Bladder: A Retrospective Claims Analysis.

INTRODUCTION: Vibegron is a ß3-adrenergic receptor agonist approved for overactive bladder (OAB). This analysis assessed real-world adherence and persistence with vibegron in patients with OAB, along with demographics and clinical characteristics associated with adherence and persistence. METHODS: This retrospective study used the Optum Research Database to identify patients treated with vibegron from April 2021 to August 2022 (identification period). Patients had ≥ 60 days of continuous pharmacy coverage in a commercial or Medicare Advantage plan following the index fill (follow-up). Adherence was assessed as proportion of days covered (PDC) from index to end of follow-up and was defined as PDC ≥ 80%. Persistence was measured as days to discontinuation of therapy (30-day gap) or end of follow-up. Data for adherence and persistence are presented descriptively. Characteristics associated with adherence and persistence were analyzed using multivariable models among patients with medical and pharmacy benefits during the 90 days before index (baseline). RESULTS: Overall, 9992 patients had a vibegron claim during the identification period; 9712 had ≥ 2 months of follow-up. Mean (SD) age was 74.2 (10.7) years; 68.2% were female. Mean (SD) PDC was 0.64 (0.34). Median (95% confidence interval) persistence was 142 (132-153) days. Of the 5073 patients who were ≥ 18 years old with continuous baseline pharmacy and medical benefits ≥ 90 days before index, 2497 (49.2%) were adherent. Patients were more likely to be adherent and persistent if they received a greater days' supply for the index fill and had baseline medication count ≥ 6. Patients were more likely to discontinue if their index copay was > $45. CONCLUSION: Nearly half of the patients initiating vibegron were adherent. Factors associated with adherence and persistence were more likely to be related to prescribing practices than patient characteristics. These results suggest it may be best to follow up with patients approximately 4 to 5 months after initiating treatment with vibegron.

Vibegron is a newer drug for treating overactive bladder. Vibegron was safe and worked well in clinical trials. However, there is no information on use of vibegron in a real-world population that is not a clinical trial. This study looked at how consistently and how long patients took vibegron after starting it. It also looked at what was common in patients who took vibegron consistently. To do this, the study used pharmacy prescription data from April 2021 to August 2022. It examined adherence to the study medication for each patient. Adherence is how many days patients had medication on hand compared to how long they were followed. The study also looked at persistence to the study medication. Persistence is how long a patient takes a medication before they stop taking it. Researchers then examined if there were reasons a patient may or may not take vibegron as prescribed. The study included prescription data for 9712 patients. The average age was 74 years and 68% of patients were female. Patients had their medication 64% of the time (adherence). On average, patients took their medication for 142 days before stopping (persistence). Patients had better adherence and persistence if they received a larger supply of medication at the pharmacy when first prescribed the medication and if they had more medications overall. Patients' age and gender did not affect adherence and persistence. Vibegron may be a good option for patients with overactive bladder. Follow-up with a provider may be considered 4 to 5 months after starting vibegron.

Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

What is the best first choice oral drug therapy for OAB?

AIMS: The management of overactive bladder (OAB) involves lifestyle changes and conservative measures in the first instance with the use of liquid/dietary advice, weight loss, and bladder training. Thereafter oral pharmacotherapy is instigated in symptomatic patients. Antimuscarinics and beta 3 agonists form the main classes of drug therapy in this field. Views on what is the best first line OAB treatment is changing based on recent evidence and adverse event profiles of these medications. METHODS: At the ICI-RS meeting 2023, Bristol, UK this topic was discussed and debated as a proposal. The following article summarizes the concepts presented that day as well as the interactive discussion that took place thereafter. RESULTS: OAB guidelines are moving in many circumstances to an either antimuscarinic or beta 3 agonist approach based on patient factors. Several studies have raised concerns on the long-term impact of antimuscarinics, in relation to cognition, dementia, cardiovascular events, and mortality all related to antimuscarinic load. Neither antimuscarinics nor beta 3 agonists have good persistence and adherence rates in the medium to long term. Several barriers also exist to prescribing including guidelines recommending utilizing drugs with the lowest acquisition cost and "step therapy." A newer approach to managing OAB is personalized therapy in view of the many possible etiological factors and phenotypes. These concepts are highlighted in this article. CONCLUSIONS: Current oral pharmacotherapy in managing OAB is limited by adverse events, adherence and persistence problems. Both antimuscarinics and beta 3 agonists are efficacious but most clinical trials demonstrate significant placebo effects in this field. Personalizing treatment to the individual seems a logical approach to OAB. There is a need for better treatments and further studies are required of existing treatments with high quality longer term outcomes.

Factors Influencing Medication Selection for Management of Overactive Bladder: Trends and Insights From AUA Quality Registry.

OBJECTIVE: To determine how a patient's demographics, including insurance type, race/ethnicity, gender, and age, may impact the choice of medication prescribed for overactive bladder (OAB). METHODS: We queried the AUA Quality Registry for adults between 2014 and 2020 with a diagnosis of OAB for >1year, excluding neurogenic causes. Variables included age, race/ethnicity, gender, insurance type, medication first prescribed, year of prescription, provider metropolitan status, and provider practice type. Primary outcome was which factors were associated with increased odds of beta-3 prescription as first medication choice. RESULTS: We found 1,453,566 patients with OAB, 641,122 (44.1%) with complete data. Of these, 112,021 (17.5%) were prescribed medication. On multivariate analysis, patients with Medicaid, Medicare, and other/self-pay insurance were less likely to receive a beta-3 vs an anticholinergic compared to private or military insurance. Compared to white patients, Asian, Black, and other races were less likely to receive a beta-3, as were patients outside of metropolitan areas. Age >50, prescriptions after 2014, and nonacademic settings were associated with increased odds of beta-3 prescription. There was no difference between genders. CONCLUSION: Many nonclinical factors, including insurance type and race, may affect which medication is first prescribed for OAB. This is useful for practicing urologists and may help lower barriers to beta-3 prescription through policy change and advocacy.

Effects of a new selective ß3 -adrenoceptor agonist, vibegron, on bladder and urethral function in a rat model of Parkinson's disease.

OBJECTIVES: Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel ß3 -adrenoceptor agonist approved for the treatment of overactive bladder. However, how ß3 -adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease. METHODS: In a rat model of Parkinson's disease induced by unilateral 6-hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity. RESULTS: Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter-contraction interval (p < .05) and reduced voiding pressure (p < .01). However, no significant effects on urethral function were observed. CONCLUSIONS: The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of ß3 -adrenoceptor agonists.

Plain language summary of safety and symptom improvement with vibegron in people with overactive bladder: results from the EMPOWUR study.

What is this summary about? This is a plain language summary of an article originally published in the Journal of Urology. Overactive bladder (also called OAB) has been treated with the same type of medicine for more than 40 years. Vibegron is in a newer class of medicine for treating overactive bladder called beta-3 adrenergic receptor agonists. The EMPOWUR study was a phase 3 clinical trial that looked at whether vibegron was safe and improved symptoms in people with overactive bladder. Vibegron was approved by the US Food and Drug Administration (also called the FDA) based in part on the results of this study. What were the results? Participants of the EMPOWUR study who took vibegron showed an improvement in their overactive bladder symptoms. These symptoms include the number of urinations (peeing), the urgent need to urinate, and accidental urination (bladder leaks). After 12 weeks, participants who took vibegron had significantly greater improvements than participants who took placebo. What do the results mean? This study suggests that vibegron could safely improve symptoms in people with overactive bladder. Clinical Trial Registration: NCT03492281 (ClinicalTrials.gov).

[Drugs for Neurogenic Bladder Dysfunction].

Urinary dysfunction includes an overactive bladder (OAB), post-void residual (PVR)/retention, or both entities. Brain diseases cause OAB, peripheral neuropathies are associated with significant PVR/retention, and multisystem atrophy/spinal cord diseases result in a combination of OAB and PVR/retention. Selective beta 3 adrenergic receptor agonists or anticholinergic agents are the first-choice treatment for OAB and clean intermittent self-catheterization, alpha-blocker and cholinergic stimulant therapy for significant PVR/retention. These therapies may be useful to maximize patients' quality of life and prevent serious complications, such as urosepsis or kidney dysfunction.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

Cold stress-induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of a M3 -muscarinic antagonist and a ß3 -adrenergic agonist.

OBJECTIVES: Goto-Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M3 -muscarinic receptor antagonist and a ß3 -adrenergic receptor agonist. METHODS: Ten-week-old female GK rats were fed a high-fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle, the M3 -muscarinic receptor antagonist solifenacin, the ß3 -adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M3 -muscarinic and ß3 -adrenergic receptors were investigated. RESULTS: After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle-, solifenacin-, or mirabegron-treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M3 -muscarinic and ß3 -adrenergic receptors were detected, the expression of M3 -muscarinic receptor mRNA was significantly higher than that of ß3 -adrenergic receptor mRNA. CONCLUSIONS: The cold stress-induced bladder overactivity was not improved by either the M3 -muscarinic receptor antagonist or the ß3 -adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M3 -muscarinic antagonists and ß3 -adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.

Are ß3 -adrenoceptor gene polymorphisms relevant for urology?

AIMS: ß3 -adrenoceptors (ARs) are an important drug target for the treatment of overactive bladder syndrome (OAB) and are under investigation for other indications. The human ß3 -AR gene is polymorphic; an exchange of amino acid tryptophan (Trp) for arginine (Arg) in position 64 of the receptor protein is the most frequent and best-studied polymorphism. A narrative review on the impact of ß3 -AR polymorphisms on urological disease and its treatment is presented. RESULTS: Two out of four studies have reported that the 64Arg allele was found more frequently in subjects with OAB than in healthy controls. A large study in a highly selective population (men undergoing prostatectomy for cancer treatment) did not confirm this. On the other hand, studies examining symptom severity typically found little difference between 64Arg and 64Trp carriers. In vitro studies with endogenously expressed ß3 -AR reported a decreased lipolytic response in human adipose tissue. Studies with heterologously expressed receptors sometimes found a decreased responsiveness to agonists including ß3 -AR agonists, but others did not confirm that. CONCLUSIONS: The overall evidence points to carriers of the 64Arg genotype expressing fewer and/or hypofunctional ß3 -ARs and being associated with the presence of OAB but such findings were only detected inconsistently. If this hypofunctionality exists, the consequences may be of insufficient magnitude to allow a robust detection. Only adequately powered studies comparing responses with a ß3 -AR agonist in 64Arg carriers versus wild-type patients can address this.

Urodynamic evaluation of the efficacy of vibegron, a new ß3-adrenergic receptor agonist, on lower urinary tract function in children and adolescents with overactive bladder.

INTRODUCTION: Idiopathic overactive bladder (OAB) is defined as an urgency symptom with or without urge incontinence, which is not due to known neurological abnormalities. Since children present with variable symptoms, pediatric nonneurogenic idiopathic OAB is a condition that is difficult to diagnose and treat. Although there are few reports on bladder function in pediatric patients compared to adult patients, it can be useful for diagnosis. Antimuscarinic therapy is the pharmacological mainstay of OAB management. However, antimuscarinic use is limited by side effects and Insufficient effects. Vibegron, a new drug with a different mechanism of action (ß3-adrenoreceptor agonist), was recently introduced for treating OAB in adults but has not been studied in the pediatric population. OBJECTIVE: This study aimed to determine the efficacy and tolerability of vibegron in children and adolescents with idiopathic OAB. STUDY DESIGN: We conducted a retrospective study enrolling pediatric patients with OAB whose symptoms did not improve with behavioral therapy or pharmaceutical therapy. Efficacy and tolerability were assessed via a question, and patients underwent video-urodynamic testing before and during treatment with once-daily 50 mg vibegron. Statistical differences were evaluated using Wilcoxon matched-pairs signed-rank tests. RESULTS: Out of the 17 patients that were recruited, full study with two urodynamic studies were confirmed by 11 patients. OAB symptoms improved in 14 (82.4%) patients, and 3 patients discontinued treatment because of ineffectiveness. No patients discontinued treatment because of intolerance to vibegron. The median (IQR) first desire to void (133 [82-185]-161 [123-227] mL), bladder capacity (158 [136-238]-204 [150-257] mL), and bladder compliance (18.1 [9.1-76.7]-34.0 [30.0-82.3] mL/cm H2O) improved significantly post treatment compared to before treatment. Detrusor overactivity disappeared in one of the eight patients with this condition. The parameters of voiding function did not change significantly after the administration of vibegron. DISCUSSION: Treatment with vibegron significantly improved clinical and urodynamic parameters of pediatric OAB with no adverse effects. Little information is available regarding the feasibility of switching drugs when patients discontinue prior pharmacological therapy because of insufficient efficacy or poor tolerability in children. Vibegron may be a promising OAB treatment option with a better balance of efficacy and tolerability. CONCLUSIONS: Vibegron is an alternative agent for pediatric patients with idiopathic OAB for improving both subjective symptoms and lower urinary tract function. Future prospective randomized studies with larger sample sizes must be conducted to validate the results of the present study.

Mirabegron for overactive bladder in frail patients 80 years or over (HOKUTO study).

BACKGROUND: We assessed the efficacy and safety of mirabegron, a ß3-adrenoceptor agonist, in older adults (≥ 80 years old) with overactive bladder (OAB). METHODS: OAB patients aged ≥ 80 years were enrolled in this prospective, single-arm observational study. OAB was diagnosed based on the OAB symptom score (OABSS); i.e., a total score of ≥ 3 points and an urgency score of ≥ 2 points. Patients who received 50 mg mirabegron once daily were evaluated at the baseline and at 4, 8, and 12 weeks. The changes from the baseline in the OABSS, International Prostate Symptom Score (IPSS), OAB questionnaire (OAB-q) score, and Vulnerable Elders Survey (VES-13) score were determined. Adverse events, laboratory tests, 12-lead electrocardiography, the QT interval according to Fridericia's formula (QTcF), uroflowmetry, the post-void residual urine volume (PVR), and the Mini-Mental State Examination (MMSE) score were used to assess safety. RESULTS: Forty-three patients (median age: 84 years, range: 80-96 years) were examined. They had high rates of comorbidities and polypharmacy. Mirabegron significantly improved in total score of the OABSS, including urgency and urge incontinence. The total IPSS, IPSS quality-of-life (QOL) index, and OAB-q scores also significantly improved. Mirabegron improved in the VES-13 score. There were no significant changes in laboratory test values, uroflowmetry findings, PVR, the QTcF, or MMSE score. Two patients (4.7%) withdrew from the study after experiencing adverse events. CONCLUSIONS: Mirabegron was well tolerated and significantly improved in OAB symptoms, and QOL in older patients. Trial registration The present clinical study was approved by University of Yamanashi Institutional Review Board prior to study initiation (ID1447) and was retrospectively registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (UMIN000045996) on Nov 6, 2021.