Comparative analysis of real-world adherence and persistence patterns with vibegron, mirabegron, and anticholinergics in patients with overactive bladder: A retrospective claims study.

INTRODUCTION: Vibegron is a selective ß3-adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics. MATERIALS AND METHODS: This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up. RESULTS: The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001). CONCLUSION: In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics.

The Ideal Neurogenic Bladder Management Team.

This article discusses the ideal neurogenic bladder management team for patients who have neurogenic lower urinary tract dysfunction (NLUTD). It emphasizes the importance of a diverse team, including urologists, physiatrists, neurologist and others, working collaboratively to prevent complications and enhance patient outcomes. Owing to the unique nuances of the various neurologic conditions and patterns of NLUTD dysfunction, the roles of different specialists in the interdisciplinary team are outlined. This article describes 3 team models: multidisciplinary, interdisciplinary, and transdisciplinary, highlighting the benefits of collaborative approaches.

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.

Efficacy and safety of an alternative onabotulinumtoxinA injection paradigm for refractory overactive bladder.

AIMS: In studies utilizing a 20-injection-site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10-injection-site paradigm targeting the lower bladder. METHODS: In this phase 4, double-blind, parallel-group study, patients with OAB and urinary incontinence (UI) for ≥6 months with ≥3 episodes of urinary urgency incontinence (no more than 1 UI-free day) and ≥8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder. RESULTS: Of 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double-blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (-2.9) versus placebo (-0.3) (least squares mean difference [LSMD]: -2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75-50.37]), ≥75% (OR: 7.25 [2.00-26.29]), and ≥50% improvement (OR: 4.79 [1.87-12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: -2.24, p < 0.0001), nocturia (LSMD: -0.71, p = 0.0004), and urgency (LSMD: -2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23-52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double-blind period; no females used CIC during the double-blind period. Commonly reported adverse events (≥5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo. CONCLUSION: In patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC.

Risk factors for urinary tract infections associated with lower quality of life among intermittent catheter users.

BACKGROUND: Evidence shows that intermittent catheterisation (IC) for bladder emptying is linked to urinary tract infections (UTIs) and poor quality of life (QoL). AIM: To investigate the association between UTI risk factors and QoL and patient-reported UTIs respectively. METHODS: A survey was distributed to IC users from 13 countries. FINDINGS: Among 3464 respondents, a significantly poorer QoL was observed when experiencing blood in the urine, residual urine, bowel dysfunction, recurrent UTIs, being female, and applying withdrawal techniques. A lower UTI risk was found when blood was not apparent in urine (RR: 0.63; 95% CI: 0.55-0.71), the bladder was perceived empty (RR: 0.83; 95% CI: 0.72-0.96), not having bowel dysfunction (RR: 0.86; 95% CI: 0.76-0.98), and being male (RR: 0.70; 95% CI: 0.62-0.79). CONCLUSION: This study underlines the importance of risk factors and their link to QoL and UTIs, highlighting the need for addressing symptoms before UTIs become problematic.

New Intermittent Urinary Micro-Hole Zone Catheter Shows Enhanced Performance in Emptying the Bladder: A Randomised, Controlled Crossover Study.

Urinary tract infections (UTIs) are common and troublesome complications of clean intermittent catheterisation (CIC) in individuals suffering from incomplete bladder emptying, which may exacerbate the underlying disease and lead to hospitalisation. Aside from the design of the intermittent catheter and its handling, a recent review highlighted residual urine as one of several UTI risk factors. A new urinary intermittent catheter with multiple micro-holes has been developed for improved bladder emptying. In a controlled crossover study, adult male CIC users were randomised for a health care professional-led catheterisation with the new micro-hole zone catheter (MHZC) and a conventional eyelet catheter (CEC) in two individual test visits to compare the number of flow-stops and the residual urine at the first flow-stop as co-primary endpoints. In 42 male CIC users, the MHZC resulted in significantly fewer flow-stop episodes compared to the CEC (mean 0.17, 95% CI [0.06, 0.45] vs. mean 1.09, 95% CI [0.75, 1.6], respectively; p < 0.001) and significantly less residual urine at the first flow-stop (mean 5.10 mL, SE [1.14] vs. mean 39.40 mL, SE [9.65], respectively; p < 0.001). No adverse events were observed in this study. The results confirm the enhanced performance of the MHZC compared to a CEC, ensuring an uninterrupted free urine flow with no need to reposition the catheter until the bladder is thoroughly empty.

Treatment of neurogenic detrusor overactivity and overactive bladder with Botox (onabotulinumtoxinA): Development, insights, and impact.

Neurogenic detrusor overactivity (NDO) is a complication of multiple sclerosis, spinal cord injury (SCI), stroke, head injury, and other conditions characterized by damage to the upper motor neuronal system. NDO often leads to high bladder pressure that may cause upper urinary tract damage and urinary incontinence (UI). Prior to the use of onabotulinumtoxinA, oral anticholinergics and surgical augmentation cystoplasty were the treatment options. Overactive bladder (OAB) is non-neurogenic and affects a much larger population than NDO. Both NDO and OAB negatively impact patients' quality of life (QOL) and confer high health care utilization burdens. Early positive results from pioneering investigators who injected onabotulinumtoxinA into the detrusor of patients with SCI caught the interest of Allergan, which then initiated collaborative clinical trials that resulted in FDA approval of onabotulinumtoxinA 200U in 2011 for NDO and 100U in 2013 for patients with OAB who inadequately respond to or are intolerant of an anticholinergic. These randomized, double-blind, placebo-controlled trials for NDO showed significant improvements in UI episodes, urodynamic parameters, and QOL; the most frequent adverse events were urinary tract infection (UTI) and urinary retention. Similarly, randomized, double-blind, placebo-controlled trials of onabotulinumtoxinA 100U for OAB found significant improvements in UI episodes, treatment benefit, and QOL; UTI and dysuria were the most common adverse events. Long-term studies in NDO and OAB showed sustained effectiveness and safety with repeat injections of onabotulinumtoxinA, the use of which has profoundly improved the QOL of patients failing anticholinergic therapy and has expanded the utilization of onabotulinumtoxinA into smooth muscle.

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.

Neuro-Urology: Call for Universal, Resource-Independent Guidance.

Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines.

AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2).

BACKGROUND: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. OBJECTIVE: To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport®; Ipsen Ltd.) according to etiology of NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). INTERVENTION: Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). RESULTS AND LIMITATIONS: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48-62 weeks across doses) than those with SCI (39-44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. CONCLUSIONS: AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. PATIENT SUMMARY: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence.

Long-term efficacy and safety of vibegron versus mirabegron and anticholinergics for overactive bladder: a systematic review and network meta-analysis.

Background: Few randomized controlled trials evaluate the long-term efficacy and safety of pharmacotherapy for overactive bladder (OAB). This network meta- analysis compares the long-term (52-week) efficacy and safety of vibegron, mirabegron and anticholinergics for the treatment of OAB. Methods: A systematic literature review and network meta-analysis were conducted following PRISMA guidelines using MEDLINE, Embase and Cochrane Central Register of Controlled Trials and terms related to OAB. Efficacy outcomes included change from baseline to week 48-52 in mean daily total urinary incontinence (UI) episodes, mean daily number of micturitions and volume voided/micturition. Efficacy outcomes were analysed using Bayesian models. Commonly reported adverse events (AEs) are described. Results: Of 2098 hits retrieved, 5 publications and 1 study report describing 5 unique randomized controlled trials were included in the analyses. Mean (95% credible interval) change from baseline in total UI episodes for vibegron 75 mg (-2.2; -2.9 to -1.5) showed a significantly greater reduction than mirabegron 50 mg (-1.3; -1.9 to -0.8) and tolterodine 4 mg extended release (-1.6; -2.1 to -1.1). No significant differences were observed between vibegron and comparators for daily micturitions or volume voided/micturition. Within the manuscripts, the 4 most common AEs (range) for anticholinergics included dry mouth (5.2-90.0%), constipation (7.7-65.0%), blurred vision (3.8-35.0%) and hypertension (8.6-9.6%); the 4 most commonly reported AEs for ß3-adrenergic agonists included hypertension (8.8-9.2%), urinary tract infection (5.9-6.6%), headache (5.5%) and nasopharyngitis (4.8-5.2%). Conclusion: Vibegron was associated with significantly greater improvement in daily total UI episodes at 52 weeks than mirabegron and tolterodine. When reported, the most common AE for anticholinergics was dry mouth and for ß3-adrenergic agonists was hypertension. Hypertension incidence was similar between drug classes.

Vibegron for the Treatment of Patients with Dry and Wet Overactive Bladder: A Subgroup Analysis from the EMPOWUR Trial.

Background: Overactive bladder (OAB) is characterized by urgency and frequency with (OAB wet) or without (OAB dry) urge urinary incontinence (UUI). In the phase 3 EMPOWUR trial, vibegron-a selective ß 3-adrenergic receptor agonist for the treatment of OAB-significantly improved daily number of urgency episodes and micturitions vs. placebo (P < 0.01). These post hoc analyses aimed to compare the efficacy of vibegron vs. placebo in OAB dry and wet populations. Methods: Patients were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, for 12 weeks. Baseline criteria for OAB dry included an average of ≥8 micturitions, ≥3 urgency episodes, and <1 UUI episode per diary day and for OAB wet included an average of ≥8 micturitions and ≥1 UUI episode per diary day. Change from baseline in mean daily number of urgency episodes and micturitions was assessed in both populations. Results: Of the 1463 patients included in the full analysis set, 336 (23%) had OAB dry (vibegron, N = 123; placebo, N = 115; and tolterodine, N = 98), and 1127 (77%) had OAB wet (vibegron, N = 403; placebo, N = 405; and tolterodine, N = 319). Vibegron was associated with significant reductions (95% CIs of the least squares mean differences [LSMD] does not include 0) from baseline at week 12 vs. placebo in mean daily urgency episodes for the dry (LSMD [95% CI], ‒1.0 [‒2.0, ‒0.1]) and wet (‒0.6 [‒1.0, ‒0.1]) populations. Vibegron was associated with significant reductions from baseline at week 12 vs. placebo in mean daily micturitions for the dry (LSMD [95% CI], ‒0.8 [‒1.5, ‒ 0.1]) and wet (‒0.5 [‒0.8, ‒0.1]) populations. There were no significant differences in either outcome between tolterodine and placebo for either the dry or wet populations in this study. Conclusions: In this subgroup analysis from the EMPOWUR trial, vibegron was associated with significant reductions compared with placebo in urgency episodes and micturitions in both the OAB dry and wet populations, suggesting that vibegron is similarly efficacious for these endpoints in patients with and without UUI. This trial is registered with NCT03492281.

The relative importance of different consequences of nocturnal enuresis among older women: A conjoint analysis experiment.

INTRODUCTION: Adult nocturnal enuresis (NE) is an understudied and bothersome condition. Our objective was to conduct a conjoint analysis experiment to better understand the relative importance of NE consequences in older women. METHODS: We developed a conjoint analysis survey that included four attributes related to NE (awakening at night, feeling rested in the morning, restricting fluid before bed, and wet perineal skin). We performed a prospective cross-sectional online study of women >62 years of age with NE using Sawtooth Software. Patients completed baseline questions, the International Consultation on Incontinence Questionnaire-nocturia Quality of Life (ICIQ-NqoL), and the conjoint analysis experiment. Hierarchical Bayes random effects regression analysis was used to determine the relative importance of the four attributes. RESULTS: A total of 200 women with a mean age of 71 years completed the study. The most common management of NE was diapers/pads (132/200). Approximately half of the participants experienced NE several times a week or nightly (101/200). The most important attribute was the frequency of being awakened at night (34, standard deviation [SD]: 16) and the frequency of feeling rested in the morning (32, SD: 15). Limiting drinking before bed (18, SD: 12) and wet groin skin (16, SD: 10) had significantly lower importance scores (p < 0.05). Age, sleeping with a partner in bed, body mass index, NE severity score, and the ICIQ-NqOL score were not significantly associated with any of the importance scores. CONCLUSIONS: Older women with NE place significantly more importance on the frequency of awakening at night, and feeling rested in the morning and lesser importance on associated lifestyle or physical manifestations of NE.

Efficacy and Safety of AbobotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Incontinence Performing Regular Clean Intermittent Catheterization: Pooled Results from Two Phase 3 Randomized Studies (CONTENT1 and CONTENT2).

BACKGROUND: For patients with neurogenic detrusor overactivity incontinence (NDOI), treatment with oral medications is often unsatisfactory. OBJECTIVE: To assess the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) for NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two randomized, double-blind phase 3 studies (CONTENT1, NCT02660138; CONTENT2, NCT02660359) enrolled patients with NDOI who were regularly performing clean intermittent catheterization (CIC) and were inadequately managed with oral therapy. Pooled results from the first placebo-controlled treatment cycle are reported. INTERVENTION: Patients received injections of aboBoNT-A 600 U (n = 162) or 800 U (n = 161) or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the mean change from baseline in NDOI episodes per week at week 6. Secondary endpoints reported are the proportion of patients with no NDOI episodes, the volume per void, urodynamic parameters, and quality of life (QoL). Safety was also assessed. Statistical analyses were conducted for the pooled study populations (each aboBoNT-A dose vs placebo). RESULTS AND LIMITATIONS: At week 6, NDOI episodes per week were significantly reduced in each aboBoNT-A group versus placebo (both p < 0.001) and the volume per void had significantly increased. Approximately one-third of patients in each aboBoNT-A dose group reported no NDOI episodes versus 3% of patients in the placebo group. Reductions in urinary incontinence (UI) were reflected in significantly greater improvements in UI-related QoL in the aboBoNT-A groups versus placebo. Urodynamic parameters (bladder capacity and detrusor pressure) were significantly improved with each aboBoNT-A dose versus placebo. Each aboBoNT-A dose was well tolerated. Symptomatic urinary tract infection was the most frequent treatment-emergent adverse event, with incidence comparable across the aboBoNT-A and placebo groups. The studies were terminated prematurely owing to slow recruitment and were not designed for statistical comparison between the two aboBoNT-A doses. CONCLUSIONS: Intradetrusor aboBoNT-A is an effective treatment and alternative option for patients with NDOI who have an inadequate response to oral anticholinergics and are already performing CIC. PATIENT SUMMARY: In patients with bladder muscle overactivity caused by neurological conditions (multiple sclerosis or spinal cord injury) and resulting in urinary incontinence, abobotulinumtoxinA injections improved their symptoms and bladder function, with no unexpected effects.

General and bladder-related quality of life: A focus on women living with spinal cord injury.

OBJECTIVE: To compare bladder symptoms, and urinary and overall quality of life (QOL) among women and men after Spinal cord injury (SCI), and to describe specific aspects of QOL among women with SCI. METHODS: We used data from a prospective, multi-center, and cross-sectional study that was carried out from May 2019 to September 2020. Clinical and demographic details were obtained and participants completed two patient reported outcomes: the neurogenic bladder symptoms score-short form (NBSS-SF, which measures bladder symptoms and QOL) and the SF-12 (which measures overall physical and mental health QOL). RESULTS: Our cohort included 135 women and 210 men with SCI. Among the women, the median age was 50, and 40% had a cervical SCI. For general QOL, women with SCI had physical functioning scores similar to men, but lower mental health scores on the SF-12 (46.85 vs. 49.76, p = 0.01). Women had significantly worse overall NBSS (10.76 vs. 9.08, p < 0.001) and NBSS continence domain scores (4.71 vs. 3.66, p < 0.001) compared to men. There were significant differences between overall QOL measures, and bladder symptoms based on bladder management techniques among the women. NBSS-SF symptom scores were better among women who used overactive bladder medications compared to women who did not (8.43 vs. 11.9, p = 0.02) and NBSS-SF QOL domain scores were significantly better among women who underwent surgery and those that used overactive bladder medications. CONCLUSIONS: Women have more bladder symptoms (specifically incontinence) compared to men. Symptom burden and overall QOL vary among women who use different bladder management techniques and treatments.

An Evaluation of the Efficacy and Safety of Vibegron in the Treatment of Overactive Bladder.

Pharmacologic treatment for overactive bladder (OAB), which is characterized by bothersome symptoms such as urgency and urge urinary incontinence (UUI), includes anticholinergics and ß3-adrenergic receptor agonists. Anticholinergics are associated with adverse effects including dry mouth, constipation, cognitive impairment, and increased risk of dementia. Therefore, the drug class of ß3-adrenergic receptor agonists may represent an effective, safe treatment option. Vibegron, a ß3-adrenergic receptor agonist, was approved for use in Japan (2018) and the United States (2020). Over the past 3 years, 2 phase 3 trials (EMPOWUR, EMPOWUR extension) have been conducted with once-daily vibegron 75 mg for the treatment of OAB, and additional secondary and subgroup analyses have detailed the efficacy and safety of vibegron. In the international phase 3 EMPOWUR trial, treatment with vibegron was associated with significant improvements compared with placebo in efficacy outcomes of micturition frequency, UUI episodes, urgency episodes, and volume voided as early as week 2 that were sustained throughout the 12-week trial. The 40-week EMPOWUR extension study, following the 12-week treatment period, demonstrated sustained efficacy in patients receiving vibegron for 52 weeks. Treatment with vibegron was also associated with improvements in patient-reported measures of quality of life. Across studies, vibegron was generally safe and well tolerated. A separate, dedicated ambulatory blood pressure monitoring study showed that treatment with vibegron was not associated with clinically meaningful effects on blood pressure or heart rate. Across all studies, vibegron was efficacious, safe, and well tolerated and thus represents a valuable treatment option for patients with OAB. Here, nearly 1 year after US approval, we review the published data on efficacy and safety of vibegron 75 mg for the treatment of OAB.

Interpretation of the Meaningfulness of Symptom Reduction with Vibegron in Patients with Overactive Bladder: Analyses from EMPOWUR.

INTRODUCTION: Reductions in bothersome symptoms of overactive bladder (OAB) demonstrate improvement in clinical trials, but patient perception of meaningfulness of such improvement is lacking. In the 12-week phase 3 EMPOWUR trial, vibegron significantly reduced average daily number of micturitions, urgency episodes, and urge urinary incontinence (UUI) episodes vs placebo (P < 0.01 each). This analysis assessed meaningfulness of reductions in clinical endpoints observed in EMPOWUR using patient perception of improvement. METHODS: An anchor-based approach using Patient Global Impression of Change (PGI-C) applied to phase 2 data allowed predefining phase 3 responder definitions. To confirm in phase 3, median change from baseline at week 12 in average daily number of micturitions, urgency episodes, and UUI episodes was generated for each PGI-C category and pooled across treatments. Based on predefined meaningful responder definitions, percentages of patients achieving ≥ 15% reduction in micturitions (post hoc), ≥ 50% reduction in urgency episodes (predefined), and ≥ 75% (predefined) and ≥ 90% (post hoc) reduction in UUI episodes were determined for patients receiving vibegron or placebo. RESULTS: Across treatments, for micturitions, urgency episodes, and UUI episodes, median change from baseline to week 12 increased with greater subjective improvement based on PGI-C scores, and median reductions pooled across treatment groups were higher than the responder definitions that patients perceived as improved. Significantly more patients receiving vibegron vs placebo achieved ≥ 15% reduction in micturitions (56.3% vs 44.6%, respectively), ≥ 50% reduction in urgency episodes (39.5% vs 32.8%), ≥ 75% reduction in UUI episodes (49.3% vs 32.8%), and ≥ 90% reduction in UUI episodes (35.2% vs 23.5%) at week 12 (P < 0.05 each). CONCLUSION: Significantly more patients treated with vibegron vs placebo in EMPOWUR achieved meaningful reductions in micturitions, urgency episodes, and UUI episodes that were associated with patient-perceived improvement. Results of these analyses support the meaningfulness of reductions in clinical endpoints observed in the 12-week EMPOWUR trial. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier, NCT03492281.

The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Treatment and Follow-up.

PURPOSE: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of adult patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. CONCLUSIONS: NLUTD patients may undergo non-surgical and surgical treatment options depending on their level of risk, symptoms, and urodynamic findings. Appropriate follow-up, primarily based on their risk stratification, must be maintained after treatment.

The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Diagnosis and Evaluation.

PURPOSE: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. This Guideline is for adult patients with NLUTD and pediatric NLUTD will not be discussed. CONCLUSIONS: NLUTD patients should be risk-stratified as either low-, moderate-, high-, or unknown-risk. After diagnosis and stratification, patients should be monitored according to their level of risk at regular intervals. Patients who experience new or worsening signs and symptoms should be reevaluated and risk stratification should be repeated.