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Introduction: Vibegron is a selective β 3 -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., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Introduction and Objectives: Medical treatments for overactive bladder (OAB) have proven efficacy in controlled trials. However, 1-year treatment persistence is reported to be as low as 25% for anticholinergics and 40% for β3 agonists. Real-world data on treatment continuation and treatment sequence is limited. Therefore, we aimed to study treatment persistence trends in women initiated on OAB medications., Materials and Methods: We used advanced data-mining techniques to query the largest regional provider's medication purchase database, dispensing for patients, for all women initiating OAB pharmacotherapy between 2010 and 2020. Treatment persistence was measured as days in which the patient was in possession of medication and nonpersistence was defined as prescription nonrefilling for 90 days. We employed a Sankey diagram to explore trends in OAB medication acquisition and treatment sequence. We compared treatment persistence using Kaplan-Meier survival curves and pairwise log-rank analysis., Results: Here, 46 079 women made 791 681 unique claims of OAB medications. Only 39% of the patients tried more than one OAB formulation, including dose change. The overall persistence rate for all drugs was 55% in 30 days, 46% in 90 days, and 37% per year. The persistence rate for Mirabegron at 30 days was 54%, 42% at 90 days, and 17% at 1 year. Overall, persistence rates were unchanged when stratifying by the time Mirabegron insurance acceptance into coverage (p > 0.05)., Conclusions: Real-world OAB pharmacotherapy persistence rates are lower than previously reported. The introduction of Mirabegron did not seem to improve these rates or affect the treatment sequence., (© 2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Introduction: Overactive bladder (OAB) and frailty are independently associated with patient burden. However, economic burden and treatment-taking behavior have not been well characterized among frail patients with OAB, which, given the varying safety and tolerability profiles of available treatments, is crucial., Objectives: To assess costs, health care resource utilization, treatment-taking behavior (persistence and adherence) to OAB medication in older, frail OAB patients., Methods: This was a retrospective cohort study using international business machines MarketScan Medicare Supplemental claims data. Eligible frail patients (per Claims-based Frailty Index score) initiating mirabegron were 1:2 propensity score matched (based on age, sex, and other characteristics) with those initiating antimuscarinics and were followed up to 1 year. All-cause, per-person, per-month costs, health care encounters, persistence (median days to discontinuation assessed using Kaplan-Meier methods) and adherence (≥80% of proportion of days covered at Day 365) were compared., Results: From 2527 patients with incident mirabegron (21%) or antimuscarinic (79%) dispensations, 516 incident mirabegron users (median age: 82 years, 64% female) were matched to 1032 incident antimuscarinic users (median age: 81 years, 62% female). Median cost was higher in mirabegron group ($1581 vs. $1197 per month); this was primarily driven by medication cost. There was no difference in medical encounters. Adherence (39.1% vs. 33.8%) and persistence (103 vs. 90 days) were higher in mirabegron users., Conclusions: Among frail older adults with OAB, mirabegron use was associated with higher costs and potential improvements in treatment-taking behaviors, particularly with respect to treatment adherence, versus those initiating antimuscarinics., (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Aims: There is no clear pathophysiologic evidence determining how long overactive bladder (OAB) medication should be continued. We, therefore, investigated the effect of mirabegron using cessation (CES) or continuation (CON) treatment in an OAB animal model., Methods: Female C57BL/6 mice were divided into four groups (N = 8 each): Sham, OAB, CES, and CON groups. The OAB-like condition was induced by three times weekly intravesical instillations of KCl mixture with hyaluronidase. After the last intravesical instillation for inducing OAB, mirabegron (2 mg/kg/day) was administered in CES and CON groups for 10 and 20 days, respectively. Final experiments were carried out on 20 days from the last intravesical instillation in all groups. After cystometry, mRNA levels of bladder muscarinic, β-adrenergic, and P2X purinergic receptors were measured to investigate bladder efferent and afferent activity. In addition, mRNA levels of CCL2 and CCR2 in L6-S1 dorsal root ganglia (DRG) were measured to assess afferent sensitization. Immunofluorescent staining of CX3CR1, GFAP, and CCR2 in the L6 spinal cord was also conducted to investigate glial activation and central sensitization., Results: OAB mice showed bladder overactivity evidenced by decreased intercontraction interval (3.56 ± 0.51 vs. 5.76 ± 0.95 min in sham mice), increased non-voiding contractions (0.39 ± 0.11 vs. 0.13 ± 0.07/min in sham mice), and inefficient voiding (72.1 ± 8.6% vs. 87.1 ± 9.5% in sham mice). Increased M2, M3, β2, β3, P2X 2 , P2X 3 , P2X 4 , and P2X 7 levels in the bladder and increased CCL2 and CCR2 in DRG indicate bladder efferent and afferent hyperexcitability. In addition, CX3CR1, GFAP, and CCR2 in the L6 spinal cord were upregulated in OAB mice. However, the CON group exhibited reduced β2, β3, P2X 2 , P2X 3 , P2X 4 , and P2X 7 levels in the bladder, reduced CCL2 and CCR2 in DRG, which are markers of afferent hyperexcitability, and reduced immunoreactivities of CX3CR1, GFAP, and CCR2 in the L6 spinal cord, which are markers of the central sensitization. Moreover, the CON group showed better improvements in nonvoiding contractions (0.16 ± 0.09 vs. 0.44 ± 0.17/min) and voiding efficiency (93.9 ± 7.4% vs. 76.5 ± 13.1%) and reductions in bladder β3 receptors and CCL2 of L6-S1 DRG, and immunoreactivities of CX3CR1 and GFAP in the L6 spinal cord compared to the CES group., Conclusions: Continuous mirabegron treatment seems to prevent central sensitization and, thus, might be desirable for long-term disease control of OAB., (© 2022 Wiley Periodicals LLC.)

Aim: To assess real-world treatment profiles, including utilization rate, time to and reasons for discontinuation of combination pharmacotherapy with β 3 -agonists and antimuscarinics for refractory overactive bladder (OAB) through a retrospective chart review., Methods: We retrospectively reviewed the records of OAB patients who received β 3 -agonists or antimuscarinics at our hospital between 2012 and 2020 and analyzed the clinical course of patients who progressed to combination therapy. Data on age, sex, major complaints, OAB symptom score at the initiation of combination therapy, treatment persistence, and reasons for discontinuation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and persistence rate at 12 months., Results: Of the 2163 patients receiving β 3 -agonists or antimuscarinics, only 84 (3.8%) progressed to combination therapy with both drug classes. At therapy initiation, most (98%) of these patients had moderate to severe OAB symptoms. Median treatment duration and 12-month persistence rate for combination therapy were 595 days and 64.0%, respectively. The reasons for discontinuation were insufficient treatment efficacy followed by adverse effects including voiding impairment in nearly 10% of the patients. None of the baseline parameters was independently associated with persistence in the multivariate analysis., Conclusion: While underutilized among OAB patients refractory to monotherapy, combination pharmacotherapy showed a greater persistence rate than published mirabegron or antimuscarinic monotherapy when applied to patients with moderate to severe symptoms. Treatment-emergent voiding impairment is a concern associated with this mode of therapy. A small sample size at a single institution is the limitation of this study., (© 2022 Wiley Periodicals LLC.)

Purpose: A growing literature points to an association between overactive bladder (OAB) medications and dementia. Given differences in side effects for extended-release (ER) and immediate-release (IR) anticholinergic formulations and beta-3 agonists, we examined prescription utilization patterns in a national dataset of older adults from 2014 to 2018., Methods: We performed a retrospective study using the Medicare Part D Drug Spending Dashboard, a publicly available database that includes data from outpatient pharmacy claims from 2014 to 2018 in the United States. We identified total claims and total spending on common OAB medications, and further assessed trends by anticholinergic burden by medication, and immediate and ER formulations., Results: There were 54.1 million claims for OAB medications, accounting for $10.1 billion (2018 United States dollars) in spending from 2014 to 2018. When considering beta-agonist, mirabegron accounted for 13.1% of total claims and 29.0% of total spending. Mirabegron accounted for a greater proportion of OAB medication claims and spending during the 5 years from 5.7% to 20.1% and 11.3% to 44%, respectively. IR anticholinergics accounted for fewer total claims over this period, from 58.5% to 42.6%. ER formulations increased in proportion of all OAB medication total claims from 35.8% to 37.5% from 2014 to 2016, and decreased to 37.3% by 2018., Conclusion: OAB medications and expenditures increased from 2014 to 2018. Mirabegron accounted for higher proportions and IR-formulations for decreased proportions of each from 2014 to 2018. The impact on clinical outcomes is a key area for future investigation considering our findings., (© 2022 Wiley Periodicals LLC.)

Purpose: We aimed to explore the pathways followed by patients with overactive bladder (OAB) from referral to the urologist to final treatment., Methods: This was a single-center, retrospective cohort study of female patients diagnosed with OAB in a large Dutch nonacademic teaching hospital. The number, sequence, and duration of treatment steps offered were analyzed, and the effectiveness, reasons for discontinuation, and possible case-mix variables influencing OAB treatment were studied., Results: In total, 120 patients were enrolled and required a median of 2 steps (range, 1-6) of treatment over a median total duration of 28 weeks (range, 5-256). Treatment typically started with drug therapy, including antimuscarinics (38%; 95% CI, 30%-47%), antimuscarinics plus pelvic floor muscle therapy (21%; 95% CI, 15%-29%), or mirabegron (11%; 95% CI, 6%-18%). However, 52% of patients required further treatment, with botulinum toxin A (BoNT-A) injections being most effective (67%; 95% CI, 42%-85%), followed by antimuscarinics plus percutaneous tibial nerve stimulation (50%; 95% CI, 25%-75%), and antimuscarinics plus pelvic floor muscle therapy (36%; 95% CI, 21%-54%). Other therapies showed lower effectiveness. Common reasons for discontinuation were insufficient response and side effects. Overall, 22 patients were lost to follow-up., Conclusion: Most patients try at least two treatments before they experience satisfactory symptom relief, with treatment evaluations requiring time because therapeutic onsets differ by patient and treatment. Our data can help to manage expectations among urologists and patients when seeking treatment for OAB., (© 2021 Wiley Periodicals LLC.)

Aims: To descriptively evaluate treatment persistence among adults who received mirabegron or antimuscarinics in South Korea., Methods: This study involved a retrospective analysis of the Health Insurance Review and Assessment (HIRA) database. Patients (≥18 years) who had a new prescription for an overactive bladder (OAB) target medication (mirabegron/antimuscarinic) within an 8-month index period (July 1, 2015-February 29, 2016) were included. The date when the target (index) medication was dispensed was the index date. The 6-month period before the index date was used to assess patient eligibility. A 12-month post-index period was used to assess medication persistence, which was defined as the time to discontinuation. Overall data were analyzed and the results were also stratified by age group (≤65, >65 years), sex, or prior OAB medication experience. Persistence rates were calculated after the 1st, 3rd, 6th, 9th, and 12th months., Results: A data set of 52 722 cases was obtained (mirabegron: 11 424, antimuscarinics: 41 298). The mean age was 60.9 ± 16.1 years and the majority of the patients were female (30 862 [58.5%] patients). Median persistence was longer with mirabegron (51 days) versus antimuscarinics (25 days). The persistence rate with mirabegron was higher throughout the study compared with all the antimuscarinics (12-month data: 13.5% and 4.9%, respectively). Longer treatment persistence was noted in older, male, and treatment-experienced patients., Conclusion: The results from the HIRA database showed that persistence was longer with mirabegron than with antimuscarinics in South Korea. This finding may help inform clinical decision-making within the South Korean healthcare system., (© 2021 Wiley Periodicals LLC.)

Objective: To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI)., Methods: This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline., Results: A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 ml to 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 h to 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H 2 O to 41 cm H 2 O (p = .005) at 6 weeks. Only two patients reported new onset dry mouth. No major adverse events were noted and none discontinued treatment., Conclusion: Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI., (© 2021 Wiley Periodicals LLC.)

Aims: This study aimed to investigate the efficacy and safety of mirabegron for Parkinsonism patients with overactive bladder (OAB) symptoms in a randomized, placebo-controlled, multicenter study., Materials and Methods: Inclusion criteria are Parkinsonism with OAB symptoms for 4 weeks or more, OAB symptom score (OABSS) questionnaire scores greater than 2, and OABSS urgency question scores greater than 1. After a 2-week wash-out period, the patients were randomized into placebo and mirabegron groups at visit 2. Visit 3 was performed after 4 weeks of medication. Mirabegron was prescribed to the two groups for the rest of the study period at visit 4., Result: The mean age was 68.1 ± 8.1 years and 72 males and 64 females were included. A total of 136 patients were screened, 117 patients were randomized, and 25 patients dropped out. The OABSS scores were significantly different between the two groups at Weeks 4 and 8. The OABSS scores became the same in the two groups at Week 12 (visit 5). The postvoid residual urine volume showed a mild increase to 64 ml in the mirabegron group compared to the placebo group at visit 4. Adverse events occurred in 27 patients (23.1%). The degree was mild in 26 cases (78.8%), moderate in five (15.2%), and severe in two (6.1%). Only 13 cases (39.4%) showed medication-related adverse events. Acute urinary retention occurred in a single case. The treatment satisfaction questionnaires showed no significant differences between the two groups., Conclusion: Mirabegron was effective in treating OAB symptoms in patients with Parkinsonism with acceptable adverse events., (© 2020 Wiley Periodicals LLC.)

Aim: To assess real-world treatment profiles, including the time to and reasons for discontinuation or drug switching, treatment reinitiation, and postdiscontinuation follow-up in patients receiving antimuscarinics or ß3-agonists for overactive bladder (OAB) through a retrospective chart review., Methods: We retrospectively reviewed medical charts of 777 patients, aged ≥18 years, who underwent antimuscarinic or ß3-agonist therapy at our hospital. Data on patient's age, sex, chief complaint, and OAB symptom score at therapy initiation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and the persistence rate at 12 months., Results: Older patients, male patients, and those with more severe urgency symptoms were more likely to show treatment persistence with OAB medications. Treatment persistence with mirabegron was significantly longer than that with antimuscarinics when administered as either the first- or second-line medication. Multivariate analyses showed that urgency severity and use of mirabegron were independently associated with better persistence (p = .026 and p = .018, respectively). Out of 583 patients who discontinued medication, 344 continued with the visit schedule, and the reinitiation rate of the OAB medication was 19% at a median follow-up of 24 months., Conclusion: Although the persistence rates for OAB medications improved with the introduction of mirabegron, most patients still discontinued the medication therapy within 1 year. The treatment strategies for patients with mild symptoms and those who are resistant to medication can still be improved. Tailored individualized treatments that avoid excessive reliance on pharmacotherapy would be key to further improve treatment outcomes in OAB patients., (© 2020 Wiley Periodicals LLC.)

Aim: We investigated the satisfaction and efficacy of mirabegron in patients with overactive bladder (OAB) symptoms who were unsatisfied with previous antimuscarinic treatment., Methods: This was a 12-week, open-label study of adults with OAB who had been treated with antimuscarinics within 2 years of screening and expressed dissatisfaction over poor efficacy or adverse events of antimuscarinics. All enrolled patients have received mirabegron 50 mg once daily for 12 weeks. The primary outcome was the percentage of patients reporting treatment satisfaction questions (TSQ) at week 12 ("very satisfied" or "somewhat satisfied"). Patients completed voiding diaries, Overactive Bladder Questionnaire short form (OAB-q-SF), Overactive Bladder Symptom Score (OABSS), and the global response assessment (GRA) at baseline, Week 4, and Week 12. At 12-weeks, patients were assessed for willingness to continue treatment., Results: The response rate of treatment satisfaction at 12 weeks was 69.3% (275/397) (95% confidence interval 64.7-73.8). Significant improvements from baseline to weeks 4 and 12 were observed in the frequency, urgency due to urinary incontinence, and urgency episodes per 24 h (all p < .0001). Both OAB-q-SF and OABSS were significantly improved compared to baseline. At 4 and 12 weeks, 27.5% and 41.8% of patients, respectively, responded to the GRA as being moderately or markedly improved. At 12 weeks, 80.8% of patients were willing to continue mirabegron., Conclusions: Mirabegron improved the rates of treatment satisfaction and symptoms in patients with OAB who were unsatisfied with prior antimuscarinic treatment., (© 2020 Wiley Periodicals LLC.)

Introduction: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA)., Methods: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy., Results: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802])., Conclusions: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial., (© 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Aim: To evaluate efficacy and safety of combination of tadalafil + mirabegron for overactive bladder/benign prostatic hyperplasia (OAB/BPH)., Methods: Male patients with lower urinary tract symptoms (50 to 89 years), with remaining OAB symptoms even after administering tadalafil for more than 8 weeks were randomly assigned to either tadalafil monotherapy group (5 mg/day) or tadalafil/mirabegron combination therapy group (5 mg/50 mg/day). The primary endpoint was change from baseline in total OAB symptom score (OABSS) at week 12. The secondary endpoints were changes in International Prostate Symptom Score (IPSS), NIH-chronic prostatitis symptom index (NIH-CPSI), and micturition chart parameters at weeks 4 and 12., Results: A total of 176 patients were randomized to either monotherapy (87 patients) or combination therapy (89 patients). The baseline characteristics of patients in the two groups were similar. The total OABSS (95% confidence interval) of combination therapy was significantly decreased by 1.78 (1.05-2.50) points compared with that of monotherapy (P < .001). Changes from baseline in OABSS nighttime voiding score, urgency score, urgency incontinence score, IPSS storage subscores, NIH-CPSI total score, and numbers of voids, nighttime-voids, and urgency episodes/day in micturition chart were significantly reduced in combination therapy (all P < .001). Patient-reported outcome was significantly more satisfactory in combination therapy than in monotherapy (P < .001). One moderate adverse event (pain in hip joint) with hardly presumed causal relationship with therapy and seven mild adverse events were noted in monotherapy and combination therapy group, respectively., Conclusions: The effect of tadalafil/mirabegron combination therapy on relieving OAB symptoms appeared to be greater than that of tadalafil monotherapy and can be safely used., (© 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.)

Aims: To compare the efficacy of fesoterodine or mirabegron add-on therapy for persistent overactive bladder (OAB) symptoms despite silodosin monotherapy in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, in both subjective and objective aspects., Methods: A total of 120 patients with persistent OAB symptoms despite silodosin monotherapy were randomized to receive add-on therapy with fesoterodine (4 mg/day) or mirabegron (50 mg/day) for 12 weeks. At week 12, changes from baseline in patients' subjective symptoms and voiding/storage functions, as assessed using the International Prostate Symptom Score (IPSS), OAB symptom score (OABSS), and urodynamic studies, were compared between the groups., Results: The final analysis included 50 and 52 patients in the fesoterodine and mirabegron groups, respectively. Although the IPSS and OABSS significantly improved in both groups, the fesoterodine (vs mirabegron) group showed significantly greater improvements in the OABSS-total (-2.8 vs -1.5, P = 0.004), IPSS-QOL (-1.5 vs -1.1, P = 0.04), and OABSS-urgency score (-1.5 vs -0.9, P = 0.008) at 12 weeks. Regarding storage functions, although both groups showed significant improvements, the fesoterodine group demonstrated greater improvements in the detrusor overactivity alleviation rate (52.6% vs 28.9%, P = 0.03). Voiding functions did not deteriorate in either group at 12 weeks; no significant inter-group differences were observed. Post-void residual urine significantly increased by 16 mL only in the fesoterodine group., Conclusion: Add-on therapy of fesoterodine to silodosin was more effective than adding mirabegron to silodosin for improving OAB symptoms and storage functions, without deteriorating voiding symptoms or functions., (© 2019 Wiley Periodicals, Inc.)

Aims: SYNERGY II was a 12-month phase III trial in patients with overactive bladder (OAB) symptoms that investigated the safety and efficacy of the combination of mirabegron and solifenacin in comparison with each monotherapy. This analysis evaluated the trial findings using four age subgroups (<65, ≥65, <75, and ≥75 years)., Methods: Eligible patients were ≥18 years with symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for ≥3 months. Patients were randomized to receive once-daily solifenacin succinate and mirabegron (5 mg/50 mg; combination), solifenacin succinate, or mirabegron (4:1:1). Safety evaluations: treatment-emergent adverse events (TEAEs), vital signs, and electrocardiogram, post-void residual volume, and laboratory assessments. Primary efficacy variables: change from baseline to end of treatment in number of incontinence episodes/24 h and micturitions/24 h., Results: Of 1794 patients (full analysis set), 614 (34.2%) and 168 (9.4%) were ≥65 and ≥75 years old, respectively. Overall, 856 (47.2%) patients experienced ≥1 TEAE. Higher TEAE incidences were typically observed for the combination versus both monotherapies (eg, constipation) and in the older versus younger age groups (eg, urinary tract infection). Increases in mean pulse rate from baseline of >1 bpm were noted in the combination and mirabegron younger age groups only. No clinically significant findings were observed in the other safety parameters. The efficacy variables improved with all treatments and the greatest improvements were typically observed with combination therapy., Conclusions: Mirabegron and solifenacin combination therapy was a well-tolerated and effective treatment for patients with OAB symptoms irrespective of their age., (© 2019 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.)

Aims: To evaluate the efficacy and safety of mirabegron in males with overactive bladder (OAB) symptoms., Methods: In total, 464 males with OAB symptoms were enrolled from 14 institutes and were sorted into either the mirabegron 50 mg (n = 310) or placebo (n = 154) groups. The change in (i) the mean number of 24-h micturition episodes; (ii) OAB Symptom Scale (OABSS); and (iii) International Prostate Symptom Score (IPSS) from baseline to 12 weeks of treatment were compared between the two groups. Safety assessments included treatment-emergent adverse events, blood pressure, pulse rate, postvoid residual volume, and maximum urinary flow rate. After 12 weeks, the study was extended for 14 additional weeks by administering mirabegron 50 mg to both groups., Results: The reduction in the mean number of 24-h micturition episodes from baseline to 12 weeks of treatment was similar between the two groups. However, significantly greater changes from baseline to 12 weeks were observed in total OABSS, OABSS urgency incontinence score (Q4), IPSS storage subscore (Q2 + Q4 + Q7), and IPSS urgency score (Q4) in the mirabegron group (P = 0.01 for all). According to the extended study, the changes of all efficacy variables from baseline to 26 weeks were similar between both groups. The safety assessment results were also similar between the two groups at 12 and 26 weeks., Conclusion: A daily 50 mg dose of mirabegron for 12 weeks reduced OAB symptoms in men, and no significant adverse events compared to the placebo group were noted., (© 2018 Wiley Periodicals, Inc.)

Aim: We conducted a meta-analysis to evaluate the safety and efficacy of mirabegron (50 mg) and solifenacin (5 mg) monotherapy for overactive bladder (OAB) during a 12-week cycle., Methods: Randomized controlled trials (RCTs) of mirabegron and solifenacin for OAB were searched systematically by using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of retrieved studies were also perused., Results: Five RCTs which compared solifenacin with mirabegron were studied. Mirabegron achieved the same effect as solifenacin in treating OAB. The mean number of incontinence episodes per 24 h (P = 0.20), mean number of micturitions per 24 h (P = 0.11), mean number of urgency episodes per 24 h (P = 0.23), and mean volume voided per micturition (P = 0.05) suggested that mirabegron and solifenacin had no significant differences in terms of OAB treatment. With regard to drug-related treatment-emergent adverse events (DR-TEAEs) and dry mouth, mirabegron showed better tolerance than solifenacin. Post-voiding residual volume showed a distinct difference in the two groups. Hypertension and tachycardia did not show a significant difference between the two groups, but the pulse rate did., Conclusion: The therapeutic effect of mirabegron is similar to that of solifenacin, and mirabegron does not increase the risk of adverse events (AEs)., (© 2018 Wiley Periodicals, Inc.)

Aims: To determine the effectiveness of mirabegron in patients with neurogenic lower urinary tract dysfunction., Methods: Randomized, double-blind, placebo-controlled study. Canadian patients with spinal cord injury (SCI) or multiple sclerosis (MS) with urinary symptoms and incontinence were recruited. Patients were randomized to mirabegron 25 mg (or an identical placebo) for 2 weeks at which point a dose escalation to mirabegron 50 mg (or an identical placebo) was maintained for 8 weeks. Urodynamics were performed before and after treatment. The primary outcome measure was maximum cystometric capacity (MCC). Intention to treat analysis and ANCOVA models (with adjustment for baseline values) were used and marginal means (MM) are reported; P-value <0.05 was considered significant., Results: Sixteen (9 SCI and 7 MS) patients were randomized to mirabegron and 16 (10 SCI and 6 MS) to placebo. At study completion, there was no significant difference in MCC between mirabegron and placebo (MM 305 vs 369 mL, P = 0.20). There was no significant difference in volume at first neurogenic detrusor overactivity (NDO, MM 167 vs 137 mL, P = 0.14) and peak pressure of NDO (MM 69 vs 82 cmH 2 O, P = 0.25). There was no significant difference in pad weights or voiding diary parameters. There was a significantly lower symptom burden among those treated with mirabegron (total neurogenic bladder symptom score MM 29 vs 34, P = 0.047)., Conclusions: Among patients with SCI or MS, we demonstrated non-significant trends towards improvement in some urodynamic parameters with mirabegron 50 mg compared to placebo, and a significantly lower neurogenic bladder symptom burden., (© 2018 Wiley Periodicals, Inc.)

Aims: To assess the efficacy and safety of mirabegron in the treatment of neurogenic detrusor overactivity., Methods: This prospective, multicenter, randomized, double-blind, placebo-controlled study was conducted in three tertiary centers, and included 78 patients suffering from spinal cord injury or multiple sclerosis. Patients were randomized for Mirabegron 50 mg (Group A) or placebo (Group B). Urodynamic parameters, the 24 h pad-weight test, and patient-reported outcomes were assessed. Safety assessments included monitoring the incidence and severity of adverse events. Changes in time and differences between groups were assessed with nonparametric Kruskal-Wallis one-way analysis of variance; P ≤ 0.05 was considered statistically significant., Results: In total, 66 patients were eligible for inclusion in the final analysis. There was a significant increase of volume at the first detrusor contraction (P = 0.00047) and an improvement in bladder compliance (P = 0.0041) in the mirabegron group compared with the placebo-treated group, whereas the increase in cystometric capacity did not reach statistical significance (P = 0.061). There was a clear tendency to reduced urine leakage (P = 0.056) in Group A. There were significant changes in all the patient-reported outcomes, favoring the mirabegron group. The incidence of drug-related adverse events was 3.13%., Conclusions: Mirabegron (50 mg) improved both urodynamic variables and patient-reported outcomes in patients with NDO. The treatment was tolerated well., (© 2018 Wiley Periodicals, Inc.)

Aims: To examine early trends in the use of overactive bladder (OAB) agents across Canada, with a focus on initial uptake and reimbursement of two newer agents: fesoterodine, an anticholinergic, and mirabegron, a therapeutically novel beta-3 agonist., Methods: We conducted a population-based cross-sectional study of outpatient prescriptions for long-acting oral OAB agents dispensed to individuals in Canada between May 2010 and April 2015 to examine the differences in the uptake of the newer agents and their reimbursement through cash, private, and public payers., Results: The national dispensing rate of OAB agents increased by 60% from May 2010 to April 2015 (from 924 to 1475 units per 10 000). We observed an increase in the dispensing rate of fesoterodine, solifenacin, and mirabegron, but a decrease in that of tolterodine and oxybutynin. Mirabegron was adopted rapidly after Health Canada approval, growing to a rate of 191 units per 10 000 by study completion, with its uptake being primarily funded through private payers (72.2%). Conversely, fesoterodine's uptake was minimal (8.3 units per 10 000) prior to its listing on public plans. This increased to 185 units per 10 000 by study completion, with the majority (65%) paid for by public insurers., Conclusions: The differences in the uptake and reimbursement of two new OAB agents emphasize the impact of therapeutically novel agents on the prescription rates of older OAB agents with significant adverse effects. Further studies are needed to explain changes in the dispensing rates as more provinces list the newer drugs on their formulary., (© 2018 Wiley Periodicals, Inc.)

Aims: To evaluate patient-reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial., Methods: Following a 4-week placebo run-in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2-week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB-q Symptom Bother score, health-related quality of life (HRQOL) Total score, treatment satisfaction-visual analogue scale (TS-VAS), and patient perception of bladder condition (PPBC) questionnaires., Results: Overall, 3527 patients were randomized into the study, with 3494 receiving double-blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB-q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups., Conclusions: PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB-q Symptom Bother score, HRQOL Total score, and PPBC., (© 2017 Wiley Periodicals, Inc.)

Aims: To understand differences in patient reported outcomes (PRO) between patients initiating mirabegron or an antimuscarinic using a validated PRO instrument, OAB-Satisfaction (OAB-S)., Methods: This prospective observational study used real-time prescription claims from Humana to identify Medicare patients initiating mirabegron or an antimuscarinic to participate in a series of three phone surveys over ninety days., Results: A total of 1897 mirabegron and 2444 randomly selected antimuscarinic initiators were identified; 174 mirabegron and 193 antimuscarinic initiators completed all three surveys. Among responders, mirabegron initiators were slightly older (76 vs 75 years, P = 0.032), included more males (32% vs 23%, P = 0.044), more likely to have prior OAB treatment (21% vs 13%, P = 0.048), and had greater medication burden (number of unique medications: 10.0 vs 8.7, P = 0.014). There were no between-group differences at any time or on any OAB-S scale. There were significant within-group differences at follow-up compared to baseline for OAB-S scales: "impact on daily living," with improvement over the 90-day survey period for both mirabegron (P = 0.008) and antimuscarinic (P < 0.001); "interruption of day-to-day life," with improvement for both mirabegron (P < 0.001) and antimuscarinic (P < 0.001); and improvement in "OAB control" for mirabegron (P < 0.001) and antimuscarinic (P < 0.001)., Conclusions: Mirabegron initiators tended to be older, had a greater number of unique medications and previously tried prescriptions to treat OAB; nonetheless, mirabegron, and antimuscarinic initiators reported similar trends in improvement in PROs over the first 90 days of treatment. Significant improvement in daily impact of OAB was observed after treatment initiation; however, no significant differences between groups were observed., (© 2017 Wiley Periodicals, Inc.)

Background: Overactive bladder syndrome (OAB) is a chronic and prevalent condition which has a negative impact on Quality of Life. The National Institute of Clinical Excellence issued two documents which give slightly varying algorithms of pharmacotherapy for OAB, offering mirabegron as a possible treatment in certain circumstances. In the absence of trials involving a direct comparison of therapies, an indirect comparison can provide useful information on the difference in treatment effects between competing interventions., Objective: To compare effectiveness of available medical therapies for OAB using Bucher indirect treatment comparison (ITC) model., Methods: A systematic literature search identified randomised controlled trials (RCT) assessing effectiveness of drugs for OAB versus placebo. Then indirect comparisons of the treatments effects were made, preserving the randomisation of the originally assigned patient groups, using Bucher method., Main Results: 25 RCTs met inclusion criteria. In keeping with ITC method validity, four assessments were undertaken of mirabegron against anticholinergics, which were number of incontinence episodes, micturition episodes, urgency episodes in 24 h and volume of micturition. This indirect treatment analysis suggests that mirabegron is as effective as anticholinergics in managing of OAB, except for solifenacin which appears to be superior., Conclusions: These findings suggest that work looking into treatment choice should be individualized to patient characteristics rather than fitting patients to a treatment. Further work is required to identify what patient characteristics may be crucial and indicate that studies exploring the most effective sequence of managing treatment naïve patients and those with refractory disease., (© 2017 Wiley Periodicals, Inc.)

Aims: To evaluate the effects of the beta-3 adrenoceptor agonist, mirabegron in a mouse model of detrusor overactivity induced by obesity., Methods: C57BL/6 male mice were fed with standard chow or high-fat diet for 12 weeks. Lean and obese mice were treated orally with mirabegron (10 mg/kg/day) from the last 2 weeks of diet. Cystometric evaluations, functional assays, protein expression for phosphodiesterase type 4 (PDE4), and cyclic adenosine monophosphate (cAMP) measurement were carried out., Results: In obese mice the body weight, epididymal fat mass, fasting glucose, and low-density lipoprotein (LDL) levels were higher (P < 0.001) than in the lean mice. A reduction of 34% and 54% and an increase of 35% in the epididimal fat, LDL, and HDL levels (P < 0.05), respectively, were observed in the obese group treated with mirabegron, whereas no changes were seen in the lipid profile from lean mice. Obese group showed irregular micturition pattern, characterized by significant increases in frequency and non-void contractions. Carbachol, potassium chloride, and electrical-field stimulation induced detrusor smooth muscle (DSM) contractions, which were greater in bladders from obese mice than from lean mice. Two-week treatment with mirabegron restored all the contractile response alterations in the DSM. Basal intracellular levels of cAMP were reduced (68%), whereas PDE4 protein expression was increased (54%) in bladder from obese mice. Mirabegron restored the cAMP levels in obese bladder, without changing the PDE4 expression., Conclusion: Mirabegron was able to completely restore the urinary alterations seen in the bladder from obese mice., (© 2016 Wiley Periodicals, Inc.)

Aims: To investigate the effects of combined therapy with an anticholinergic agent and a β3-adrenoceptor agonist on bladder dysfunction and proliferation-related molecule expression in rats with spinal cord injury (SCI)., Methods: The spinal cord was transected at the level of T8-9 in female Sprague-Dawley rats, which were divided into four groups; A: Vehicle, B: 10 mg/kg/day of oxybutynin, C: 10 mg/kg/day of mirabegron, and D: combined administration of oxybutynin and mirabegron. Drugs were administered by oral gavage from 2 to 4 weeks after spinal cord transection. We evaluated urodynamic parameters and bladder tissue remodeling factors., Results: Non-voiding contractions (NVCs) during the storage phase of cystometrograms tended to be decreased in all three treated groups with a significant reduction in group D versus A. Bladder compliance was improved, and intercontraction intervals, voided volume and bladder capacity were increased in group D. In all three treated groups (B-D), the expression of HIF1-α and TGF-β1 was decreased compared to group A. The expression of collagen-III and bFGF was decreased in groups B and D. The total bladder elastin level was increased in group D., Conclusions: The combination therapy of an anticholinergic agent and a β3-adrenoceptor agonist elevated the bladder elastin level, reduced NVCs, and increased bladder compliance more effectively than the monotherapy in SCI rats. Thus, the combination therapy could be effective for the treatment of neurogenic bladder dysfunction including bladder remodeling. Neurourol. Urodynam. 36:1039-1045, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Aims: We aimed to compare the efficacy and safety of mirabegron, a β3-adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients., Methods: We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged ≥50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50 mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2 mg per day) for 8 weeks. This order of drug administration was reversed in Group B., Results: A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24 hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not., Conclusions: Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 36:1097-1103, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Aims: To evaluate persistence rates of patients receiving mirabegron therapy for overactive bladder (OAB) within our institution over a 6 month period, identify determinants of early discontinuation of therapy, and assess overall patient satisfaction with treatment., Methods: Hospital prescription data were analyzed in order to identify all patients who had been prescribed mirabegron in our institution. Case notes were retrospectively reviewed to obtain demographic data, previous treatments for OAB, reasons for discontinuation of previous treatments, and duration of treatment with mirabegron. Overall satisfaction with treatment was assessed using the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q)., Results: One hundred and ninety-seven patients were prescribed mirabegron. Of these, 81% previously discontinued anticholinergic therapy, 14% had previously received intravesical botulinum toxin A therapy, and 19% were prescribed mirabegron first-line. At 3 months 69% persisted with treatment which fell to 48% by 6 months. The commonest reason for discontinuation was lack of efficacy, followed by adverse effects. Overall 32% of patients preferred mirabegron over previous treatments and only 39% were satisfied with mirabegron therapy., Conclusion: Persistence rates with mirabegron in this group of patients for OAB are satisfactory. The commonest reasons for discontinuation are unmet treatment expectations and adverse effects. We had very few treatment-naïve patients and so further studies are required to assess mirabegron persistence rates with longer-term follow up, as first-line treatment and in different groups of OAB severity. Neurourol. Neurourol. Urodynam. 36:404-408, 2017. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Aims: To assess patient-reported outcomes (PROs) in patients with overactive bladder (OAB) receiving the novel β 3 -adrenoceptor agonist mirabegron., Methods: Data from a randomised, double-blind, controlled phase III trial in 1,987 patients aged ≥18 years with OAB symptoms for ≥3 months were analysed. Patients received placebo, mirabegron 50 or 100 mg/day, or tolterodine extended release (ER) 4 mg orally once daily for 12 weeks after a 2-week placebo run-in. Prespecified analysis of PROs (changes in OAB Questionnaire [OAB-q], Patient Perception of Bladder Condition [PPBC], and Work Productivity and Activity Impairment: Specific Health Problem [WPAI-SHP] instrument) in patients treated with mirabegron 50 mg/day, tolterodine ER 4 mg/day or placebo is reported. Post-hoc analyses of OAB-q, PPBC and the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) in patients who were incontinent at baseline are also reported., Results: Significant improvements over placebo in OAB-q coping and concern from baseline to final visit were observed with mirabegron 50 mg/day. No significant improvements in these parameters were observed with tolterodine ER 4 mg/day. Mirabegron 50 mg/day significantly increased the proportion of patients showing a PPBC improvement over placebo. Mirabegron 50 mg/day also produced greater improvements in WPAI-SHP presenteeism and greater reductions in absenteeism and overall work impairment than placebo or tolterodine ER 4 mg/day. The impact of mirabegron 50 mg/day treatment on PROs in the incontinent population appears to be greater than that in the overall OAB population., Conclusions: At the approved dose of 50 mg/day, mirabegron significantly improves OAB patients' perception of disease and quality of life, independent of whether they are incontinent at baseline. Neurourol. Urodynam. 35:987-994, 2016. © 2015 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc., (© 2015 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.)

Aims: To provide a clinical view and interpretation on the methods for analysis of incontinence in patients with overactive bladder., Methods: Results are analyzed using the total number of incontinence episodes in a 3-day diary period, using fixed and random effect Poisson regression models to calculate ratio of event rates and 95% confidence interval (CI) together with P-values and are compared with the analysis of the mean number of incontinence episodes/24 hr using analysis of covariance models to calculate P-values and 95% CI for the difference between treatments., Results: Using random effects Poisson regression models demonstrated that the number of incontinence episodes was reduced by 26% more with mirabegron 50 mg than with placebo. For solifenacin 5 and 10 mg, treatment resulted in a 43% (41%) greater decrease in the number of incontinence episodes compared with placebo., Conclusion: Instead of providing a fixed number of incontinence episodes/24 hr that reflects the mean effect, the estimate using Poisson methodology provides an efficacy estimate that can be interpreted in the context of, and relative to, the patient's baseline (severity). Using the total number of incontinence episodes in the diary period, and expressing this as percent decrease in the number of episodes, may be easier to interpret; for example, because this results in a relative measure of effect that provides an alternative understanding of a patient's improvement at end of treatment compared with the comparator arm. Also, it is based on statistical methods that are more suitable for the analysis of count data. Neurourol. Urodynam. 35:728-732, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Aims: To assess the efficacy and safety of mirabegron 50 mg once daily compared with placebo and the active control, tolterodine extended-release (ER) 4 mg once daily, in patients with symptoms of overactive bladder (OAB) in Taiwan, Korea, China, and India., Methods: A 12-week multinational, randomized, double-blind, parallel-group placebo- and active-controlled trial. The primary efficacy endpoint was change from baseline to final visit in mean number of micturitions/24 hr. Secondary endpoints were: mean number of urgency episodes, incontinence episodes and urge incontinence episodes/24 hr, mean number of nocturia episodes per night, mean volume voided per micturition, and quality-of-life (QoL) scores as assessed by the King's Health Questionnaire (KHQ)., Results: Of 1,126 patients who were randomized to receive double-blind study drug, 921 patients (300, 311, and 310 in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively) completed the treatment period. Demographic characteristics were similar across treatment groups. A statistically significant improvement versus placebo in mean number of micturitions/24 hr was seen with mirabegron 50 mg at all timepoints (P < 0.05) as well as final visit (-0.57 with 95% confidence intervals [CIs] of [-1.04, -0.09], P = 0.019). There was no significant difference between treatment groups in improvement from baseline to final visit in any of the secondary outcome measures except volume voided per micturition. The overall incidence of drug-related adverse events was 17.2%, 15.8%, and 21.3%, in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively., Conclusions: Mirabegron 50 mg once daily for 12 weeks was superior to placebo in reducing the frequency of micturitions in patients with symptoms of OAB in Taiwan, Korea, China, and India., (© 2014 Wiley Periodicals, Inc.)

Aims: Mirabegron, the first β3 -adrenoceptor agonist to enter clinical practice, has a different mechanism of action from antimuscarinic agents. This review presents data on the efficacy, safety, and tolerability of mirabegron in studies conducted to date., Methods: All clinical data on mirabegron that are currently in the public domain are included, including some in-press manuscripts., Results: In Phase III clinical trials in patients with overactive bladder (OAB), mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating the symptoms of OAB, including micturition frequency, urgency incontinence, and urgency. Significant improvements in micturition frequency, urgency incontinence, and mean volume voided/micturition were seen as early as the first assessment (week 4) for mirabegron 50 and 100 mg, and were maintained throughout treatment. Responder analyses showed a significant improvement with mirabegron 50 and 100 mg in terms of dry rates, ≥50% reduction in mean number of incontinence episodes/24 hr, and the proportion of patients with ≤8 micturitions/24 hr at final visit. The benefit of mirabegron 50 and 100 mg was also evident in patients ≥65 years of age, and in both treatment-naïve patients and those who previously discontinued antimuscarinic therapy. These data therefore demonstrate a clinically meaningful benefit with mirabegron in the objective endpoints of OAB. Assessment of measures of health-related quality of life and treatment satisfaction showed that patients perceived treatment with mirabegron as meaningful. In OAB clinical trials of up to 12 months mirabegron appeared to be well tolerated. The most common adverse events (AEs) observed with mirabegron in clinical trials of up to 12 months were hypertension, nasopharyngitis, and urinary tract infection. The incidence of dry mouth was similar to placebo, and was between three and fivefold less than for tolterodine extended release 4 mg. Since dry mouth is the most bothersome AE associated with antimuscarinic drugs and often a reason for treatment discontinuation, mirabegron may be a valuable treatment option for these patients., Conclusions: In Phase III clinical trials, mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating symptoms of OAB and, at doses of 50 and 100 mg, demonstrated significant improvements versus placebo on key secondary endpoints, as early as the first assessment (week 4), and these were maintained throughout treatment. In OAB clinical trials of up to 12 months, mirabegron appeared to be well tolerated., (© 2013 Wiley Periodicals, Inc.)

Aims: To evaluate the potential of mirabegron, a selective β3-adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms., Methods: A multicenter, randomized, double-blind, double-dummy, parallel group, placebo and active-controlled, Phase 2, proof-of-concept study was conducted. Eligible patients (n = 314) were enrolled into a single-blind, 2-week placebo run-in period followed by a randomized, double-blind, placebo-controlled treatment period. Patients received mirabegron 100 or 150 mg twice-daily (BID), placebo or tolterodine 4 mg extended release (ER) once-daily for 4 weeks. Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24 hr. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes per 24 hr; severity of urgency; nocturia, and quality of life measures. Safety parameters included adverse events, laboratory tests, electrocardiogram parameters and post-void residual volume., Results: Mirabegron 100 and 150 mg BID resulted in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency (2.2 micturitions/24 hr vs. 1.2 micturitions/24 hr for both doses, adjusted P ≤ 0.01 for both comparisons). Mirabegron had a statistically significant effect versus placebo for most secondary endpoints, including quality of life variables. Despite a small increase in pulse rate, mirabegron demonstrated good safety and tolerability., Conclusions: Mirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years., (© 2013 Wiley Periodicals, Inc.)