mirabegron and Urinary-Incontinence--Urge

To summarize recent data on the medical treatment of men with incontinence due to overactive bladder or to stress urinary incontinence published in peer-reviewed journals.. Previous randomized controlled trials have shown that both antimuscarinic drugs and α1-adrenoceptor blockers can be useful for treatment of male lower urinary tract symptoms, including the overactive bladder syndrome, and that combination of the two principles may offer additional benefits over monotherapy with either agent. This has been further confirmed in several recent studies. There seems to be an associated increase in postvoid residual urine volume by the combinations, but not a significantly increased risk of retention. The efficacy of other combinations, for example, α1-adrenoceptor blocker and 5α-reductase inhibitor, has also been further documented. Recent evidence supports the use of mirabegron, alone or in combination with solifenacin, as a treatment alternative of male overactive bladder syndrome. Monotherapy with phosphodiesterase 5 inhibitors seems to be as effective as α1-adrenoceptor blockers in male lower urinary tract symptoms. Only a few recent studies have been performed on the pharmacological treatment of male stress urinary incontinence, confirming that duloxetine had a modest positive effect in men with postprostatectomy incontinence.. For treatment of storage symptoms in men with lower urinary tract symptoms, combinations of antimuscarinics and α1-adrenoceptor blockers have produced the most promising results. Duloxetine exerts only modest relief of male stress urinary incontinence, but may be recommended in some patients.

Topics: 5-alpha Reductase Inhibitors; Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Muscarinic Antagonists; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urinary Incontinence, Urge; Urological Agents

Overactive bladder (OAB) is defined by its hallmark symptom, urgency. It can be associated with urge urinary incontinence (UUI), and dramatically impact the patients' quality of life. Etiologies of OAB are numerous, and under this common wording, virtually all the population is covered (men as well as women, patients with or without neurogenic disease, and all age categories). OAB and UUI management have been historically based on non-interventional therapies, antimuscarinics, and surgery. In the last decade, innovations in the treatment of this highly prevalent condition have been multiple, and further insights came from various horizons (drug invention, innovative use of existing drugs, new medical devices, tissue engineering, gene and cell therapy). Notably, the use of BoNT and neuromodulation techniques have deeply modified the algorithm of specialized OAB management, delaying surgery indications and offering mini-invasive alternatives to patient refractory to behavioral and medical treatment. Whilst some of these techniques are about to reach maturity, numerous questions remain unsolved about their indications, long term effects, rank in the armamentarium, cost-effectiveness, hypothetical combination or sequential use. The present review depicts the actual wide range of options available for OAB management in adults, focusing on the latest evolutions. When relevant, a distinction was made between genders and OAB subtypes (idiopathic vs neurogenic) regarding treatment outcomes.

Topics: Acetanilides; Botulinum Toxins, Type A; Caffeine; Clinical Trials, Phase III as Topic; Drinking Behavior; Electric Stimulation Therapy; Electrodes, Implanted; Exercise Therapy; Female; Humans; Male; Multicenter Studies as Topic; Muscarinic Antagonists; Neurokinin-1 Receptor Antagonists; Pelvic Floor Disorders; Phosphodiesterase Inhibitors; Randomized Controlled Trials as Topic; Therapies, Investigational; Thiazoles; Urinary Bladder Neck Obstruction; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urologic Surgical Procedures

To investigate safety, tolerability and efficacy of long-term (52 weeks) open-label treatment with mirabegron 50 mg, with an optional dose increase to 100 mg, in patients with overactive bladder (OAB).. Patients received mirabegron 50 mg once daily for 52 weeks. If efficacy was insufficient at week 8, the dose could be increased to 100 mg. Safety was evaluated based on vital signs, adverse events (AEs), laboratory findings, electrocardiogram and post-void residual volume. Treatment efficacy was assessed with a 3-day micturition diary and the King's Health Questionnaire (KHQ).. Two hundred and four patients were enrolled; mirabegron dose was maintained at 50 mg in 153 patients and increased to 100 mg in 50 patients. Mirabegron was well tolerated at both doses. Incidences of AEs and treatment-related AEs were 91.4% and 33.6% in patients on 50 mg, and 100% and 30.0% in patients on 100 mg, respectively. Time course changes in systolic or diastolic blood pressure and pulse rate were not considered clinically significant. At the end of treatment (EOT), patients on 50 mg and 100 mg showed improvement in frequency and urgency. Improvements from baseline to EOT in quality of life scores were observed for all KHQ domains.. There were no safety or tolerability concerns associated with mirabegron 50 mg (with an optional dose increase to 100 mg) over 52 weeks. Improvement in micturition variables was maintained with mirabegron 50 mg from weeks 8 to 52.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Young Adult

To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder (OAB).. Patients ≥18 years with OAB symptoms were recruited to a 2-week, single-blind, placebo run-in. Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were randomized 1:1:1 to once-daily mirabegron 25 mg or 50 mg, or placebo for 12 weeks. Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours. Key secondary endpoints were changes to final visit in mean volume voided or micturition, change to week 4 in mean number of incontinence episodes and micturitions per 24 hours, changes to final visit in mean level of urgency, number of urgency incontinence episodes, and urgency (grade 3 or 4) episodes per 24 hours. Patient-reported outcomes were assessed using the OAB-questionnaire, Patient Perception of Bladder Condition, and Treatment-Satisfaction-Visual Analog Scale.. Both mirabegron groups demonstrated statistically significant improvements in coprimary endpoints vs placebo. Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following: change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours. Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo.. Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency. Mirabegron was well tolerated vs placebo.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Double-Blind Method; Female; Headache; Humans; Hypertension; Male; Middle Aged; Severity of Illness Index; Tachycardia; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Mirabegron, a β(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB).. To assess the efficacy and tolerability of mirabegron versus placebo.. Multicenter randomised double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients ≥ 18 yr of age with symptoms of OAB for ≥ 3 mo.. After a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50mg, mirabegron 100mg, or tolterodine extended release 4 mg orally once daily for 12 wk.. Patients completed a micturition diary and quality-of-life (QoL) assessments. Co-primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24h. The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo. Safety parameters included adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, and postvoid residual volume.. A total of 1978 patients were randomised and received the study drug. Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements (adjusted mean change from baseline [95% confidence intervals]) at the final visit in the number of incontinence episodes per 24h (-1.57 [-1.79 to -1.35] and -1.46 [-1.68 to -1.23], respectively, vs placebo -1.17 [-1.39 to -0.95]) and number of micturitions per 24h (-1.93 [-2.15 to -1.72] and -1.77 [-1.99 to -1.56], respectively, vs placebo -1.34 [-1.55 to -1.12]; p<0.05 for all comparisons). Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes. The incidence of treatment-emergent AEs was similar across treatment groups. The main limitation of this study was the short (12-wk) duration of treatment.. Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability. TRIAL IDENTIFICATION: This study is registered at ClinicalTrials.gov, identifier NCT00689104.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Australia; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Europe; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Single-Blind Method; Surveys and Questionnaires; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urination

Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a β(3)-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials.. To assess the 12-mo safety and efficacy of mirabegron.. Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo.. After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50mg, mirabegron 100mg, or tolterodine extended release (ER) 4 mg for 12 mo.. Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms.. A total of 812, 820, and 812 patients received mirabegron 50mg, mirabegron 100mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and -0.5mm Hg for mirabegron 50mg, 100mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation.. The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period.. ClinicalTrials.gov identifier: NCT00688688.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Headache; Humans; Hypertension; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Single-Blind Method; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urinary Retention; Xerostomia

The Brazilian public health system does not cover pharmacotherapy for urge urinary incontinence (UUI). The aim of this study was to estimate the cost-effectiveness and budget impact of providing tolterodine, solifenacin, oxybutynin (OXY), darifenacin, and mirabegron for the treatment of UUI in Brazilian public health system.. A cost-effectiveness analysis with budget impact was performed. Six scenarios were assessed: in one scenario, all 5 therapeutic alternatives approved for coverage, and in the remaining 5 scenarios, only 1 alternative is approved for adoption for all patients. Clinical data were derived from a rapid systematic review conducted in several databases. One-way sensitivity analysis was also performed. The time horizon was 12 months.. The cost-effectiveness analysis showed that patients treated with OXY had the lowest incremental cost-effectiveness ratio (ICER) per outcomes assessed (change in urinary incontinence episodes (UIE): R$1180.08; change in urge incontinence episodes: R$757.85 and change in micturition frequency: R$907.75), corresponding to a budget impact of R$17.9 billion over 5 years. The change in effectiveness measures was the parameter that most influenced the results of the ICER per patient-year.. The results of the study have shown that OXY and solifenacin had the lowest ICER per patient-year and the lowest budget impact when compared with other drugs.

Topics: Acetanilides; Adult; Brazil; Cost-Benefit Analysis; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Public Health; Thiazoles; Urinary Incontinence, Urge; Urological Agents

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Clinical Trials as Topic; Humans; Research Design; Thiazoles; Urinary Incontinence, Urge

Mirabegron interacts with many other drugs via cytochrome P450 isoenzymes. It also has additive adverse effects, in particular cardiac disorders, when combined with antimuscarinic drugs. In view of animal data and the lack of clinical data, mirabegron should not be used by women who are or may be pregnant. In practice, drugs have little value in treating urinary urgency attributed to "overactive bladder". The risk of adverse drug reactions is rarely justified, even when the disorder is severe. Antimuscarinic disorders, such as dry mouth, are less frequent with mirabegron than with antimuscarinic drugs. Like antimuscarinic drugs, mirabegron can cause cardiac arrhythmias, especially tachycardia. Mirabegron may also cause a dose-dependent increase in blood pressure. Other adverse effects include rare cases of kidney stones and rare but sometimes serious skin reactions. When a treatable cause of urinary urgency with incontinence has been ruled out and non-drug measures have failed, recourse to an antimuscarinic drug is slightly effective but exposes patients to numerous, potentially severe adverse effects. Mirabegron (Betmiga⁰, Astellas Pharma), a beta-3 adrenergic receptor agonist, is authorised for use in this setting in the European Union. Clinical evaluation of mirabegron is mainly based on five randomised, double-blind trials versus antimuscarinic drugs, lasting 3 to 12 months and including about 8000 patients with urinary urgency. Mirabegron and the antimuscarinic comparators were similarly effective, even after antimuscarinic drug failure. A meta-analysis of four placebo-controlled trials including about 3500 patients suggested that mirabegron was poorly effective: on average, treatment prevented one episode of urinary incontinence every 2 days.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Female; Humans; Pregnancy; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Incontinence, Urge

To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective.. A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015.. At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold.. Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain.

Topics: Acetanilides; Benzhydryl Compounds; Cost-Benefit Analysis; Delivery of Health Care; Female; Humans; Male; Middle Aged; Spain; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Urge

Urinary incontinence, the involuntary leakage of urine, can result from abnormalities of the urinary tract or may be caused by other conditions and is sub-divided into a number of classifications including stress incontinence and urge urinary incontinence.(1) Urge urinary incontinence (UUI) is involuntary urine leakage accompanied by urgency of micturition.(2) Overactive bladder (OAB) syndrome is defined as urgency occurring with or without UUI and usually occurs with frequency and nocturia.(1) Wet OAB is associated with UUI, while dry OAB is not associated with incontinence. Current drug therapy for OAB involves the use of an antimuscarinic drug, of which there are a number available, such as oxybutynin, darifenacin, solifenacin and tolterodine.(1,3) ▾Mirabegron is the first of a new class of drug, beta-3-adrenoreceptor agonists, licensed for symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with OAB syndrome.(4) Here we review the evidence for mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Female; Humans; Male; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence, Urge