mirabegron and Urinary-Incontinence

Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke.. The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder.. We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022.. A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups.. The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.

Topics: Cholinergic Antagonists; Humans; Nocturia; Pelvic Floor; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence

Lower urinary tract symptoms, including urgency, urgency incontinence, frequency, and nocturia, are highly prevalent in older adults and are associated with significant morbidity and impairment in quality of life. When conservative measures such as bladder training fail to improve symptoms, pharmacological management is recommended by national and international guidelines. Mirabegron, an agonist of the β3 adrenergic receptor, demonstrates similar efficacy to the anticholinergic drugs without the risk of anticholinergic effects, but experience and evidence in the very elderly population are limited. This narrative review examines the current evidence base for mirabegron in very elderly adults.

Topics: Acetanilides; Age Factors; Aged; Aged, 80 and over; Female; Humans; Lower Urinary Tract Symptoms; Nocturia; Patient Safety; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

The first-in-class β

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Male; Muscarinic Antagonists; Signal Transduction; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Currently, a wide range of different drugs is available for te management of overactive bladder. This creates problems when it comes to drug selection and personalized care for each patient. Mirabegron is the only 3-adrenomimetic agent for the treatment of urinary disorders, which, after careful long-term multi-center randomized trials, has been approved for use in Europe and North America. Mirabegron has proven to be very effective in patients who had previously received anticholinergic drugs and discontinued them because of the insufficient therapeutic effect or pronounced adverse reactions. However, the question of using Mirabegron as a first-line treatment for overactive bladder and the existing limitations in its administration in clinical urology practice remains open.

Topics: Acetanilides; Female; Humans; Male; Thiazoles; Urinary Bladder, Neurogenic; Urinary Incontinence

Study the efficacy and adverse events of different pharmacological lines in the treatment of idiopathic overactive bladder (iOAB).. PubMed research on meta-analyses and randomized controlled trials (RCT) focused on the efficacy and adverse effects of anticholinergics, botulinum toxin and mirabegron since 2005.. Ten meta-analyses of anticholinergics were selected; 16 randomized controlled trials (ERC) comparing botulinum toxin A to either anticholinergic or placebo and 10 ERC studying mirabegron. All the molecules studied showed efficacy compared to placebo in the treatment of iOAB. Anticholinergics remain the first-line pharmacological treatment allowing a significant reduction in the number (nb) of incontinence (-5/week) and in the number of urination (-4/week) as well as a perception of subjective improvement of the symptoms reported by 56 % of the patients treated against 41 % for the placebo group (RR: 1.39 [95 % CI: 1.28-1.51]). The most commonly reported side effect is dry mouth (30 % vs. 8 % in the placebo group). Injections of botulinum toxin A appear to be relatively comparable to anticholinergics in the first line with a decrease in urinary emergency incontinence (UTI) of 3.3/d in the toxin group versus 3.4/d in the anticholinergic group (P=0.81). There was also a higher rate of complete resolution of urinary incontinence in the toxin group (27 % vs. 13 % P=0.03) but significant adverse effects such as lower urinary tract infections (33 % vs. 13 % P>0.01). And the risk of using self-catheterization (5 % vs. 0 % P=0.01). In view of the invasive character of the toxin injections and their side effects, this treatment remains a 2nd line therapy. The same is true for mirabegron: similar efficacy (IUU number in the mirabegron group 50mg -1.74 vs. -1.53 In the solifenacin group 5mg, P>0.5) but different side effects with arterial hypertension (the oral dryness rate being comparable to that in the placebo group). The choice of use of anticholinergic or mirabegron should be based on the balance of efficacy/tolerance to be estimated for each patient.. The different molecules have shown their efficacy in the treatment of iOAB with acceptable tolerance. There is a lack of direct comparisons between treatments available. Further studies are needed to evaluate the possible interest of a combination of these molecules as well as the search for predictive factors of response to these different therapies.

Topics: Acetanilides; Botulinum Toxins, Type A; Cholinergic Antagonists; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB).. To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB.. Network meta-analysis.. A search of 9 electronic databases, review documents, guidelines and websites.. Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR).. No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis.. In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB.

Topics: Acetanilides; Botulinum Toxins, Type A; Humans; Nocturia; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

Topics: Acetanilides; Administration, Intravesical; Aged; Behavior Therapy; Botulinum Toxins, Type A; Cholinergic Antagonists; Combined Modality Therapy; Cooperative Behavior; Female; Humans; Interdisciplinary Communication; Male; Thiazoles; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence

Overactive bladder (OAB) and urinary incontinence, although not life-threatening, are very bothersome chronic health conditions. The limitations of current pharmacological treatment urge the need for novel drugs with alternative mechanisms of action. Huge efforts in this area of research led to the synthesis of several selective and potent β3-adrenoceptor agonists that gained relevance through research during the late 80s and 90s. Mirabegron was the first compound of this new class of drugs that showed preclinical efficacy in several models of storage bladder dysfunction, together with a favorable human pharmacological profile. Having passed the proof-of-concept stage, an extensive clinical development and pharmacology program was performed during the last 10 years, involving >10,000 individuals, before mirabegron was granted marketing approval.. In this case history, the authors review the milestones in mirabegron's discovery based on a systematic literature review.. Thanks to its tolerability and safety/efficacy balance, mirabegron has potential to fill a need for new treatment options for OAB, and paves the way for further development of a completely new class of drugs aimed to treat this condition. However, the exact role of mirabegron in clinical practice has yet to be defined. Further studies are needed in order to clarify, together with post-launch information, critical safety issues and cost-effectiveness in head-to-head comparison with current standard treatments.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Humans; Receptors, Adrenergic, beta-3; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urinary Tract; Urological Agents

mirabegron is a β3-adrenoceptor agonist developed for the treatment of symptoms of overactive bladder (OAB). As the prevalence of OAB increases with age, a prospective subanalysis of individual and pooled efficacy and tolerability data from three 12-week, randomised, Phase III trials, and of tolerability data from a 1-year safety trial were conducted in order to evaluate the efficacy and tolerability of mirabegron in subgroups of patients aged ≥65 and ≥75 years.. primary efficacy outcomes were change from baseline to final visit in the mean number of incontinence episodes/24 h and the mean number of micturitions/24 h. Tolerability was assessed by the incidence of treatment-emergent adverse events (TEAEs).. over 12 weeks mirabegron 25 mg and 50 mg once-daily reduced the mean numbers of incontinence episodes and micturitions/24 h from baseline to final visit in patients aged ≥65 and ≥75 years. Mirabegron was well tolerated: in both age groups, hypertension and urinary tract infection were among the most common TEAEs over 12 weeks and 1 year. The incidence of dry mouth, a typical anticholinergic TEAE, was up to sixfold higher among the older patients randomised to tolterodine than any dose of mirabegron.. these analyses have demonstrated the efficacy of mirabegron over 12 weeks and the tolerability of mirabegron over 12 weeks and 1 year in OAB patients aged ≥65 and ≥75 years, supporting mirabegron as a therapeutic option in older patients with OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Age Factors; Aged; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

Overactive bladder is defined by ICS as urgency frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection, or other obvious causative pathology Lower urinary tract symptoms (LUTS) are highly prevalent, especially in aging populations. Epidemiological studies reported LUTS in 62% of men and 67% of women, rising to 81% and 79%, respectively in adults over 60 years old. However the actual burden of LUTS remains relatively unrecognized. LUTS, mainly due to considerable distress including almost all aspects of social functioning, impact on sleep and mental health, may significantly affect quality of life. Management of LUTS including OAB has undergone dramatic changes since 1972, when the first antimuscarinic drug-oxybutynin, was introduced into clinical practice. In the last two decades, six new antimuscarinic drugs entered OAB field and this was accompanied by introduction of botulinum toxin into clinical practice in patients resistant to or not compliant with antimuscarinics. Nowadays, it is recognized that OAB is progressive, age-related and non sex-specific condition with most patients experiencing a combination of storage, voiding and post-micturition symptoms. In 2013, the next step was taken, with new therapeutic options for OAB, enabling an even more patient-tailored approach. This was possible for both, male and female OAB sufferers with new class of oral 3 adrenoreceptor agonist (mirabegron). This drug, by stimulation of 3-adrenoceptors, couples via Gs proteins to adenylyl cyclase, what results in an increase of intracellular cAMP levels and a subsequent activation of cAMP-dependent protein kinase A, which then phosphorylates myosin light chain kinase responsible for inhibition of calcium-calmodulin dependent interaction of myosin with actin. Moreover the cAMP increase also leads to the reduction of cytoplasmic Ca2+ concentration by removal of calcium ions from cytoplasm. These both actions result in a significant increase in the storage bladder capacity and by this interval between micturitions is prolonged. Mirabegron was evaluated in three 12-week, double blind, randomized, placebo controlled, parallel-group, multicenter clinical trials in OAB patients with symptoms of urge urinary incontinence, urgency and frequency - study 046, 047 and 074. It should be pointed out that efficacy of mirabegron was maintained through the entire 12-month period in phase Ill long-term study Discoveries on the phy

Topics: Acetanilides; Adrenergic beta-3 Receptor Antagonists; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence

To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB).. A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis.. We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, -2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB-q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04).. In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB.

Topics: Acetanilides; Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Odds Ratio; Phenylpropanolamine; Prospective Studies; Research Design; Software; Surveys and Questionnaires; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.. This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate).. Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine.. The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents; Young Adult

Mirabegron (YM-178), currently in development by Astellas Pharma Inc, is an orally active β₃-adrenoceptor (AR) agonist for the potential symptomatic treatment of overactive bladder (OAB). Mirabegron demonstrates nanomolar EC50 values against the human β₃-AR in biochemical assays with potent selectivity over the β₁- and β₂-ARs. Originally developed as a treatment for diabetes, the development of mirabegron was later refocused to OAB. Cystometric experiments in rats reported a reduction in resting intravesical pressure and contraction frequency in anesthetized rats, without any effect on the amplitude of micturition contraction. Mirabegron also reduced non-micturition bladder contractions in an awake rat model of bladder outlet obstruction. Top-line results from clinical trials to date indicate that mirabegron has been well tolerated with significant efficacy in reducing the number of incontinence episodes and mean micturition frequency in patients. Evidence of cytochrome P450 (CYP)2D6 inhibition in clinical trials highlighted a concern for pharmacokinetic interaction with other drugs that are CYP2D6 substrates, as confirmed by a rise in the pharmacokinetic parameters of desipramine with concomitant administration of mirabegron. Mirabegron exhibits a novel mode of action in targeting the β₃-AR for bladder relaxation, and the studies and trials conducted to date suggest mirabegron as a promising new treatment in the management of OAB symptoms, such as increased urinary urgency and frequency, and urgency incontinence.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Rats; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urination Disorders

Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive impairment, physical mobility impairment, and depression. Observational studies have raised concern about potentially higher rates of delirium and dementia in older adults taking anticholinergic bladder medications, but few prospective data are available to evaluate the effects of these and other pharmacologic treatments for urgency incontinence on cognition and other multisystem functional domains important to older women.. The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial comparing the multisystem effects of anticholinergic versus beta-3-adrenergic agonist bladder therapy and versus no active bladder anti-spasmodic pharmacotherapy in older women with urgency incontinence. Women aged 60 years and older (target N = 270) who have chronic urgency-predominant urinary incontinence and either normal or mildly impaired cognition at baseline are recruited from the community by investigators based in northern California, USA. Participants are randomized in equal ratios to take identically encapsulated oral anticholinergic bladder therapy (in the form of tolterodine 2 mg extended release [ER]), oral beta-3 adrenergic agonist bladder therapy (mirabegron 25 mg ER), or placebo daily for 24 weeks, with the option of participant-directed dose titration (to tolterodine 4 mg ER, mirabegron 50 mg ER, or matching placebo daily). Participants also receive patient-oriented information and instructions about practicing first-line behavioral management strategies for incontinence. The primary outcome is change in composite cognitive function over 24 weeks assessed by a comprehensive battery of cognitive tests, with a secondary exploration of the persistence of change at 36 weeks. Secondary outcomes include changes over 24 and 36 weeks in domain-specific cognitive function; frequency, severity, and impact of urgency-associated urinary symptoms; physical function and balance; sleep quality and daytime sleepiness; psychological function; and bowel function.. The TRIUMPH trial addresses the need for rigorous evidence to guide counseling and decision-making for older women who are weighing the potential multisystem benefits and risks of pharmacologic treatments for urgency incontinence in order to preserve their day-to-day functioning, quality of life, and independence in older age.. ClinicalTrials.gov NCT05362292. Registered on May 5, 2022.

Topics: Adrenergic Agonists; Aged; Cholinergic Antagonists; Double-Blind Method; Female; Humans; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To confirm if mirabegron 50 mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo.. Post-hoc analyses were carried out using pooled data from a Japanese phase IIb and a phase III study. The primary efficacy end-point was baseline to end-of-treatment change in the mean number of micturitions/24 h. The secondary end-points were changes in the mean voided volume/micturition, mean number of urgency and incontinence episodes/24 h, and mean number of nocturia episodes/night. Other end-points were quality of life and incontinence normalization rates.. Women with urgency urinary incontinence (placebo n  = 204, mirabegron n = 214) and mixed urinary incontinence (placebo n = 122, mirabegron n = 139) were included. Change in mean micturitions/24 h at end-of-treatment for mirabegron was statistically significant versus placebo in both populations; the effect size increased over time. For all secondary end-points, median changes for mirabegron were statistically significant versus placebo at end-of-treatment, except for nocturia for the urgency urinary incontinence population and urgency for the mixed urinary incontinence population. Mirabegron showed larger improvements versus placebo in all quality-of-life domains, except for general health perception in the urgency urinary incontinence population. Incontinence normalization rates for mirabegron were 47.2% and 49.6% in the urgency urinary incontinence and mixed urinary incontinence populations, respectively, versus 42.6% and 39.3% for placebo.. Mirabegron 50 mg significantly improved key overactive bladder symptoms versus placebo in women with urgency urinary incontinence, and it also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. These findings support the benefits of using mirabegron in the female overactive bladder wet population.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Double-Blind Method; Female; Humans; Japan; Muscarinic Antagonists; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To evaluate efficacy and safety of combination of tadalafil + mirabegron for overactive bladder/benign prostatic hyperplasia (OAB/BPH).. 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.. 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.. 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.

Topics: Acetanilides; Aged; Aged, 80 and over; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Prostatic Hyperplasia; Tadalafil; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

In older patients with overactive bladder (OAB), mirabegron, a β. Our objective was to further examine the safety and tolerability of mirabegron versus placebo treatment in patients aged ≥ 65 years with OAB-wet.. We conducted a 12-week, double-blind, randomized, placebo-controlled phase IV study to compare mirabegron with placebo. Community-dwelling patients aged ≥ 65 years with OAB-wet (one or more incontinence episode and three or more urgency episodes, and an average of eight or more micturitions/24 h over a 3-day diary) were randomized to receive placebo or mirabegron 25 mg/day (optional dose escalation to 50 mg/day at week 4 or 8). Safety analyses were performed for adverse events (AEs) and vital signs on all randomized patients who received one or more dose of study drug.. Treatment-emergent AEs (TEAEs), the majority mild or moderate in severity, were reported in 39.4% of placebo patients and 44.2 and 49.8% of those who received mirabegron 25 mg or 50 mg, respectively. The most common TEAEs in mirabegron-treated patients were urinary tract infection, headache, and diarrhea. The incidence of TEAEs was slightly higher in mirabegron patients aged ≥ 75 years than in those aged < 75 years. There were no clinically meaningful differences in changes in vital signs from baseline to end of treatment for any treatment group, and no differences were observed between mirabegron and placebo treatment groups. TEAEs tended to occur early post exposure and were not dose related.. Mirabegron treatment was well-tolerated in older adults with OAB-wet. Safety and tolerability were consistent with the known mirabegron safety profile.. This study is registered at ClinicalTrials.gov: NCT02216214.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Age Factors; Aged; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Female; Headache; Humans; Male; Middle Aged; Severity of Illness Index; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To investigate the efficacy and safety of mirabegron dose escalation from 25 to 50 mg in Asian patients with overactive bladder (OAB).. A total of 242 patients (mean age: 67 years) with OAB were randomized to two groups: M25 (mirabegron 25 mg daily for 12 weeks) and M50 (mirabegron 25 mg daily for 4 weeks + 50 mg daily for 8 weeks). The primary endpoint was the percentage of patients without urgency or with a reduction of ≥2 in daily urgency episodes after treatment. Secondary endpoints included OAB symptom scores and other voiding parameters. Chi-squared and Wilcoxon signed-rank tests were used for data comparison.. All OAB symptom scores in both groups improved significantly at 4 and 12 weeks. Both groups showed similar numbers of patients who reached the primary endpoint after treatment (M25: 64.6%, 42/65; M50: 64.9%, 50/77; p = 0.554). Patients in the M50 group with residual daily urgency or urgency urinary incontinence (UUI) episodes after 4 weeks of mirabegron 25 mg had a significantly higher rate of reduction in daily urgency episodes (60.9% vs. 34.5%, p = 0.034) and daily UUI episodes (87.5% vs. 37.5%, p = 0.021). Adverse event (AE) rates were similar between the groups.. Mirabegron 25 mg for 12 weeks and mirabegron dose escalation from 25 to 50 mg exerted similar therapeutic effects. However, the dose escalation further improved the daily urgency and UUI episodes in patients with residual urgency or UUI after the initial treatment with mirabegron 25 mg.

Topics: Acetanilides; Aged; Aged, 80 and over; Double-Blind Method; Female; Humans; Male; Middle Aged; Taiwan; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron.. During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions.. Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.. Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Benzilates; Blood Pressure; Constipation; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Nasopharyngitis; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Xerostomia

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).. 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.. 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.. Mirabegron and solifenacin combination therapy was a well-tolerated and effective treatment for patients with OAB symptoms irrespective of their age.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents; Young Adult

The long-term potential of solifenacin and mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed.. To evaluate the safety and efficacy of solifenacin succinate 5mg plus mirabegron 50mg tablets (combination treatment) versus solifenacin or mirabegron monotherapy in patients with OAB over 12 mo.. Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients.. The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h.. The median age was 60 yr (range 19-86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to mirabegron and solifenacin for the number of incontinence episodes (vs mirabegron: adjusted mean difference [AMD] -0.5, 95% confidence interval [CI] -0.7 to -0.2, p<0.001; vs solifenacin: AMD -0.1, 95% CI -0.4 to 0.1, p=0.002) and micturitions (vs mirabegron: AMD -0.5, 95% CI -0.8 to -0.2, p<0.001; vs solifenacin: AMD -0.4, 95% CI -0.7 to -0.1, p=0.004).. Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic.. This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

Topics: Acetanilides; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Solifenacin Succinate; Symptom Assessment; Thiazoles; Time; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To determine the effectiveness of mirabegron in patients with neurogenic lower urinary tract dysfunction.. 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.. 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.

Topics: Acetanilides; Adult; Aged; Canada; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Pilot Projects; Spinal Cord Injuries; Thiazoles; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

To evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy, with acceptable tolerability, in the general overactive bladder (OAB) population with urinary incontinence (UI).. After a 4-week placebo run-in, patients aged ≥18 years with wet OAB (urgency, urinary frequency and UI) for ≥3 months who recorded on average ≥8 micturitions/24 h, ≥1 urgency episode/24 h, and ≥3 UI episodes over the 7-day micturition diary, were eligible for randomisation to double-blind treatment [2:2:1:1:1:1 ratio, solifenacin 5 mg + mirabegron 25 mg (combined S5 + M25 group); solifenacin 5 mg + mirabegron 50 mg (combined S5 + M50 group); solifenacin 5 mg; mirabegron 25 mg; mirabegron 50 mg; or placebo for 12 weeks], and 2-weeks' single-blind, placebo run-out. Co-primary efficacy variables were change from baseline to end of treatment (EoT) in the mean number of UI episodes/24 h and micturitions/24 h, assessed using a 7-day electronic micturition diary. Secondary efficacy variables included change from baseline to EoT in the mean volume voided/micturition, change from baseline at weeks 4, 8, 12 and EoT in mean number of UI episodes/24 h, micturitions/24 h, urgency episodes/24 h, urgency UI (UUI) episodes/24 h and nocturia episodes/24 h; the percentage of patients (responders) achieving zero UI episodes/24 h at EoT in the last 7 days prior to each visit, micturition frequency normalisation (<8 episodes/24 h) at weeks 4, 8, 12 and EoT; and the number of UUI episodes and nocturia episodes in the 7-day diary. Safety assessments included incidence and frequency of treatment-emergent adverse events (TEAEs), post-void residual (PVR) urine volume, and changes from baseline in laboratory parameters.. Whilst the combined S5 + M50 group was superior to solifenacin 5 mg for UI, with a mean (standard error) adjusted difference of -0.20 (0.12) UI episodes/24 h (95% confidence interval -0.44, 0.04, P = 0.033), there was no statistical superiority vs mirabegron 50 mg [-0.23 (0.12) UI episodes/24 h; P = 0.052]. In secondary analyses, all active treatment groups had greater improvements in UI episodes/24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: -0.70 episodes/24 h; combined S5 + M50 group: -0.65 episodes/24 h) that were substantially higher than those obtained with monotherapy (range -0.37 episodes/24 h for mirabegron 25 mg to -0.45 episodes/24 h for solifenacin 5 mg). For micturitions/24 h, adjusted change from baseline to EoT was greater in the combined therapy groups vs monotherapies (combined S5 + M50 group, nominal P values 0.006 and <0.001 vs solifenacin 5 mg and mirabegron 50 mg, respectively; combined S5 + M25 group, nominal P values 0.040 and 0.001 vs solifenacin 5 mg and mirabegron 25 mg, respectively). All active treatment groups had greater improvements in the mean numbers of micturitions/24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: -0.85 micturitions/24 h; combined S5 + M50 group: -0.95 micturitions/24 h) higher than with mirabegron monotherapy (25 mg: -0.36; 50 mg: -0.39 micturitions/24 h) and solifenacin 5 mg (-0.56 micturitions/24 h). The combined S5 + M50 group was statistically significantly superior to both monotherapies at EoT for UUI episodes, urgency episodes and nocturia, with effect sizes that appeared to be additive. The combined S5 + M25 group was statistically significantly superior to mirabegron 25 mg for the same variables, except for nocturia. In responder analyses at the EoT, odds ratios in favour of both combined therapies vs monotherapies were shown for the proportion of patients with zero UI episodes and those achieving micturition frequency normalisation. There was a slightly increased frequency of TEAEs in the combined therapy groups vs monotherapies and placebo. Most of the TEAEs were mild or moderate in severity. Events indicative of urinary retention were reported slightly more frequently in the combined therapy groups vs monotherapy and placebo. PVR volume was slightly increased in the combined therapy groups vs solifenacin 5 mg, mirabegron monotherapy, and placebo groups. There were slightly higher frequencies of dry mouth,. In the largest OAB study to date, combined therapy with solifenacin 5 mg + mirabegron 25 mg and solifenacin 5 mg + mirabegron 50 mg provided consistent improvements in efficacy compared with the respective monotherapies across most of the outcome parameters, with effect sizes generally consistent with an additive effect. Although the combined S5 + M50 group did not achieve a statistically significant effect vs mirabegron 50 mg in the primary analysis of one of the co-primary endpoints (change from baseline in mean number of UI episodes/24 h), it approached statistical significance (P = 0.052), and the nominal P values for the other co-primary endpoint (micturitions/24 h) were <0.05. Most effects of combined therapy vs monotherapy were observable by week 4. The clinical relevance of the improvements seen with combined therapy for several objective OAB outcome measures was also supported by the improvements of combined therapy vs monotherapy in the responder analyses.

Topics: Acetanilides; Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Internationality; Male; Maximum Tolerated Dose; Middle Aged; Multivariate Analysis; Risk Assessment; Single-Blind Method; Solifenacin Succinate; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

The BESIDE study demonstrated that combination therapy (mirabegron and solifenacin 5mg) improved overactive bladder symptoms versus solifenacin 5mg or 10mg, and was well tolerated.. To ensure efficacy and safety is maintained in older patients (>65 yr), who usually experience greater symptom severity and comorbidities, a prespecified subanalysis stratified by age group was conducted.. Patients remaining incontinent (≥1 episode during 3-d diary) following 4-wk single-blind daily solifenacin 5mg were randomized 1:1:1 to a daily double-blind combination (solifenacin 5mg and mirabegron 25mg, increased to 50mg at wk 4), solifenacin 5mg or 10mg for 12 wk. Four cohorts stratified by age (<65 yr, ≥65 yr and < 75 yr, ≥75 yr) were investigated.. Efficacy assessments: change from baseline to end of treatment in average daily incontinence (primary) and micturition frequency (key secondary), number of incontinence episodes during the 3-d diary (key secondary), and change from baseline in average daily urgency and urgency incontinence episodes. Safety included treatment-emergent adverse events and vital signs.. Full analysis set included 2110 patients: 30.9% aged ≥65 yr and 8.9% aged ≥75 yr. At the end of treatment, daily, and 3-d incontinence daily micturitions, urgency, and urgency incontinence, were improved in each treatment group and age group; the largest reductions were observed with combination in each age cohort. There were no notable differences in vital signs or the incidence of treatment-emergent adverse events between treatment and age groups, with the exception of dry mouth, which was highest with solifenacin 10mg.. Efficacy and safety in the overall population is maintained in older (≥65 yr) and elderly (≥75 yr) patients treated with a combination of solifenacin and mirabegron, or solifenacin monotherapy; irrespective of age, combination was associated with the greatest improvement in overactive bladder symptoms.. This study investigated the effectiveness and safety of a combination of two different treatments (mirabegron 50mg and solifenacin 5mg) or solifenacin (5mg or 10mg) alone in patients aged <65 yr or ≥65 yr, and <75 yr or ≥75 yr with overactive bladder. Symptoms of overactive bladder, such as the urgent need to visit the toilet, incontinence, and frequent urination, were improved with all treatments regardless of the patient's age, but combination treatment demonstrated the greatest benefit, and was well tolerated.

Topics: Acetanilides; Aged; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Single-Blind Method; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To provide a clinical view and interpretation on the methods for analysis of incontinence in patients with overactive bladder.. 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.. 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.. 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.

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy.. To evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg.. OAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4.. The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy.. A total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001), and incontinence noted in a 3-d diary (p=0.014). Combination was noninferior to solifenacin 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated.. Adding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg.. In this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated.. ClinicalTrials.gov NCT01908829.

Topics: Acetanilides; Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Retreatment; Solifenacin Succinate; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

We investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10 mg.. Patients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8 micturitions per 24 hours with minimal important differences in OAB-q and PPBC.. Overall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 and 10 mg (OR 1.47, 95% CI 1.17-1.84, p = 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively).. Significantly more patients on the combination achieved clinically meaningful improvements in incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Solifenacin Succinate; Thiazoles; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics; Young Adult

The β3-adrenoceptor agonist mirabegron is approved for treatment of the symptoms of overactive bladder (OAB). Incontinence can be the most bothersome of OAB symptoms. Hence, we conducted a post hoc analysis of pooled data from three randomised, double-blind, placebo-controlled, 12-wk, phase 3 studies of mirabegron to evaluate the efficacy of mirabegron 50mg in incontinent OAB patients and in subgroups of patients stratified by severity of incontinence at baseline (an average of two or more [FAS-I ≥ 2 subgroup] or four or more [FAS-I ≥ 4 subgroup] incontinence episodes per 24h at baseline, where FAS-I is the full analysis set-incontinence population) and to determine correlations between measures of efficacy and disease severity. Mirabegron 50mg resulted in statistically significant improvements from baseline to final visit versus placebo in mean number of incontinence episodes, micturitions, and urgency episodes per 24h and mean volume voided per micturition in the pooled incontinent population and in the FAS-I ≥ 2 and FAS-I ≥ 4 subgroups. Treatment effect versus placebo for incontinence and urgency episodes increased with increasing severity of incontinence at baseline. Moderate correlations were seen between improvement in both frequency of incontinence episodes and micturitions and baseline incontinence and micturition frequency, respectively, with mirabegron 50mg and placebo.. Incontinence can be the most bothersome of OAB symptoms; mirabegron 50mg once daily is effective for treatment of OAB symptoms in incontinent patients, and its effect increases with increasing severity of incontinence.

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

To understand how improvements in the symptoms of overactive bladder (OAB) seen with the β3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect.. In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (≥50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (≤8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination.. Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof. These improvements versus placebo were statistically significant for all double and triple responder analyses and for all single responder analyses except PPBC. PRO measurements showed directional consistency and significant correlations, and there were also significant correlations between objective and subjective measures of efficacy.. The improvements in objective measures seen with mirabegron 50 mg translate into a meaningful clinical benefit as evident by the directional consistency seen in HRQoL measures of benefit.

Topics: Acetanilides; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.. Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n = 928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume.. Mirabegron 25, 50, 100, and 200 mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p ≤ 0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p < 0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events.. The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Incidence; Internationality; Male; Middle Aged; Quality of Life; Single-Blind Method; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Representatives of two classes of oral medication are often used to treat urgency urinary incontinence (UUI): solifenacin, an M3-receptor-selective antimuscarinic, and mirabegron, a beta-3 agonist. Two previous asynchronous drug-specific studies suggested different interactions between these medications and the urobiome despite identical methodologies, including recruitment, sample procurement, medication dose escalation strategy, determination of 12-week responders versus nonresponders, and data collection. This analysis compares data from these two studies using a uniform analytic approach.. Urine was collected aseptically via transurethral catheter from consenting participants for subsequent processing by the Expanded Quantitative Urine Culture (EQUC) protocol in two cohorts (n=50 and n=47) that were demographically similar. Species accumulation curves were generated to compare the total number of unique species detected. Indices that measure richness, evenness, and/or abundance were used to compare alpha (within sample) diversity. The Bray-Curtis Dissimilarity Index was used to determine between sample (beta) diversity.. The majority of the 40 species detected in the pre-treatment urobiomes were detected in both cohorts. Both pre-treatment urobiomes were substantially similar in species richness, evenness, and diversity. Differences in pre-treatment urobiomes were associated with treatment response for solifenacin-treated participants only. In contrast, the pre-treatment urobiomes of mirabegron-treated participants were not associated with treatment response. Changes in the post-treatment urobiomes were detected in both cohorts with an increase in richness for both solifenacin (5-mg dose only) and mirabegron.. Pre-treatment urobiome characteristics were associated with treatment response in participants treated with solifenacin, but not mirabegron. Differences exist in urobiome response after treatment with two medications that have known differences in mechanism of action.

Topics: Acetanilides; Adult; Drug Therapy, Combination; Female; Humans; Muscarinic Antagonists; Solifenacin Succinate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Topics: Acetanilides; Double-Blind Method; Female; Humans; Japan; Thiazoles; Urinary Bladder, Overactive; Urinary Incontinence

Mirabegron, a beta-3 agonist, is prescribed for urgency urinary incontinence (UUI). We assessed the correlation of symptom improvement with urobiome characteristics in adult women participants prescribed mirabegron for UUI treatment.. We enrolled participants seeking UUI treatment who selected mirabegron and agreed to participate in this 12-week, open label study conducted at the Female Pelvic Medicine and Reconstructive Surgery Center at Loyola University Medical Center. Following eligibility screening and research consent, participants completed the overactive bladder questionnaire (OAB-Q) and provided a catheterized urine sample at baseline, 4, 8, and 12 weeks. The primary outcome, symptom improvement at 12 weeks, was based on the validated Patient Global Symptom Control questionnaire score to dichotomize symptom response (responder vs nonresponder [PGSC score ≤3]). Urine samples were processed by the Expanded Quantitative Urine Culture (EQUC) protocol.. Eighty-three participants (mean age 68 years) completed baseline assessment. Of the 47 participants with primary outcome data and samples analysis, there were 16 responders and 31 nonresponders; responder groups were similar demographically. Living microbes were detected in most participants. There were no significant differences in alpha diversity (within sample) at baseline between groups. However, at the 12-week follow-up, the responder urobiome became significantly richer, with a larger number of genera (p = 0.027) and was significantly more diverse than the nonresponders.. Longitudinal urobiome changes are associated with symptom improvement in adult women being treated with mirabegron for UUI. The mechanism for symptoms improvement may relate to the detected changes in the urobiome and warrants further study.

Topics: Acetanilides; Adult; Aged; Female; Humans; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Overactive bladder (OAB) is associated with physical, emotional, and financial burden. After failed conservative measures, second-line therapy includes medications, such as antimuscarinics and beta-3 adrenergic receptor (β3AR) agonists. Antimuscarinics are most commonly prescribed but have systemic side effects that lead to poor compliance. β3AR agonists include mirabegron and vibegron. Mirabegron is a first-generation β3AR agonist that is effective for frequency, urgency urinary incontinence (UUI) and urgency, but has interactions with cytochrome P450 enzymes (CYPs) and cardiovascular sequelae. Vibegron is a second-generation β3AR agonist that is highly selective and does not interact with CYPs. It is effective for reducing UUI episodes and daily micturition number and has a favorable side effect profile.. Clinical background, pharmacology, and clinical studies for vibegron.. Vibegron is a welcomed addition to the OAB therapeutic landscape. This single dose, once daily option is effective, especially for patients with wet OAB, with a favorable side effect profile. Sub-analyses of patients ≥ 65 years have shown continued efficacy and safety. The few drug interactions are of benefit, especially for older patients with polypharmacy. As long-term data accrues, vibegron has the potential to drive the OAB therapeutic market.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Receptors, Adrenergic, beta-3; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Stress-type and urgency-type urinary incontinence are seen together in mixed-type urinary incontinence. Treatment is usually chosen according to the predominant type of incontinence. The aim of this study is to evaluate the effect of mirabegron and duloxetine combination in the treatment of mixed-type urinary incontinence.. The data of 88 mixed-type urinary incontinence patients who applied to the urology outpatient clinic between January 2018 and December 2019 were retrospectively analyzed. We applied mirabegron and duloxetine treatment to the patients. The International Consultation of Incontinence Questionnaire-Short Form, Overactive bladder symptom score questionnaire and daily pad count were statistically evaluated before and after the treatment.. Statistically significant improvements were observed using the questionnaire forms and decreased daily pad usage after the eight-week treatment (p<0.001). Based on the clinical global effect scale, 62.50% of patients had a partial or complete response to treatment and also the use of daily pads were decreased from 3.7-0.89 on an average.. Combination use of mirabegron and duloxetine in the treatment of mixed-type urinary incontinence improved symptom scores and decreased pad usage.

Topics: Acetanilides; Double-Blind Method; Duloxetine Hydrochloride; Humans; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Older people, especially women, have the highest known prevalence of urinary incontinence (UI) of any other age-group. Continual care provision for elderly incontinent females is an incredibly arduous process, yet only very few studies have investigated the issue. Aim of the study was to evaluate the impact of mirabegron's treatment on the degree of burden experienced by caregivers of elderly female patients with UI.. A hundred and eighty-six caregivers of older females with mixed or urgency UI besides various conditions (strokes, post-operative recovery after major surgery, etc.) were included in the study. Group A comprised 91 patients that did not want to receive any treatment for UI. Group B consisted of 95 elderly females treated for UI with mirabegron 50 mg/daily for three months. All caregivers completed the Zarit Burden Scale (ZBS) questionnaire at the outset and after the three months. All patients completed a bladder diary at the beginning and at the end of the observation/medication period.. Patients receiving mirabegron presented a statistically significant improvement in UI parameters. Their caregivers showed a statistically significant decrease in the ZBS total score as well as separate domains.. This pilot study confirms that mirabegron administration can improve the quality of life of older females suffering from UI while substantially relieving caregiver burden. Recognizing the physical and emotional reactions of caregivers may help health providers deliver better support and resources to meet the needs of caregivers and patients alike.

Topics: Acetanilides; Aged; Caregiver Burden; Caregivers; Female; Humans; Outcome Assessment, Health Care; Pilot Projects; Quality of Life; Surveys and Questionnaires; Thiazoles; Urinary Incontinence; Urological Agents

We investigated the satisfaction and efficacy of mirabegron in patients with overactive bladder (OAB) symptoms who were unsatisfied with previous antimuscarinic treatment.. 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.. 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.. Mirabegron improved the rates of treatment satisfaction and symptoms in patients with OAB who were unsatisfied with prior antimuscarinic treatment.

Topics: Acetanilides; Aged; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Prospective Studies; Retreatment; Surveys and Questionnaires; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

 1/2019 we presented an update of the AWMF guideline 'urinary incontinence in frail elderly - diagnostics and therapy'. Since its introduction in 2015 the guideline has been under a continuous revision process by the working group 'Incontinence' of the German Society for Geriatrics (DGG). From this guideline which is accredited as an official guideline of the DGG we present here the chapter about pharmacological therapy..  A profound literature search was done in a structured evaluation process in the context of a 'frail elderly'. Most medical societies define a 'frail elderly' as someone older than 70 years and multimorbide or older than 80y. We focused on randomized, double blind, placebo controlled studies as well as already published guidelines in this field. In the case no studies were available or not feasible other publications such as not randomized studies or case reports were taken into consideration for our guideline. Recommendations resulted from a structured voting process and the results are stated as percentage of members who agreed..  Pharmacological therapy of OAB, stress incontinence and overflow incontinence as well as unspecific treatment with antidiuretics was evaluated with special focus on vulnerable, potentially cognitively impaired frail elderly. We took a closer look on special side effect profile of the above mentioned drugs with regard to the individual multimorbidity and multimedication..  Pharmacological therapy of urinary incontinence in frail elderly needs strict indication. Knowledge about drug metabolization and substance interactions as well as close monitoring of possible side effects are indispensable in this vulnerable group of patients..  1/2019 wurde ein update der seit 2005 in AWMF eingestellten und fortlaufend aktualisierten Leitlinie „Harninkontinenz bei geriatrischen Patienten – Diagnostik und Therapie“ durch die interdisziplinäre Arbeitsgruppe „Harninkontinenz“ der Deutschen Gesellschaft für Geriatrie (DGG) publiziert. Aus dieser Leitlinie, die als offizielle Leitlinie DGG akkreditiert ist, stellt der vorliegende Artikel das Kapitel „Medikamentöse Therapie“ dar..  In einem strukturierten Bewertungsprozess identifizierte eine Literaturrecherche zunächst die vorhandene Literatur im Kontext des „geriatrischen Patienten“, wie er als zumeist über 70jährig und multimorbid oder über 80jährig durch die Fachgesellschaften definiert ist. Primäre Berücksichtigung fanden randomisierte, doppelblinde, plazebokontrollierte Studien sowie bereits vorhandene Leitlinien zum Thema. Wo keine solchen Untersuchungen vorlagen oder aus methodischen Gründen prinzipiell nicht durchführbar sind, wurden auch Publikationen anderen Designs (nicht randomisierte Untersuchungen, Fallkontrollstudien) zur Leitlinienerstellung herangezogen. Die daraus resultierenden Leitlinienempfehlungen wurden in einem strukturierten Abstimmungsprozess unterzogen; das Ergebnis ist in Prozent der zustimmenden Gruppenmitgliedern angegeben..  Die medikamentöse Therapie der Überaktiven Blase, der Belastungsharninkontinenz und der Überlaufinkontinenz sowie die unspezifische medikamentöse Therapie mit Antidiuretika wurde vor dem besonderen Hintergrund des vulnerablen, potentiell kognitiv eingeschränkten und im Rahmen der Multimorbidität und Multimedikation durch Medikamenteninteraktionen besonders gefährdeten Patienten betrachtet. Dabei fand das relevante Nebenwirkungsprofil der eingesetzten Substanzen besondere Berücksichtigung..  Eine medikamentöse Therapie der Harninkontinenz bedarf bei den besonders vulnerablen, häufig multimedizierten Patienten eine besonders sorgfältige Indikationsstellung und Überwachung in Kenntnis des spezifischen Risiko- und Nebenwirkungsprofils der eingesetzten Substanzen.

Topics: Acetanilides; Aged; Botulinum Toxins; Cholinesterase Inhibitors; Duloxetine Hydrochloride; Female; Frail Elderly; Humans; Male; Muscarinic Antagonists; Practice Guidelines as Topic; Societies, Medical; Thiazoles; Urinary Incontinence

To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB).. Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis.. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032).. Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Long-Term Care; Male; Middle Aged; Product Surveillance, Postmarketing; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Interactions; Dystonia; Female; Humans; Middle Aged; Posture; Thiazoles; Urinary Incontinence

To assess the cost-effectiveness of mirabegron 50 mg relative to tolterodine extended release 4 mg for the treatment of overactive bladder if used as the first-line treatment in Japan.. A Markov model was developed to simulate the cost-effectiveness of the mirabegron first-line treatment (and tolterodine second-line) versus tolterodine first-line treatment (and mirabegron second-line) taken for 5 years from the randomized European-Australian study (SCORPIO trial) and single technology appraisal assessment report by the National Institute for Health and Care Excellence. The incremental cost-effectiveness ratio was calculated with utility value by quality-adjusted life year with cost using the medical fee and the drug price tariff in 2016. For the study of transition of treatment status, our analytical model was established. The transition probabilities of severity states were calculated based on the probabilities for the mean numbers of incontinence episodes/day and micturition episodes/day in mirabegron-treated and tolterodine-treated patients in the single technology appraisal assessment report.. The 5-year expected effect per patient was 3.860 quality-adjusted life years for first-line mirabegron and 3.839 quality-adjusted life years for first-line tolterodine. The 5-year expected cost per patient was ¥526 191 for first-line mirabegron, and ¥472 390 for first-line tolterodine. The incremental cost-effectiveness ratio was ¥2 565 927/quality-adjusted life year. This value was below the willingness-to-pay threshold of ¥5 million/quality-adjusted life year. In more severe states, the incremental cost-effectiveness ratio exceeded ¥5 million.. First-line mirabegron appears to be more cost-effective than first-line tolterodine. In patients with severe symptoms, first-line mirabegron is not economically preferable.

Topics: Acetanilides; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Costs; Humans; Japan; Markov Chains; Muscarinic Antagonists; Quality of Life; Severity of Illness Index; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Multiple sclerosis (MS) is the commonest progressive neurological disease affecting young people. With advancing disease, management of neurogenic detrusor overactivity (NDO) based on antimuscarinics may prove inadequate and if based on botulinum toxin, may necessitate clean intermittent self-catheterization. The aim of the study was to evaluate the effectiveness of combined mirabegron and desmopressin administration in the treatment of NDO in patients with MS.. Sixty patients diagnosed with MS and NDO were evaluated. All had received treatment with solifenacin 10 mg/daily for 3 months and were displeased with the results. Patients were divided in four groups. In Group A (n = 15) patients continued receiving solifenacin 10 mg/daily; in Group B (n = 15) patients received mirabegron 50 mg/daily; in Group C (n = 15) patients received desmopressin 120 mcg/daily and in Group D (n = 15) patients received mirabegron 50 mg/daily and desmopressin 120 mcg/daily. All patients were assessed with a 3 day bladder diary at the beginning and at the end of the treatment.. All patients in Groups A, B and C did not demonstrate statistically significant changes at the end of the treatment period in their 3 day bladder diary and in the presence of urinary infections. In Group D, a statistically significant improvement was noted in the mean change from baseline to end of treatment in micturition episodes (3.5 +/- 0.4 micturition/24h), in urgency episodes (2.3 +/- 0.2) and mean number of urinary incontinence (1.0 +/- 0.2 episodes/24h).. Treatment with mirabegron and desmopressin revealed both effectiveness and safety in patients with NDO and MS.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Antidiuretic Agents; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Muscarinic Antagonists; Retreatment; Solifenacin Succinate; Thiazoles; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Urination

Antimuscarinics are the pharmacologic mainstay of overactive bladder (OAB) management, but side effects limit their use. Mirabegron, a new molecule with a distinct mechanism of action (β3-adrenoreceptor agonist), was recently approved as monotherapy for idiopathic OAB in adults but has not been studied in the pediatric population.. To evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with idiopathic OAB who were refractory to and/or intolerant of antimuscarinics.. A prospective off-label study using mirabegron was conducted. Pediatric patients without symptom improvement under behavioral and medical therapies and/or with significant side effects with at least two different antimuscarinic agents were recruited.. Our primary outcome was better reported efficacy than with the use of prior anticholinergic medication. Secondary end points were tolerability, safety, and satisfaction. Efficacy and tolerability were assessed with voiding diaries, postvoid residuals, urine cultures, electrocardiogram, and vital signs. Families were questioned for continence, side effects, compliance, and Patient Perception of Bladder Condition (PPBC) questionnaire. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis.. A total of 58 patients were recruited at a median age of 10.1 yr and were on mirabegron for a median of 11.5 mo. Median bladder capacity improved from 150ml to 200ml (p<0.001). Continence improved in 52 of 58, with 13 being completely dry. Median PPBC improved from 4.0 to 2.0 (p<0.001). Eight patients reported mild or moderate side effects. Absence of a placebo group is a limitation of the study.. Mirabegron, a novel first-in-class therapy, appeared as a safe and effective alternative for children with idiopathic OAB refractory to antimuscarinics.. We evaluated the efficacy and safety of mirabegron to treat incontinence in pediatric patients. Continence, median voided volumes, and quality of life were improved after the introduction of mirabegron, and few side effects were reported.

Topics: Acetanilides; Adolescent; Adrenergic beta-3 Receptor Agonists; Child; Female; Humans; Male; Muscarinic Antagonists; Off-Label Use; Patient Satisfaction; Pilot Projects; Prospective Studies; Retreatment; Surveys and Questionnaires; Thiazoles; Treatment Failure; Urinary Bladder, Overactive; Urinary Incontinence

Topics: Acetanilides; Humans; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Hypertension; Stroke; Thiazoles; Urinary Incontinence

The first class of oral pharmacologic treatments for overactive bladder (OAB) are antimuscarinics that are associated with poor persistence, anticholinergic adverse events, and increased anticholinergic burden (ACB) with risk of cognitive impairment. Mirabegron, a β3-adrenoceptor agonist, is an oral treatment that does not contribute to ACB and has early evidence of improved persistence. The objective of the analysis was to assess the cost-effectiveness of mirabegron for OAB vs six antimuscarinics in the US.. A Markov state-transition model assessed US commercial health-plan and Medicare Advantage perspectives over a 3-year time horizon in an OAB patient population. Transition probabilities between five micturition and five incontinence severity states were derived from a network meta-analysis of 44 trials of oral OAB treatments. Therapy beginning with an oral OAB agent could discontinue or switch to another oral agent and could be followed by tibial nerve stimulation, sacral neuromodulation, or onabotulinumtoxinA. The primary outcome was cost per quality-adjusted life year (QALY). Utilities were mapped from incontinence and micturition frequencies as well as demographics. Based on analysis of data from a large healthcare system, elevated ACB was associated with increased healthcare utilization and probability of cognitive impairment.. From both commercial and Medicare Advantage perspectives, mirabegron was the most clinically effective treatment, while oxybutynin was the least expensive. Tolterodine immediate release (IR) was also on the cost-effectiveness frontier. The analysis estimated costs per QALY of $59,690 and $66,347 for mirabegron from commercial health plan and Medicare Advantage perspectives, respectively, compared to tolterodine IR. Other antimuscarinics were dominated.. This analysis estimated that mirabegron is a cost-effective treatment for OAB from US commercial health plan and Medicare Advantage perspectives, due to fewer projected adverse events and comorbidities, and data suggesting better persistence.

Topics: Acetanilides; Cost-Benefit Analysis; Economics, Pharmaceutical; Female; Humans; Male; Markov Chains; Medicare Part C; Muscarinic Antagonists; Thiazoles; United States; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

Topics: Acetanilides; Botulinum Toxins, Type A; Humans; Mandelic Acids; Suburethral Slings; Thiazoles; Transdermal Patch; Urinary Incontinence; Urological Agents

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Aprepitant; Female; Humans; Morpholines; Pyrazoles; Receptors, Neurokinin-1; Thiazoles; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics