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Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial.

ABSTRACT: Antimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a ?3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-controlled Phase 3 trial conducted in Europe and Australia (NCT00689104), mirabegron 50 mg and 100 mg resulted in statistically significant reductions from baseline to final visit, compared with placebo, in the co-primary end points - mean number of incontinence episodes/24 h and mean number of micturitions/24 h. We conducted a post hoc, subgroup analysis of this study in order to evaluate the efficacy of mirabegron in treatment-naïve patients and patients who had discontinued prior antimuscarinic therapy because of insufficient efficacy or poor tolerability.Patients were randomized to placebo, mirabegron 50 or 100 mg, or tolterodine extended release (ER) 4 mg orally, once-daily, for 12 weeks. For the post hoc analysis, the primary patient population was divided into the following subgroups: (1) patients who had not received any prior antimuscarinic OAB medication (treatment-naïve) and (2) patients who had received prior antimuscarinic OAB medication. The latter subgroup was further subdivided into patients who discontinued due to: (3) insufficient efficacy or (4) poor tolerability. Analysis of the co-primary efficacy endpoints by subgroup was performed using analysis of covariance with treatment group, subgroup, sex, geographical region, and subgroup-by-treatment interaction as fixed factors; and baseline value as a covariate.Mirabegron, 50 mg and 100 mg once-daily, demonstrated similar improvements in the frequency of incontinence episodes and micturitions in OAB patients who were antimuscarinic-naïve and who had discontinued prior antimuscarinic therapy. While mirabegron demonstrated improvements in incontinence and micturition frequency in patients who had discontinued prior antimuscarinic therapy due to insufficient efficacy, the response to tolterodine was similar to that of placebo.In this post hoc subgroup analysis, mirabegron provided treatment benefits in OAB patients who were antimuscarinic treatment-naïve and in patients who had received prior antimuscarinic treatment.

SUBMITTER: Khullar V

PROVIDER: S-EPMC3849064 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial.

Khullar Vik V Cambronero Javier J Angulo Javier C JC Wooning Marianne M Blauwet Mary Beth MB Dorrepaal Caroline C Martin Nancy E NE

BMC urology 20130918

<h4>Background</h4>Antimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a β3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-cont ...[more]

PMID: 24047126

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Project description:ObjectivesThe aim of this study was to evaluate the cost effectiveness of mirabegron relative to two antimuscarinics, oxybutynin extended release (ER) and tolterodine ER, in patients with overactive bladder (OAB) from the perspective of a third-party payer in Colombia.MethodsA Markov model simulated the therapeutic management, disease course, and complications in hypothetical cohorts of OAB patients over a 5-year period. The model predicted costs and three outcomes: quality-adjusted life-years (QALYs), micturition state improvement (MSI), and incontinence state improvement (ISI). In each 1-month cycle, patients could transition between different health states reflecting symptom severity. Transition probabilities were estimated from a published mirabegron trial and mixed treatment comparison. Other inputs such as treatment discontinuation based on treatment-specific rates of persistence, resource use and costs, anticholinergic burden, comorbidity treatment, and drug acquisition were obtained from Società Italiana Scienze Mediche, Instituto de Seguros Sociales Tariff Manual, published literature, and expert opinion. Deterministic and probabilistic sensitivity analyses were conducted. Costs are presented in 2017 Colombia Pesos (COP).ResultsMirabegron was cost effective for all outcome measures at a willingness-to-pay threshold of 124,919,725 COP, which is three times the per capita gross domestic product (GDP). Using QALYs as the measure of effect, mirabegron had an incremental cost-effectiveness ratio (ICER) of 85,802,036 COP/QALY (26,365 USD/QALY) and 66,360,134 COP/QALY (20,384 USD/QALY) versus oxybutynin and tolterodine, respectively. Probabilistic sensitivity analyses showed that mirabegron was cost effective in 99.5% and 100% of simulations compared with oxybutynin and tolterodine, respectively. Using MSI and ISI as the measure of effects yielded ICERs below one GDP.ConclusionsMirabegron is a cost effective alternative to oxybutynin and tolterodine from the perspective of a third-party payer in Colombia.

Project description:IntroductionMATCH was a randomized, double-blind, placebo-controlled study enrolling Japanese and Korean men aged???40 years who still had overactive bladder (OAB) symptoms while receiving tamsulosin. After a 4-week single-blind screening period in which patients received placebo and tamsulosin, patients were randomized to mirabegron 50 mg?+?tamsulosin or placebo?+?tamsulosin for 12 weeks (n?=?568). This post hoc analysis investigated the proportion of treatment responders for each treatment group and for subgroups stratified by age based on voiding diaries and patient-reported outcomes (PROs).MethodsResponders were defined as those achieving normalization or clinically meaningful improvements in efficacy, or clinically important differences in PROs [??10-point improvement in OAB questionnaire (OAB-q) symptom bother or total health-related quality of life (HRQoL) subscales at end of treatment (EoT; minimally important difference [MID]) or OAB symptom score (OABSS) total score decreased by???3 points at EoT [minimally clinically important change (MCIC)]].ResultsAt EoT, micturition frequency normalization was achieved by 30.7% of tamsulosin?+?mirabegron patients and 18.6% of tamsulosin?+?placebo patients. Normalization of urgency and incontinence was 19.1% and 60.7% for tamsulosin?+?mirabegron and 18.2% and 60.0% for tamsulosin?+?placebo. Normalization of OAB symptoms based on OABSS was 17.1% for tamsulosin?+?mirabegron and 14.5% for tamsulosin?+?placebo. Higher proportions of patients in the mirabegron add-on group versus the placebo group reported clinically meaningful improvements in micturitions, urgency, and incontinence and in MCIC for OABSS and MID for the OAB-q subscales. Double- and triple-responder findings were as predicted by the results of single-responder analyses. These results were mirrored in the age groups using cut-offs of 65 and 75 years.ConclusionMirabegron therapy added on to tamsulosin resulted in a higher frequency of responders in terms of normalization (e.g., micturition frequency normalization), clinically meaningful improvements in efficacy (e.g.,???50% decrease in urgency), and minimally important changes in PROs (e.g., MCIC in OABSS).Trial registrationClinicalTrials.gov identifier, NCT02656173.

Project description:IntroductionPatient-reported outcomes (PROs) provide valuable insights about the effectiveness of overactive bladder (OAB) treatments. The aim of PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder) was to provide real-world evidence from the USA and Canada on patient-perceived effectiveness and safety of mirabegron and antimuscarinics for treating OAB symptoms.MethodsThis prospective, non-interventional registry followed adult patients with OAB who were starting treatment with mirabegron or antimuscarinics. All treatment decisions were made at the discretion of the treating healthcare provider with no mandatory visits after enrollment. The primary objective was to identify factors associated with improved treatment effectiveness from a patient perspective mainly using the OAB Questionnaire Short-Form (OAB-q SF). The form was sent to patients via email link at baseline and months 1, 3, 6, and 12. Treatment-emergent adverse event (TEAE) data were collated from investigator reports.ResultsOverall, 1514 patients were included (female 73.5%, mean age 62.2 years). Mirabegron was initiated by 613 patients and antimuscarinics by 901 patients. A PRO response rate of approximately 60% was achieved (575 patients did not complete baseline PROs). Similar improvements in OAB-q SF symptom bother score and health-related quality of life (HRQoL) total score were observed for mirabegron and antimuscarinic initiators. Covariate-adjusted models demonstrated that worse baseline PRO score, Hispanic ethnicity, being treatment naïve, and use of complementary/supportive OAB therapies at baseline were significantly associated with greater improvements in both scores. The most frequent TEAEs were gastrointestinal disorders (dry mouth, constipation, and nausea) and nervous system disorders (headache, somnolence, and dizziness).ConclusionThere are no differences between mirabegron and antimuscarinics in terms of patient-reported OAB symptom bother and HRQoL.Trial registrationClinicalTrials.gov identifier, NCT02386072.FundingAstellas Pharma Global Development, Inc. Plain language summary available for this article.

Project description: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.

Project description:ObjectivesThis study examined the incidence and predictors of antimuscarinic medication use including non-selective antimuscarinics among older adults with dementia and overactive bladder (OAB).MethodsThe study used a new-user cohort design involving older adults (≥65 years) with dementia and OAB based on 2013-2015 Medicare data. Antimuscarinics included non-selective (oxybutynin, tolterodine, trospium, fesoterodine) and selective (solifenacin, darifenacin) medications. Descriptive statistics and multivariable logistic regression models were used to determine the incidence and predictors of new antimuscarinic use including non-selective antimuscarinics, respectively.ResultsOf the 3.38 million Medicare beneficiaries with dementia, over one million (1.05) had OAB (31.03%). Of those, 287,612 (27.39%) were reported as prevalent antimuscarinics users. After applying continuous eligibility criteria, 21,848 (10.34%) incident antimuscarinic users were identified (77.6% non-selective; 22.4% selective). Most frequently reported antimuscarinics were oxybutynin (56.3%) and solifenacin (21.4%). Multivariable analysis revealed that patients ≥75 years, of black race, and those with schizophrenia, epilepsy, delirium, and Elixhauser's score were less likely to initiate antimuscarinics. Women, those with abnormal involuntary movements, bipolar disorder, gastroesophageal reflux disease, insomnia, irritable bowel syndrome, muscle spasm/low back pain, neuropathic pain, benign prostatic hyperplasia, falls/fractures, myasthenia gravis, narrow-angle glaucoma, Parkinson's disease, syncope, urinary tract infection and vulvovaginitis were more likely to initiate antimuscarinics. Further, patients with muscle spasms/low back pain, benign prostatic hyperplasia and those taking higher level anticholinergics had lower odds of receiving non-selective antimuscarinics, whereas white patients, black patients and those with schizophrenia and delirium were more likely to receive them.ConclusionsNearly one-third of dementia patients had OAB and over one-fourth of them used antimuscarinics. Majority of the incident users were prescribed non-selective antimuscarinics with several demographic and clinical factors contributing to their use. Given the high prevalence of OAB among dementia patients, there is a need to optimize their antimuscarinic use, considering their vulnerability for anticholinergic adverse effects.

Dataset Information

Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial.

Publications

Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial.

Similar Datasets

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