Comparative Safety and Efficacy of Treatments for Overactive Bladder Among Older Adults: A Network Meta-analysis

Abstract

Background Cumulative exposure to one or more anticholinergic medications ("anticholinergic burden") is associated with an increased risk of adverse outcomes, particularly among older individuals. Mirabegron, an oral selective β3-adrenergic receptor agonist, has demonstrated efficacy in managing the symptoms of overactive bladder without contributing to anticholinergic burden. However, it is not known whether the favorable safety profile of mirabegron relative to antimuscarinics varies with increasing age among a patient population who may have a high anticholinergic burden. Objective The primary objective of this study was to indirectly compare the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with overactive bladder. Methods A systematic literature review was conducted to identify randomized controlled trials that reported safety and efficacy endpoints among patients aged ≥ 65 years. Identified randomized controlled trials were subsequently synthesized via a network meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in designing, performing, and reporting the literature review were followed. In line with current best practices, the network meta-analysis was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit. Estimates of relative safety were assessed via the odds ratio and estimates of relative efficacy were assessed via means and credible intervals. Results A total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria. Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis. Following review, five safety and five efficacy endpoints were considered for inclusion in the network meta-analysis. Regarding findings typical of anticholinergic exposure in older adults, mirabegron was not associated with an increased odds of dry mouth (odds ratio 95% credible interval 0.76 [0.26-2.37]) or constipation (1.08 [0.39-3.02]) relative to placebo, whereas antimuscarinics were strongly associated with these events (odds ratio range 3.78-7.85 and 2.12-4.66, respectively). In this older population, mirabegron was associated with a similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.99 [0.57-1.70]), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14-3.03 (in most cases, the association was mild). No increased odds of experiencing overall treatment-emergent adverse events was observed for mirabegron or antimuscarinics (odds ratio range 1.25-1.55), apart from fesoterodine (2.23 [1.37-3.37]). Finally, a similar treatment effect was observed across all efficacy endpoints between mirabegron and antimuscarinics in this older population. Conclusions This study indicates that the safety and effica...

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

“…Results for volume voided per micturition approached significance for the comparisons between vibegron and mirabegron and between vibegron and tolterodine. Our analysis provides long-term data for vibegron that has not been reported in previous network meta-analyses, which have included predominantly short-term trials of anticholinergics, 7 , 18 , 20 , 21 mirabegron 7 , 18 , 19 and onabotulinumtoxin A. 19 In general, these network meta-analyses of OAB treatments have shown similar short-term efficacy.…”

“…The long-term real-world efficacy of vibegron relative to other OAB treatments is not yet known; however, the 40-week EMPOWUR extension study, 17 which preserved randomization and double-blind treatment for patients receiving active treatment, provides an opportunity to compare long-term efficacy and safety of vibegron to other OAB treatments using data from extended-duration RCTs. Prior network meta-analyses have compared the efficacy of approved pharmacological treatments for OAB, 7 , 18 – 21 but few 19 , 20 have included trials with long-term (48- to 52-week) outcomes; to our knowledge, none have focused exclusively on the long-term outcomes or included vibegron 75 mg. This network meta-analysis compared the long-term (52-week) efficacy and safety of vibegron 75 mg with mirabegron (both β 3 –adrenergic agonists) and anticholinergic medications for OAB treatment.…”

Impact of Mirabegron Administration on the Blood Pressure and Pulse Rate in Patients with Overactive Bladder

“…Anticholinergic drugs are recognized as the standard treatment for OAB and are widely used. However, in some patients, anticholinergic drugs induce severe adverse events such as constipation, dry mouth, and cognitive dysfunction [7]. In addition, an excessive anticholinergic drug burden not only impairs the quality of life of patients due to adverse events but may also affect prognosis, particularly in elderly patients [17].…”

“…Although behavioral therapy is the basis of treatment for OAB, various guidelines recommend anticholinergic agents and β3 adrenergic receptor agonists following behavioral therapy [5,6]. Although they are effective for OAB, many researchers have reported adverse events with anticholinergic drugs, including constipation and dry mouth [7]. In addition, there are concerns about the effects of β3 adrenoreceptor agonists on the circulatory system, such as hypertension and tachycardia [8].…”

Clinical Utility of β3-Adrenoreceptor Agonists for the Treatment of Overactive Bladder: A Review of the Evidence and Current Recommendations

“… 44 These data were also supported by work of Lozano-Ortega et al who proved that mirabegron was similarly as effective as ACh across all efficacy end points in an older population. 45 …”