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      Efficacy of Vibegron and Mirabegron for Overactive Bladder: A Systematic Literature Review and Indirect Treatment Comparison

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          Abstract

          Background

          In the absence of head-to-head trials, we performed an indirect treatment comparison of the β 3-adrenergic agonists vibegron and mirabegron in the treatment of overactive bladder (OAB).

          Methods

          PubMed, Embase, and Cochrane Library were searched for articles related to phase 3, double-blind, controlled trials of vibegron 75 mg and mirabegron 25/50 mg in patients with OAB. Efficacy outcomes included change from baseline at weeks 4, 12, and 52 in mean daily number of total urinary incontinence episodes and micturitions and mean volume voided/micturition. Effect size was computed as placebo-subtracted change from baseline (weeks 4, 12) or active control (tolterodine)-subtracted change from baseline (week 52) for each treatment group. Adverse events (AEs) are presented descriptively.

          Results

          After removal of duplicates, 49 records were identified, and after screening 9 met inclusion criteria for analysis. Vibegron showed significantly greater reduction in mean daily number of total incontinence episodes than mirabegron 25 mg at week 4, mirabegron 50 mg (weeks 4, 52), and tolterodine (weeks 4, 12) ( P < 0.05, each) and significantly greater improvement in volume voided versus mirabegron 25 mg (week 12), mirabegron 50 mg (weeks 12, 52), and tolterodine (week 4) ( P < 0.05, each). Confidence intervals of point estimates overlapped zero for all other comparisons of vibegron and mirabegron (25 or 50 mg) or tolterodine, indicating no significant differences between treatments for these time/endpoints. Urinary tract infection, hypertension, and dry mouth were the most commonly occurring AEs for vibegron, mirabegron, and tolterodine, respectively, in the short-term trials; hypertension was the most commonly occurring AE with all three treatments in the long-term trials.

          Conclusions

          Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks. Improvement in micturitions was similar between vibegron and mirabegron or tolterodine. Incidence of AEs was generally comparable between vibegron and mirabegron.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s12325-021-01902-8.

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          Most cited references24

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          A Nonparametric “Trim and Fill” Method of Accounting for Publication Bias in Meta-Analysis

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            The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials

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              Patient-reported reasons for discontinuing overactive bladder medication.

              To evaluate patient-reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB). A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase-2 follow-up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow-up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre-coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo-Mendell-Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment. In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo-Mendell-Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment. Expectations about treatment efficacy and side-effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side-effects might enhance adherence.
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                Author and article information

                Contributors
                Michael.Kennelly@atriumhealth.org
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Cheshire )
                0741-238X
                1865-8652
                18 September 2021
                18 September 2021
                2021
                : 38
                : 11
                : 5452-5464
                Affiliations
                [1 ]GRID grid.239494.1, ISNI 0000 0000 9553 6721, Department of Urology, Obstetrics and Gynecology, , Carolinas Medical Center, ; 2001 Vail Ave, Suite 360, Charlotte, NC 28207 USA
                [2 ]CERobs Consulting, LLC, Chapel Hill, NC USA
                [3 ]Urovant Sciences, Irvine, CA USA
                Author information
                http://orcid.org/0000-0002-7044-506X
                Article
                1902
                10.1007/s12325-021-01902-8
                8520873
                34537953
                c8089448-3f6a-4895-a1cb-0aa62a4094ce
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 6 July 2021
                : 24 August 2021
                Funding
                Funded by: Urovant Sciences
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare Ltd., part of Springer Nature 2021

                adrenergic agonists,urinary bladder,overactive,urinary incontinence

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