Evaluating the efficacy and tolerability of mirabegron,a β3-adrenoceptor agonist,for the treatment of overactive bladder: Systematic review and network meta-analysis

Abstract

Purpose:

Overactive bladder (OAB) is a common condition affecting approximately 11% of individuals worldwide. One of the newest treatment options for OAB symptoms is mirabegron. The objective of this network meta-analysis is to evaluate the extent of the efficacy and tolerability of mirabegron compared both to placebo and first-line anticholinergic pharmacotherapies.

Methods:

Articles were identified through the MEDLINE, EMBASE, and Cochrane databases using the search term ‘mirabegron’. All original, prospective, randomised, controlled, double-blind clinical trials studying mirabegron in adults receiving initial treatment for OAB were included. Efficacy was assessed based on outcome variables and responder data. Tolerability was evaluated for reported adverse events.

Results:

Thirteen studies including a total of 13,333 individuals were included. Mirabegron demonstrated better efficacy compared to placebo and tolterodine extended release 4 mg. Compared to placebo, the incidence of tachycardia and nasopharyngitis was greater with mirabegron 50 mg, and the incidence of cardiac arrhythmia was greater in 100 mg treatment groups. Mirabegron 100 mg also demonstrated a lower incidence of cardiac arrhythmia compared to tolterodine.

Conclusions:

The current study presents new information that may affect patient-centred strategies for the management of OAB, with a particular concern for cardiovascular safety.

Keywords

Mirabegron β3 agonist overactive bladder lower urinary tract symptoms network meta-analysis

Get full access to this article

View all access options for this article.

References

Irwin

Kopp

Agatep

et al . Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int 2011; 108: 1132–1138.

Abrams

Cardozo

Fall

et al . The standardisation of terminology in lower urinary tract function: Report from the standardisation sub-committee of the International Continence Society. Urology 2003; 61: 37–49.

Coyne

Sexton

Irwin

et al . The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: Results from the EPIC study. BJU Int 2008; 101: 1388–1395.

Nambiar

Lucas

Chapter 4: Guidelines for the diagnosis and treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO). Neurourol Urodyn 2014; 33 (Suppl 3): S21–S25.

Maman

Aballea

Nazir

et al . Comparative efficacy and safety of medical treatments for the management of overactive bladder: A systematic literature review and mixed treatment comparison. Eur Urol 2014; 65: 755–765.

Andersson

Campeau

Olshansky

Cardiac effects of muscarinic receptor antagonists used for voiding dysfunction. Br J Clin Pharmacol 2011; 72: 186–196.

D’Souza

Smith

Miller

et al . Persistence, adherence, and switch rates among extended-release and immediate-release overactive bladder medications in a regional managed care plan. J Manag Care Pharm 2008; 14: 291–301.

Gormley

Lightner

Faraday

et al . Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol 2015; 193: 1572–1580.

Andersson

Martin

Nitti

Selective beta(3)-adrenoceptor agonists for the treatment of overactive bladder. J Urol 2013; 190: 1173–1180.

10.

Cui

Zong

Yang

et al . The efficacy and safety of mirabegron in treating OAB: A systematic review and meta-analysis of phase III trials. Int Urol Nephrol 2014; 46: 275–284.

11.

Chapple

Cardozo

Nitti

et al . Mirabegron in overactive bladder: A review of efficacy, safety, and tolerability. Neurourol Urodyn 2014; 33: 17–30.

12.

Thiagamoorthy

Kotes

Zacche

et al . The efficacy and tolerability of mirabegron, a beta3 adrenoceptor agonist, in patients with symptoms of overactive bladder. Ther Adv Urol 2016; 8: 38–46.

13.

Giarenis

Robinson

Cardozo

Overactive bladder and the beta3-adrenoceptor agonists: Current strategy and future prospects. Drugs 2015; 75: 1707–1713.

14.

Duan

Cao

et al . The role of mirabegron in overactive bladder: A systematic review and meta-analysis. Urol Int 2014; 93: 326–337.

15.

Song

Altman

Glenny

et al . Validity of indirect comparison for estimating efficacy of competing interventions: Empirical evidence from published meta-analyses. BMJ 2003; 326: 472.

16.

Abrams

Kelleher

Staskin

et al . Combination treatment with mirabegron and solifenacin in patients with overactive bladder: Efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony). Eur Urol 2015; 67: 577–588.

17.

Chapple

Dvorak

Radziszewski

et al . A phase II dose-ranging study of mirabegron in patients with overactive bladder. Int Urogynecol J 2013; 24: 1447–1458.

18.

Chapple

Amarenco

López Aramburu

et al . A proof-of-concept study: Mirabegron, a new therapy for overactive bladder. Neurourol Urodyn 2013; 32: 1116–1122.

19.

Chapple

Kaplan

Mitcheson

et al . Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a beta(3)-adrenoceptor agonist, in overactive bladder. Eur Urol 2013; 63: 296–305.

20.

Herschorn

Barkin

Castro-Diaz

et al . A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the beta(3) adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder. Urology 2013; 82: 313–320.

21.

Khullar

Amarenco

Angulo

et al . Efficacy and tolerability of mirabegron, a beta(3)-adrenoceptor agonist, in patients with overactive bladder: Results from a randomised European-Australian phase 3 trial. Eur Urol 2013; 63: 283–295.

22.

Kosilov

Loparev

Ivanovskaya

et al . A randomized, controlled trial of effectiveness and safety of management of OAB symptoms in elderly men and women with standard-dosed combination of solifenacin and mirabegron. Arch Gerontol Geriatr 2015; 61: 212–216.

23.

Kuo

Lee

et al . Results of a randomized, double-blind, parallel-group, placebo- and active-controlled, multicenter study of mirabegron, a beta3-adrenoceptor agonist, in patients with overactive bladder in Asia. Neurourol Urodyn 2015; 34: 685–692.

24.

Kuo

Lin

et al . Results of a randomized, double-blind, placebo-controlled study of mirabegron in a Taiwanese population with overactive bladder and comparison with other clinical trials. Urol Sci 2015; 26: 41–48.

25.

Nitti

Auerbach

Martin

et al . Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol 2013; 189: 1388–1395.

26.

Nitti

Rosenberg

Mitcheson

et al . Urodynamics and safety of the beta(3)-adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction. J Urol 2013; 190: 1320–1327.

27.

Yamaguchi

Marui

Kakizaki

et al . Phase III, randomised, double-blind, placebo-controlled study of the beta3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder. BJU Int 2014; 113: 951–960.

28.

Yamaguchi

Marui

Igawa

et al . Efficacy and safety of the selective beta3-adrenoceptor agonist mirabegron in Japanese patients with overactive bladder: A randomized, double-blind, placebo-controlled, dose-finding study. Low Urin Tract Symptoms 2015; 7: 84–92.

29.

Sacco

Bientinesi

Mirabegron: A review of recent data and its prospects in the management of overactive bladder. Ther Adv Urol 2012; 4: 315–324.

30.

Kuei

Peng

Liao

CH.

Perspectives on mirabegron in the treatment of overactive bladder syndrome: A new beta-3 adrenoceptor agonist. Urol Sci 2015; 26: 17–23.

31.

Bhide

Digesu

Fernando

et al . Mirabegron – a selective beta3-adrenoreceptor agonist for the treatment of overactive bladder. Res Rep Urol 2012; 4: 41–45.

32.

Habib

Reappraisal of the importance of heart rate as a risk factor for cardiovascular morbidity and mortality. Clin Ther 1997; 19 (Suppl A): 39–52.

33.

Andersson

Sarawate

Kahler

et al . Cardiovascular morbidity, heart rates and use of antimuscarinics in patients with overactive bladder. BJU Int 2010; 106: 268–274.

34.

Sears

Lewis

Noel

et al . Overactive bladder medication adherence when medication is free to patients. J Urol 2010; 183: 1077–1081.

35.

Wagg

Compion

Fahey

et al . Persistence with prescribed antimuscarinic therapy for overactive bladder: A UK experience. BJU Int 2012; 110: 1767–1774.

36.

Andersson

KE.

β3-receptor agonists for overactive bladder – new frontier or more of the same?

Curr Urol Rep 2013; 14: 435–441.

37.

Writing Group Members, Mozaffarian

Benjamin

et al . Heart disease and stroke statistics – 2016 update: A report from the American Heart Association. Circulation 2016; 133: e38–e360.

38.

Higgins

Thompson

Deeks

et al . Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.

39.

von Hippel

. The heterogeneity statistic I(2) can be biased in small meta-analyses. BMC Med Res Methodol 2015; 15: 35.

40.

Begg

Mazumdar

Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088–1101.

41.

Egger

Davey Smith

Schneider

et al . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

42.

Sterne

Gavaghan

Egger

Publication and related bias in meta-analysis: Power of statistical tests and prevalence in the literature. J Clin Epidemiol 2000; 53: 1119–1129.

43.

Otsuki

Kosaka

Nakamura

et al . β3-Adrenoceptor agonist mirabegron is effective for overactive bladder that is unresponsive to antimuscarinic treatment or is related to benign prostatic hyperplasia in men. Int Urol Nephrol 2013; 45: 53–60.