Efficacy and Tolerability of Mirabegron Compared with Antimuscarinic Monotherapy or Combination Therapies for Overactive Bladder: A Systematic Review and Network Meta-analysis

Background: Mirabegron is an established treatment alternative to antimuscarinic therapy for patients with overactive bladder (OAB), as shown by efficacy and tolerability data from phase III trials. Objective: To assess efficacy and tolerability of mirabegron 50 mg versus antimuscarinic monotherapies and combination therapies. Design, setting, and participants: Systematic literature review and network meta-analysis of randomised controlled trials (2000-2017) assessing eligible treatments for OAB. Outcome measurements and statistical analysis: Efficacy assessments included micturition frequency, urgency urinary incontinence, dry rate, and 50% reduction in incontinence. Tolerability assessments included dry mouth, constipation, blurred vision, and hypertension. Results and limitations: A total of 64 studies (n = 46 666) were included in the network meta-analysis. Mirabegron 50 mgwas significantly more efficacious than placebo for all efficacy endpoints. Comparable overall efficacy was observed for mirabegron 50 mg versus most active treatments, but solifenacin 10 mg monotherapy and solifenacin 5 mg plus mirabegron 25 or 50 mg in combination were more efficacious for some/all outcomes. Mirabegron 50 mg was significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators, respectively; similar overall tolerability was observed between mirabegron 50 mg and all treatments (including placebo) for the remaining endpoints. Limitations of the study included between-trial variations in the definition of certain endpoints and heterogeneity of the available data (eg, number of studies and patients assessed) for comparator treatments across different endpoints. Conclusions: The relief of key OAB symptoms produced by mirabegron 50 mg is significantly better than placebo, and similar to a range of common antimuscarinics, with the benefit of significantly fewer bothersome anticholinergic side effects such as dry mouth. Combination treatment of solifenacin 5 mg plus mirabegron 25 or 50 mg appears to provide an efficacy benefit compared with mirabegron 50 mg, with the expected side effects of individual antimuscarinics. Patient summary: This study assessed the efficacy and tolerability of different drug treatments for OAB. Mirabegron 50 mgwas as effective as antimuscarinic therapy, with fewer common, bothersome side effects such as dry mouth, constipation, and urinary retention. Combination treatment of solifenacin 5 mg plus mirabegron 25 or 50 mg was more effective than mirabegron 50 mg alone, but with more anticholinergic side effects. (C) 2018 European Association of Urology. Published by Elsevier B.V.