Efficacy and safety of combinations of mirabegron and solifenacin in patients with overactive bladder: a systematic review and meta-analysis

Deyi L1, Hong S2

Research Type


Abstract Category

Overactive Bladder

Abstract 307
E-Poster 2
Scientific Open Discussion ePoster Session 18
Thursday 5th September 2019
13:35 - 13:40 (ePoster Station 2)
Exhibition Hall
Overactive Bladder Urgency/Frequency Clinical Trial
1.west china hospital of sichuan unviersity, 2.west china hospital of sichuan unviersity

DeYi Luo



Hypothesis / aims of study
Antimuscarinics are the mainstay of oral pharmacotherapy for OAB, but persistence with treatment is limited by insufficient effectiveness and associated adverse events. Until now, the problem of treatment for OAB still remains challenging. Thus, the introduction of totally new drug mirabegron, which is a b3-adrenoreceptor agonist, has turned out to be much in demand among specialists engaged in OAB. In clinical practice, most OAB patients are initiated on an antimuscarinic, which is escalated to a higher dose or switched to an alternative antimuscarinic or the b3-adrenoceptor agonist, mirabegron. Some studies demonstrated that combination of mirabegron and antimuscarinic may improve efficacy without compromising tolerability, thus promoting treatment persistence. However, some studies found the adverse events were increased during use of combination therapy. Therefore, there is a clear need for a regularly updated and comprehensive systematic review of the effectiveness and safety of combination of mirabegron and solifenacin in comparison to solifenacin monotherapy in the management of OAB. This study was to investigate therapeutic efficacy enhancement capabilities of solifenacin and mirabegron combination in comparison to solifenacin monotherapy along with investigating the safety and tolerability of this combination.
Study design, materials and methods
We searched electronic databases including EMBASE, MEDLINE, and EBM Reviews to identify studies that explored the outcomes of combination therapy of solifenacin and mirabegron in overactive bladder (OAB). The meta-analysis was performed by Review Manager 5.3 software.The efficacy of combination therapy was assessed in improvements in the number of urgency episodes, MVV, the episodes of UI, micturition episodes, PPBC scores, total HRQoL scores and the number of patients with zero-incontinence. Safety endpoints included TEAEs like UTI, urinary retention (UR), dry mouth, constipation, and QT prolongation in ECG.
A total of 2411 articles were initially identified from the database and manual searches. 2137 papers are not RCTs. After deleting duplications, papers without mentioning study questions were excluded, 40 articles remain. After reviewing the full text of the remaining articles, literatures for different criterion of results, for different groups setting, and for animals were wiped out, eventually three RCTs involving 3038 patients were included in our analyses.In terms of efficacy, the results demonstrated that combination group presented significantly more mean volume voided (MVV) per micturition (MD=11.23; 95% CI: 7.21 to 15.25; P < 0.00001), less episodes of urgency incontinence (UI) (MD=-0.99; 95% CI: -1.17 to -0.80; P < 0.00001), less micturitions (MD=-0.45; 95% CI: -0.66 to -0.25; P < 0.0001), less urgency episodes (MD =-0.56;95% CI: -0.83 to-0.29; P < 0.0001), lower Patient Perception of Bladder Condition (PPBC) scores (MD=-0.49; 95% CI: -0.51 to -0.47; P < 0.00001), and more zero-incontinence (OR=1.44; 95% CI: 1.24 to 1.67; P < 0.00001), which overtly improved the total health-related quality of life (HRQoL) scores (MD=5.39; 95% CI: 3.38 to 7.41; P < 0.00001) for OAB patients. As for safety, there was no significant difference between the two groups in terms of treatment-emergent adverse events (TEAEs), such as dry mouth, urinary tract infection (UTI), urinary retention, and QT prolongation in electrocardiogram (ECG).
Interpretation of results
This meta-analysis was in an effort to identify whether solifenacin and mirabegron combination therapy enhances efficacy compared with solifenacin monotherapy, as well as to identify the safety and tolerability of this combination. Our results demonstrate that the combination group significantly improves the OAB symptoms of MVV per micturition, episodes of UI, micturition, and urgency episodes. This study also presents that combination therapy group showed significant decrease in PPBC scores, increases in number of responders for zero incontinence and total HRQoL score compared with solifenacin monotherapy. There was no significant difference between the two groups in terms of dry mouth, UR, UTI, and QT prolongation in ECG. In this study, we investigate the patient-reported outcomes (PROs), because the International Continence Society recommends the evaluation of PROs in OAB trials. Responder analyses represent an additional tool for translating changes in subjective or objective measures into a clinically meaningful binary outcome.
Concluding message
Combination therapy of solifenacin and mirabegron provides satisfactory therapeutic effect without increasing the risk of side effects, which undoubtedly improves quality of life of OAB patients. Combining mirabegron 50 mg with solifenacin 5 mg is a recommended dose due to the balance achieved between efficacy and acceptable tolerability.
Funding This study was supported by the National Natural Science Fund of China, Bio-engineer- ing bladder extracellular matrix remodeling re- gulated by the feedback circuit of mechano- responsive miRNA 3180-5p (81770673) and 1.3.5 project for disciplines of excellence, We- st China Hospital, Sichuan University (ZY- 2017310). Clinical Trial No Subjects None