PMID- 31416636
OWN - NLM
STAT- MEDLINE
DCOM- 20201217
LR  - 20201217
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Linking)
VI  - 76
IP  - 6
DP  - 2019 Dec
TI  - Efficacy and Safety of Combination Pharmacotherapy for Patients with Overactive 
      Bladder: A Rapid Evidence Assessment.
PG  - 767-779
LID - S0302-2838(19)30534-2 [pii]
LID - 10.1016/j.eururo.2019.07.010 [doi]
AB  - CONTEXT: Oral pharmacotherapy consisting of antimuscarinics, beta3-adrenoreceptor 
      agonists, or combinations of these agents forms the mainstay of overactive 
      bladder (OAB) management. OBJECTIVE: To evaluate the efficacy and safety of 
      combination therapy in patients with OAB. EVIDENCE ACQUISITION: A literature 
      search was conducted in June 2018 using Embase, MEDLINE, and Cochrane databases 
      via Ovid and relevant congress abstracts. Studies reporting the efficacy/safety 
      of two antimuscarinics or a beta3-adrenoreceptor agonist plus an antimuscarinic were 
      included. EVIDENCE SYNTHESIS: Publications reported on clinical efficacy, safety, 
      and health-related quality of life (HRQoL) for mirabegron (M) plus solifenacin 
      (S) from three 12-wk randomised controlled trials (RCTs)-SYMPHONY, SYNERGY, and 
      BESIDE-and a 12-mo RCT, SYNERGY II. SYMPHONY reported statistically significant 
      improvements in clinical symptoms and HRQoL with combination therapy versus 
      solifenacin 5 mg (S5) and placebo. In SYNERGY, there were consistent improvements 
      in urinary incontinence (UI) episodes/24 h and micturitions/24 h (coprimary 
      endpoints), and in secondary efficacy parameters with mirabegron 25 mg (M25) + S5 
      and mirabegron 50 mg (M50) + S5 versus respective monotherapies. In patients with 
      an inadequate response to S5 monotherapy (BESIDE), greater improvements in UI 
      (primary endpoint) were noted for M50 + S5 versus S5 (p = 0.001). Combination 
      therapy was noninferior to solifenacin 10 mg (S10) for reduction in UI and 
      superior to S10 for improvement in micturition frequency (p < 0.001), and 
      resulted in greater improvements from baseline in OAB-5 Dimension scores versus 
      S5 and S10 (p < 0.01). In SYNERGY II, clinically meaningful and sustained 
      improvements in clinical outcomes were observed for M50 + S5 versus M50 or S5. 
      Combination therapy was well tolerated in all four trials. The incidence of 
      adverse events (AEs) was similar across groups, and there were no notable 
      differences in the incidence of specific AEs. Positive efficacy outcomes were 
      observed in five studies of dual antimuscarinic therapy (trospium + solifenacin). 
      CONCLUSIONS: Mirabegron plus solifenacin provides effective, well-tolerated 
      treatment for patients with OAB. Limited data for dual antimuscarinic therapy 
      suggest a benefit in patients with moderate-to-severe symptoms. PATIENT SUMMARY: 
      Overactive bladder (OAB) is treated with medicines called antimuscarinics, such 
      as solifenacin, propiverine, or trospium, or another beta-adrenoreceptor agonist 
      medicine called mirabegron, which works in a different way. We looked at 
      published scientific studies of patients with OAB treated with mirabegron plus 
      solifenacin together, or with two antimuscarinics. We found that mirabegron plus 
      solifenacin can help reduce symptoms and improve quality of life. Patients 
      tolerate this treatment well, with few patients experiencing side effects.
CI  - Copyright (c) 2019. Published by Elsevier B.V.
FAU - Gratzke, Christian
AU  - Gratzke C
AD  - Department of Urology, University Hospital Freiburg, Freiburg, Germany. 
      Electronic address: christian.gratzke@uniklinik-freiburg.de.
FAU - Chapple, Christopher
AU  - Chapple C
AD  - Royal Hallamshire Hospital, Department of Urology, Sheffield Teaching Hospitals 
      NHS Trust, Sheffield, UK.
FAU - Mueller, Elizabeth R
AU  - Mueller ER
AD  - Loyola University Chicago Stritch School of Medicine, Division of Female Pelvic 
      Medicine and Reconstructive Surgery, Maywood, IL, USA.
FAU - Robinson, Dudley
AU  - Robinson D
AD  - King's College Hospital, Department of Urogynaecology, London, UK.
FAU - Rolland, Catherine
AU  - Rolland C
AD  - Envision Pharma Group, Curo, Horsham, UK.
FAU - Staskin, David
AU  - Staskin D
AD  - St Elizabeth's Medical Center, Division of Urology, Boston, MA, USA.
FAU - Stoelzel, Matthias
AU  - Stoelzel M
AD  - Astellas Pharma, Astellas Pharma Global Development, Leiden, The Netherlands.
FAU - Maanen, Rob van
AU  - Maanen RV
AD  - Astellas Pharma, Astellas Pharma Global Development, Leiden, The Netherlands.
FAU - Siddiqui, Emad
AU  - Siddiqui E
AD  - Astellas Pharma, Astellas Pharma Global Development, Chertsey, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190813
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Adrenergic beta-3 Receptor Agonists)
RN  - 0 (Muscarinic Antagonists)
SB  - IM
CIN - Eur Urol. 2019 Dec;76(6):780-781. PMID: 31540792
CIN - J Urol. 2020 Dec;204(6):1388-1389. PMID: 33052782
MH  - Adrenergic beta-3 Receptor Agonists/adverse effects/*therapeutic use
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Muscarinic Antagonists/adverse effects/*therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
MH  - Urinary Bladder, Overactive/*drug therapy
OTO - NOTNLM
OT  - Antimuscarinics
OT  - Combination therapy
OT  - Health-related quality of life
OT  - Mirabegron
OT  - Overactive bladder
OT  - Solifenacin
OT  - Symptoms
EDAT- 2019/08/17 06:00
MHDA- 2020/12/18 06:00
CRDT- 2019/08/17 06:00
PHST- 2019/03/13 00:00 [received]
PHST- 2019/07/05 00:00 [accepted]
PHST- 2019/08/17 06:00 [pubmed]
PHST- 2020/12/18 06:00 [medline]
PHST- 2019/08/17 06:00 [entrez]
AID - S0302-2838(19)30534-2 [pii]
AID - 10.1016/j.eururo.2019.07.010 [doi]
PST - ppublish
SO  - Eur Urol. 2019 Dec;76(6):767-779. doi: 10.1016/j.eururo.2019.07.010. Epub 2019 
      Aug 13.