Combination therapy studies of third-line treatments were rare and centered on medication with PTNS .
Combination therapy , with certain first , second , and third-line OAB therapies , appears to be efficacious .
AIMS Overactive bladder ( OAB ) affects over 17 % of the population and significantly effect the health-related quality of life .
The treatments for OAB include first line ( lifestyle modification , pelvic floor muscle training ) , second line ( anticholinergic or beta-3 agonist medications ) , and third line therapies ( intradetrusor botulinum toxin injection , sacral neurostimulation [ SNM ] , or percutaneous tibial nerve stimulation [ PTNS ] ) .
For those with urinary incontinence secondary to OAB , complete continence is the goal of therapy , though cure rates are only 5 % to 40 % .
The use of combination therapies can be employed in refractory OAB , however , the efficacy of pooled modalities is relatively unknown .
Our objective was to determine the volume of data supporting combination therapy in treating OAB .
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).
BACKGROUND Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic ( AM ) agent solifenacin may improve efficacy in the treatment of overactive bladder ( OAB ) while reducing the AM side effects . OBJECTIVE The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5 mg monotherapy . The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy . DESIGN , SETTING , AND PARTICIPANTS A phase 2 , factorial design , r and omised , double-blind , parallel-group , placebo- and monotherapy-controlled trial , conducted at 141 sites in 20 European countries . Male and female patients were aged ≥18 yr with symptoms of OAB for ≥3 mo . INTERVENTION A total of 1306 patients ( 66.4 % female ) were r and omised to 12 wk of treatment in 1 of 12 groups : 6 combination groups ( solifenacin 2.5 , 5 , or 10 mg plus mirabegron 25 or 50 mg ) , 5 monotherapy groups ( solifenacin 2.5 , 5 , or 10 mg , or mirabegron 25 or 50 mg ) , or placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Change from baseline to end of treatment in mean volume voided per micturition ( MVV ) ( primary end point ) and mean numbers of micturitions per 24 h , incontinence episodes per 24 h , and urgency episodes per 24 h were analysed using an analysis of covariance model . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , blood pressure , pulse rate , postvoid residual ( PVR ) volume , and laboratory and electrocardiography ( ECG ) parameters . RESULTS AND LIMITATIONS Compared with solifenacin 5 mg monotherapy , all combinations with solifenacin 5 or 10 mg significantly improved MVV , with adjusted differences ranging from 18.0 ml ( 95 % confidence interval [ CI ] , 5.4 - 30.0 ) to 26.3 ml ( 95 % CI , 12.0 - 41.0 ) . Three combination groups significantly reduced micturition frequency  compared with solifenacin 5 mg , ranging from -0.80 ( 95 % CI , -1.39 to -0.22 ) to -0.98 ( 95 % CI , -1.68 to -0.27 ) . Five of six combinations significantly reduced urgency episodes compared with solifenacin 5 mg , ranging from -0.98 ( 95 % CI , -1.78 , to -0.18 ) to -1.37 ( 95 % CI , -2.03 to -0.70 ) . No dose-related trends in TEAEs , blood pressure , pulse rate , PVR volume , or laboratory or ECG parameters were observed between combination and monotherapy groups , although the incidence of constipation was slightly increased with combination therapy . CONCLUSIONS Combination therapy with solifenacin/mirabegron significantly improved MVV , micturition frequency , and urgency compared with solifenacin 5 mg monotherapy . All combinations were well tolerated , with no important additional safety findings compared with monotherapy or placebo . PATIENT SUMMARY To improve treatment of overactive bladder ( OAB ) , mirabegron/solifenacin in combination was compared with each drug alone and placebo . Combination therapy improved OAB symptoms and had similar safety and acceptability . TRIAL REGISTRATION Clinical trials.gov : NCT01340027
Combination therapy studies of third-line treatments were rare and centered on medication with PTNS .
Combination therapy , with certain first , second , and third-line OAB therapies , appears to be efficacious .
AIMS Overactive bladder ( OAB ) affects over 17 % of the population and significantly effect the health-related quality of life .
The treatments for OAB include first line ( lifestyle modification , pelvic floor muscle training ) , second line ( anticholinergic or beta-3 agonist medications ) , and third line therapies ( intradetrusor botulinum toxin injection , sacral neurostimulation [ SNM ] , or percutaneous tibial nerve stimulation [ PTNS ] ) .
For those with urinary incontinence secondary to OAB , complete continence is the goal of therapy , though cure rates are only 5 % to 40 % .
The use of combination therapies can be employed in refractory OAB , however , the efficacy of pooled modalities is relatively unknown .
Our objective was to determine the volume of data supporting combination therapy in treating OAB .