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 .
Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE).
BACKGROUND Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder ( OAB ) and is often difficult to treat with antimuscarinic monotherapy . OBJECTIVE To evaluate the efficacy and the safety and tolerability of combination ( solifenacin 5 mg and mirabegron 50 mg ) versus solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4 wk of solifenacin 5 mg . DESIGN , SETTING , AND PARTICIPANTS OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-wk single-blind run-in were r and omised 1:1:1 to double-blind daily combination or solifenacin 5 or 10 mg for 12 wk . Patients receiving the combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was a change from baseline to end of treatment ( EOT ) in the mean number of incontinence episodes per 24h ( stratified rank analysis of covariance [ ANCOVA ] ) . Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h ( ANCOVA ) and number of incontinence episodes noted in a 3-d diary at EOT ( mixed-effects Poisson regression ) . A trial ( BESIDE ) comparing combination treatment ( solifenacin plus mirabegron ) with one treatment alone ( solifenacin ) tested the superiority of combination versus solifenacin 5 mg , noninferiority ( and potential superiority ) of combination versus solifenacin 10 mg ( key secondary end points ) , and the safety and tolerability of combination therapy versus solifenacin monotherapy . RESULTS AND LIMITATIONS A total of 2174 patients were r and omised to combination ( n=727 ) , solifenacin 5 mg ( n=728 ) , or solifenacin 10 mg ( n=719 ) . At EOT , combination was superior to solifenacin 5 mg , with significant improvements in daily incontinence ( p=0.001 ) , daily micturitions ( p<0.001 ) , and incontinence noted in a 3-d diary ( p=0.014 ) . Combination was noninferior to solifenacin 10 mg for key secondary end points and superior to solifenacin 10 mg for improving daily micturitions . All treatments were well tolerated . CONCLUSIONS Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms versus solifenacin 5 or 10 mg , and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg . PATIENT SUMMARY In this 12-wk study , overactive bladder patients who remained incontinent despite initial solifenacin 5 mg treatment received additional treatment with mirabegron 50 mg . Combining mirabegron 50 mg with solifenacin 5 mg was superior to solifenacin 5 mg alone in improving symptoms of incontinence and frequent urination , and it was well tolerated . TRIAL REGISTRATION Clinical Trials.gov NCT01908829
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 .