title: OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Efficacy of botulinum toxin-A for treating idiopathic detrusor overactivity: results from a single center, randomized, double-blind, placebo controlled trial. OnabotulinumtoxinA 100U provides significant improvements in overactive bladder symptoms in patients with urinary incontinence regardless of the number of anticholinergic therapies used or reason for inadequate management of overactive bladder Long-term efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: an interim analysis. OnabotulinumtoxinA is Effective in Patients with Urinary Incontinence due to Neurogenic Detrusor Activity Regardless of Concomitant Anticholinergic Use or Neurologic Etiology Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. Efficacy and safety of low doses of onabotulinumtoxinA for the treatment of refractory idiopathic overactive bladder: a multicentre, double-blind, randomised, placebo-controlled dose-ranging study. Outcome of a randomized, double-blind, placebo controlled trial of botulinum A toxin for refractory overactive bladder. OnabotulinumtoxinA improves quality of life in patients with neurogenic detrusor overactivity OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. The effect of botulinum-A toxin on patients with severe urge urinary incontinence. Clinical effects of suburothelial injection of botulinum A toxin on patients with nonneurogenic detrusor overactivity refractory to anticholinergics. A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin. A prospective study to evaluate the safety, tolerability, efficacy and durability of response of intravesical injection of botulinum toxin type A into detrusor muscle in patients with refractory idiopathic detrusor overactivity Efficacy of botulinum toxin type A 100 units versus 200 units for treatment of refractory idiopathic overactive bladder Sacral neuromodulation for the treatment of neurogenic lower urinary tract dysfunction caused by multiple sclerosis: a single-centre prospective series Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. Botulinum-A toxin detrusor and sphincter injection in treatment of overactive bladder syndrome: objective outcome and patient satisfaction. Exploring the impact of changes in neurogenic urinary incontinence frequency and condition-specific quality of life on preference-based outcomes Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. Botulinum A toxin injections into the detrusor: an effective treatment in idiopathic and neurogenic detrusor overactivity? Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics. Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder.
abstract: BACKGROUND Overactive bladder ( OAB ) syndrome with urinary incontinence ( UI ) is prevalent in the population and impairs health-related quality of life ( HRQOL ) . OBJECTIVE To assess the impact on efficacy , safety , and HRQOL of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) treatment in patients with OAB with UI . DESIGN , SETTING , AND PARTICIPANTS This pivotal , multicentre , double-blind , r and omised , placebo-controlled , phase 3 study enrolled patients with idiopathic OAB with ≥ 3 urgency UI episodes over 3 d and ≥ 8 micturitions per day who were inadequately managed by anticholinergics . INTERVENTION OnabotulinumtoxinA at a 100U dose ( n=277 ) or placebo ( n=271 ) , administered as 20 intradetrusor injections of 0.5 ml . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Co- primary end points were change from baseline in the number of UI episodes per day and proportion of patients reporting positive treatment response on the treatment benefit scale ( TBS ) at week 12 . Additional end points included other OAB symptoms ( episodes of urinary urgency incontinence , micturition , urgency , and nocturia ) and HRQOL ( Incontinence Quality of Life [ I-QOL ] , King 's Health Question naire [ KHQ ] ) . Safety assessment s included adverse events ( AEs ) , postvoid residual ( PVR ) urine volume , and initiation of clean intermittent catheterisation ( CIC ) . RESULTS AND LIMITATIONS OnabotulinumtoxinA significantly decreased UI episodes per day at week 12 ( -2.95 for onabotulinumtoxinA versus -1.03 for placebo ; p<0.001 ) . Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinumtoxinA compared with placebo ( p ≤ 0.01 ) . Patients perceived a significant improvement in their condition , as measured by patients with a positive treatment response on the TBS ( 62.8 % for onabotulinumtoxinA versus 26.8 % for placebo ; p<0.001 ) . Clinical ly meaningful improvements from baseline in all I-QOL and KHQ multi-item domains ( p<0.001 versus placebo ) indicated positive impact on HRQOL . AEs were mainly localised to the urinary tract . Mean PVR was higher in the onabotulinumtoxinA group ( 46.9 ml versus 10.1 ml at week 2 ; p<0.001 ) ; 6.9 % of onabotulinumtoxinA patients versus 0.7 % of placebo patients initiated CIC . CONCLUSIONS OnabotulinumtoxinA 100 U was well tolerated and demonstrated significant and clinical ly relevant improvements in all OAB symptoms , patient-reported benefit , and HRQOL in patients inadequately managed by anticholinergics . TRIAL REGISTRATION Clinical Trials.gov : NCT00910520 PURPOSE We evaluated the use of botulinum toxin-A in treating patients with idiopathic detrusor overactivity refractory to anticholinergics . MATERIAL S AND METHODS This double-blind , placebo controlled trial r and omized participants to intradetrusor injections of 200 U botulinum toxin-A ( 16 patients ) or placebo ( 18 patients ) . The primary outcome measure was change in maximum cystometric capacity . Secondary outcome measures included changes in overactive bladder symptoms , post-void residual , maximum detrusor pressure during filling cystometry and reflex detrusor volume . Quality of life was assessed using the Incontinence Impact Question naire short form 7 and Urogenital Distress Inventory short form 6 . Followup occurred at 4 and 12 weeks after injection , at which point the study was unblinded . Further followup in the botulinum toxin-A group occurred at 24 weeks . RESULTS Significant increases in maximum cystometric capacity were observed at 4 weeks ( difference 144.69 ml , 95 % CI 100.95 to 215.75 , p < 0.0001 ) and 12 weeks ( difference 95.71 ml , 95 % CI 47.47 to 172.45 , p = 0.001 ) in patients treated with botulinum toxin-A compared to placebo . Botulinum toxin-A reduced frequency ( p < 0.001 , p = 0.003 ) and urgency urinary incontinence ( p = 0.03 , p = 0.008 ) episodes at 4 and 12 weeks , respectively . Urgency was reduced at 4 weeks ( p = 0.005 ) in the botulinum toxin-A group . In patients receiving botulinum toxin-A , post-void residual increased at 4 weeks ( p = 0.024 ) but became insignificant by 12 weeks ( p = 0.406 ) . Of these patients 6 required intermittent self-catheterization . Significant improvements in quality of life were observed following botulinum toxin-A. The extension study suggests that the beneficial effects of botulinum toxin-A are maintained for at least 24 weeks . CONCLUSIONS Botulinum toxin-A at 200 U is safe and effective for idiopathic detrusor overactivity and the beneficial effects persist for at least 24 weeks Introduction A prespecified pooled analysis of two placebo-controlled , phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder ( OAB ) patients with urinary incontinence ( UI ) . Methods Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo , sparing the trigone . Change from baseline at week 12 in UI episodes/day , proportion of patients reporting a positive response ( ‘ greatly improved ’ or ‘ improved ’ ) on the treatment benefit scale ( TBS ) , micturition and urgency were evaluated by number of prior anticholinergics ( 1 , 2 or ≥ 3 ) and reason for their discontinuation ( insufficient efficacy or side effects ) . Adverse events ( AE ) were assessed . Results Patients had taken an average of 2.4 anticholinergics before study enrolment . OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo , regardless of the number of prior anticholinergics ( −2.82 vs. −1.52 for one prior anticholinergic ; −2.58 vs. −0.58 for two prior anticholinergics ; and −2.92 vs. −0.73 for three or more prior anticholinergics ; all p < 0.001 ) . The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo ( 69.0 % vs. 37.2 % for one prior anticholinergic ; 58.8 % vs. 24.8 % for two prior anticholinergics and 56.4 % vs. 22.5 % for three or more prior anticholinergics ; all p < 0.001 ) . Similar results were observed regardless of the reason for discontinuation . OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups . AEs were well tolerated , with a comparable incidence in all groups . Conclusion In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics , onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB . Clinical Trials.gov : NCT00910845 , NCT00910520 OBJECTIVE To evaluate the long-term efficacy and safety of repeat onabotulinumtoxinA injections in patients inadequately managed by anticholinergics for urinary incontinence ( UI ) due to neurogenic detrusor overactivity . MATERIAL S AND METHODS Patients who completed either of 2 preceding phase III studies were offered entry into an extension study and received repeat onabotulinumtoxinA 200 U or 300 U. The data were integrated across the phase III and ongoing extension studies . The present interim analysis included all patients who received ≥ 1 onabotulinumtoxinA treatment . The data were analyzed by treatment cycle ( cycles 1 - 5 ) . The primary assessment was the change from baseline in UI episodes/wk at 6 weeks after each treatment . Additional assessment s included ≥ 50 % and 100 % reductions in UI episodes , volume/void , Incontinence Quality of Life responses , and adverse events . RESULTS A total of 387 , 336 , 241 , 113 , and 46 patients received 1 , 2 , 3 , 4 , and 5 onabotulinumtoxinA treatments , respectively . The UI episodes/wk were consistently reduced compared with baseline after repeated onabotulinumtoxinA treatment ( -22.7 , -23.3 , -23.1 , -25.3 , and -31.9 for the 200-U onabotulinumtoxinA group in cycles 1 - 5 ) . The proportion of patients reporting ≥ 50 % and 100 % ( " dry " ) reductions from baseline in UI episodes at week 6 ranged from 73%-94 % and 36%-55 % , respectively . Increases in the mean volume/void ( mean increase > 130 mL ) and improvements in quality of life were also observed after repeat treatment . The most common adverse events were urinary tract infections and urinary retention , with no change in the adverse event profile over time . CONCLUSION The results of our study have shown that repeated onabotulinumtoxinA treatments provide sustained reductions in UI episodes and increases in the volume/void and quality of life in patients with neurogenic detrusor overactivity and UI who were inadequately managed by anticholinergics , with no new safety signals Introduction To evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity ( NDO ) in sub population s of etiology ( multiple sclerosis [ MS ] or spinal cord injury [ SCI ] ) and concomitant anticholinergics ( use/non-use ) . Methods Data were pooled from two double-blind , placebo-controlled , pivotal , phase 3 studies including a total of 691 patients with ≥14 urinary incontinence ( UI ) episodes/week due to MS ( n = 381 ) or SCI ( n = 310 ) . Patients received intradetrusor injections of onabotulinumtoxinA 200U ( n = 227 ) , 300U ( n = 223 ) , or placebo ( n = 241 ) . Change from baseline at week 6 in UI episodes/week ( primary endpoint ) , urodynamics , quality of life ( QOL ) , and adverse events ( AEs ) were assessed . Results Significant and similar reductions in UI episodes were observed regardless of etiology or anticholinergic use : at week 6 , mean weekly decreases of −22.6 and −19.6 were seen in MS and SCI patients , respectively , and −20.3 and −22.5 in anticholinergic users and non-users , respectively , treated with onabotulinumtoxinA 200U . The 300U dose did not add to the clinical efficacy in any sub population . Similar proportions of patients achieved ≥50 % or 100 % reductions in UI episodes in all subgroups . Improvements in maximum cystometric capacity , maximum detrusor pressure during first involuntary detrusor contraction , and QOL were significant in both etiologies and were independent of anticholinergic use . The most common AEs in all groups were urinary tract infection and urinary retention . Conclusion Regardless of concomitant anticholinergic use or etiology , onabotulinumtoxinA significantly improved UI symptoms , urodynamics , and QOL  in patients with UI due to NDO . OnabotulinumtoxinA was well tolerated in all groups PURPOSE We determined the safety and efficacy of each of 2 doses of botulinum toxin type A ( BTX-A ) ( 200 or 300 U BOTOX ) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin . MATERIAL S AND METHODS A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity ( due to spinal cord injury in 53 and multiple sclerosis in 6 ) requiring clean intermittent self-catheterization were r and omized to receive a single dose into the detrusor of BTX-A ( 200 U or 300 U ) or placebo . Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks . Key urodynamic assessment s ( maximum cystometric capacity , reflex detrusor volume and maximum detrusor pressure during bladder contraction ) were used to provide objective measures of the treatment effect on bladder function . The impact of treatment on quality of life was assessed using the Incontinence Quality of Life question naire . RESULTS There were significant posttreatment decreases in incontinence episodes from baseline in the 2 BTX-A groups ( p < /=0.05 ) but not in the placebo group . In addition , more patients who received BTX-A reported no incontinence episodes during at least 1 posttreatment evaluation period . Positive treatment effects were also reflected by significant improvements in bladder function in the BTX-A groups , as assessed by urodynamics and in patient quality of life . Benefits were observed from the first evaluation at week 2 to the end of the 24-week study . No safety concerns were raised . CONCLUSIONS Intramuscular injections of BTX-A into the detrusor can provide rapid , well tolerated , clinical ly significant decreases in the signs and symptoms of urinary incontinence caused by neurogenic detrusor overactivity during a 24-week study period BACKGROUND In the treatment of patients with idiopathic overactive bladder ( iOAB ) , high doses of botulinum toxin type A ( BoNTA ) were often associated with complications result ing from high postvoid residuals ( PVR ) , leading to clean intermittent catheterisation ( CIC ) and urinary tract infections ( UTI ) . OBJECTIVE Evaluate the efficacy and tolerability of low doses of onabotulinumtoxinA compared to placebo in patients with iOAB . DESIGN , SETTING , AND PARTICIPANTS Between 2005 and 2009 , adults with persistent iOAB were included in a prospect i ve , r and omised , double-blind , placebo-controlled comparative trial . INTERVENTION Patients were r and omised to undergo a single intradetrusor injection procedure of either placebo or onabotulinumtoxinA ( 50 U , 100 U or 150 U ) . MEASUREMENTS The initial evaluations ( ie , clinical and urodynamic variables as well as quality of life [ QoL ] ) were repeated at day 8 and months 1 , 3 , 5 , and 6 . RESULTS AND LIMITATIONS Ninety-nine patients were included in the efficacy analysis . Three months after the procedure , we observed>50 % improvement versus baseline in urgency and urge urinary incontinence ( UUI ) in 65 % and 56 % of patients who respectively received 100 U ( p=0.086 ) and 150 U ( p=0.261 ) BoNTA injections and > 75 % improvement in 40 % of patients of both groups ( 100 U [ p=0.058 ] and 150 U [ p=0.022 ] ) . Complete continence was observed in 55 % and 50 % patients after 100 U and 150 U BoNTA treatment , respectively , at month 3 . Frequency symptoms and QoL improved up to the 6-mo visit . We observed only three patients with a PVR>200 ml in the 150 U group and a few UTIs . CONCLUSIONS 100 U and 150 U BoNTA injections were well tolerated and have both shown to improve symptoms and QoL in patients with iOAB . Nevertheless , 100 U injections showed a reasonable efficacy , with a lower risk of high PVR . TRIAL REGISTRATION Clinical Trials.gov NCT00231491 PURPOSE We determined the effectiveness of cystoscopic administration of botulinum-A toxin compared to placebo for the treatment of urinary incontinence in subjects with idiopathic overactive bladder . MATERIAL S AND METHODS Subjects were recruited from the Division of Urogynecology at the University of Rochester . Inclusion criteria were overactive bladder refractory to anticholinergic medications , multiple daily incontinence episodes and a 24-hour pad weight of 100 gm or greater . Subjects with low leak point pressures , increased post-void residual volume or neurological etiologies were excluded from study . Subjects were r and omized to placebo or to 1 of 2 doses of botulinum-A toxin . The detrusor was injected at 8 to 10 sites above the trigone . Evaluations were performed at baseline , and at 3 and 6 weeks after injection , and included bladder diaries , pad weights , quality of life question naires and urodynamic studies . RESULTS A total of 22 subjects participated in stage 1 of this 2-stage study . We report on the outcomes of stage 1 of this study . Because stage 2 is still ongoing and investigators remain blind to the doses of botulinum-A toxin , the 2 botulinum-A toxin groups were combined for this report . There were no differences in mean baseline measurements between the 2 groups . Statistically significant improvements in daily incontinence episodes , pads changed per day and quality of life question naires were seen in the botulinum-A toxin group with no changes in the placebo group . No change in nocturia , daily voiding frequency , peak flow or detrusor pressure was seen in either group . Of 15 subjects 4 ( 26 % ) receiving botulinum-A toxin had a post-void residual volume of 200 cc or greater and 1 subject required intermittent catheterization . Four subjects experienced a urinary tract infection , 2 ( 13 % ) in the botulinum-A toxin group and 2 ( 28 % ) in the placebo group ( not significant ) . CONCLUSIONS Botulinum-A toxin can significantly reduce urge urinary incontinence due to overactive bladder at 6 weeks . However , there is a risk of urinary retention requiring self-catheterization Objective : To evaluate the effects of onabotulinumtoxinA on patient-reported outcomes including health-related quality of life ( HRQOL ) , treatment satisfaction , and treatment goal attainment in patients with urinary incontinence ( UI ) due to neurogenic detrusor overactivity ( NDO ) . Methods : In this multicenter , double-blind , r and omized , placebo-controlled , phase III , 52-week study ( Clinical Trials.gov NCT00311376 ) , patients with UI due to NDO who were not adequately managed with anticholinergic therapy were treated with intradetrusor injections of onabotulinumtoxinA ( 200 or 300 U ) or placebo ( 0.9 % saline ) . HRQOL measures included the Incontinence Quality of Life ( I-QOL ) Question naire total score , and the 3 domain scores ( avoidance and limiting behavior , psychosocial , and social embarrassment ) , the modified Overactive Bladder Patient Satisfaction with Treatment Question naire ( OAB-PSTQ ) , and Patient Global Assessment . Assessment s were made at baseline , posttreatment week 6 ( primary time point ) , week 12 , and at 12-week intervals . Results : Patients ( mean age of 46 years with 30.5 weekly UI episodes at baseline ) were r and omized to receive placebo ( n = 149 ) or onabotulinumtoxinA ( 200 U [ n = 135 ] or 300 U [ n = 132 ] ) . At week 6 , improvements from baseline in I-QOL Question naire total score were greater ( p < 0.001 ) in both onabotulinumtoxinA-treated groups vs placebo . Responses to the OAB-PSTQ also demonstrated greater mean improvements from baseline ( p < 0.001 ) in both onabotulinumtoxinA-treated groups vs placebo at week 6 . Patients who received onabotulinumtoxinA also reported greater improvement in the Patient Global Assessment than those in the placebo group ( p ≤ 0.001 vs placebo ) . Conclusions : Patients with UI due to NDO reported greater improvement in HRQOL and treatment satisfaction with onabotulinumtoxinA than with placebo consistently across several patient-reported outcome instruments . Classification of evidence : This study provides Class I evidence that onabotulinumtoxinA intradetrusor injections ( 200 or 300 U ) can improve quality of life measures in patients with NDO not adequately managed with anticholinergic therapy PURPOSE Overactive bladder affects 12 % to 17 % of the general population and almost a third experience urinary incontinence , which may severely impact health related quality of life . Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects , leading to a high discontinuation rate . We report the results of the first large ( 557 patients ) , phase 3 , placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics . MATERIAL S AND METHODS Eligible patients with overactive bladder , 3 or more urgency urinary incontinence episodes in 3 days and 8 or more micturitions per day were r and omized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100 U or placebo . Co- primary end points were the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a positive response on the treatment benefit scale at posttreatment week 12 . Secondary end points included other overactive bladder symptoms and health related quality of life . Adverse events were assessed . RESULTS OnabotulinumtoxinA significantly decreased the daily frequency of urinary incontinence episodes vs placebo ( -2.65 vs -0.87 , p < 0.001 ) and 22.9 % vs 6.5 % of patients became completely continent . A larger proportion of onabotulinumtoxinA than placebo treated patients reported a positive response on the treatment benefit scale ( 60.8 % vs 29.2 % , p < 0.001 ) . All other overactive bladder symptoms improved vs placebo ( p ≤ 0.05 ) . OnabotulinumtoxinA improved patient health related quality of life across multiple measures ( p < 0.001 ) . Uncomplicated urinary tract infection was the most common adverse event . A 5.4 % rate of urinary retention was observed . CONCLUSIONS OnabotulinumtoxinA 100 U showed significant , clinical ly relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated PURPOSE We determined the effect of 150 units of botulinum-A toxin ( Botox , Allergan , Irvine , California ) on subjects with severe urge urinary incontinence ( UUI ) . MATERIAL S AND METHODS This was an open label uncontrolled clinical trial . Subjects were recruited from the female urology and urogynecology clinics at Duke University . Inclusion criteria included evidence of UUI on 3-day bladder diary , a 24-hour pad weight of 100 gm or greater , absent or minimal stress leakage , absent detrusor dysfunction , and a history of failed anticholinergic and physical therapies . Exclusion criteria included evidence of a urinary tract infection , or other correctable or neurological etiology for UUI . The detrusor of each subject was injected with 150 units of botulinum-A toxin . Evaluations were performed at 2 weeks , 6 weeks , 3 months and 6 months after injection . Outcome measures included daily incontinence episodes , Urogenital Distress Inventory and the Incontinence Impact Question naire , 24-hour pad weights , daily pad usage and urinalysis at all visits . Urodynamic studies were performed at the 6-week and 3-month visits . RESULTS Three subjects had uncomplicated urinary tract infections during followup . No other adverse effects occurred . Statistically and clinical ly significant decreases greater than 50 % were seen in virtually all outcome measures at all visits up to 3 months . Most subjects showed signs of recurrent UUI by 6 months . All subjects reported remarkable subjective improvement in incontinence . No significant changes in maximal cystometric capacity , maximal detrusor pressure , peak flow or post-void residual volumes were seen . CONCLUSIONS Botulinum-A toxin can significantly decrease urge urinary incontinence and improve quality of life for 3 months after injection . Additional studies are needed to determine ideal doses , dosing intervals , safety and cost-effectiveness of this therapy OBJECTIVES To investigate the clinical and urodynamic effects of suburothelial injection of botulinum A toxin on patients with nonneurogenic detrusor overactivity . Intradetrusor injection of botulinum A toxin has been used to treat patients with detrusor overactivity .  Suburothelial injection of botulinum A toxin might effectively inhibit the occurrence of detrusor overactivity mediated by sensory nerves . METHODS Twenty patients with nonneurogenic detrusor overactivity refractory to anticholinergics were enrolled and treated with injection of 200 U botulinum A toxin into the suburothelial space . The clinical effects on the lower urinary tract symptoms and urodynamic parameters were assessed . RESULTS At 3 months after treatment , 9 patients had regained continence ( 45 % ) , 8 had improvement ( 40 % ) , and treatment had failed in 3 ( 15 % ) . At 6 months after treatment , 7 patients remained continent , but treatment had failed in 5 . Hematuria developed in 1 patient , urinary tract infection in 7 ( 35 % ) , and a large postvoid residual urine volume requiring catheterization in 6 ( 30 % ) . Hesitancy in initiation and difficult urination was also noted in 15 patients ( 75 % ) . The volume of the first sensation of bladder filling and bladder capacity increased about two times ; however , the voiding efficiency was reduced by 50 % at 2 weeks after treatment . The postvoid residual urine volume was increased by seven times the baseline value at 2 weeks and had decreased to three times greater at 3 and 6 months after treatment . CONCLUSIONS The results of this study have shown that suburothelial injection of 200 U botulinum A toxin impairs bladder sensation and voiding efficiency , but is effective in the treatment of nonneurogenic detrusor overactivity . Transient urinary retention and the development of urinary tract infection should be carefully monitored PURPOSE Several studies have shown that intradetrusor injections of botulinum neurotoxin type A ( BoNT/A ) may effectively treat intractable spinal neurogenic detrusor overactivity ( NDO ) , but fewer reports exist on the use of BoNT/A in patients with idiopathic detrusor overactivity ( IDO ) . The purpose of this study was to investigate whether comparable efficacy could be displayed in the response of patients with IDO to those with NDO . MATERIAL S AND METHODS In a prospect i ve , open label study , patients with urgency , and /or urgency incontinence due to urodynamically proven intractable detrusor overactivity received 300 units ( NDO ) or 200 units ( IDO ) of Botox injected into the bladder with a minimally invasive outpatient technique . Urodynamic maximum cystometric capacity and maximum detrusor pressure during filling , frequency of voids ( frequency ) , number of incontinence episodes ( leak ) and number of voids associated with urgency per 24 hours ( urgency ) from 4-day voiding diaries were compared between the 2 groups at baseline and for changes at 4 and 16 weeks after treatment . RESULTS A total of 44 patients with spinal NDO and 31 with IDO were treated . At 16 weeks , mean + /- st and ard error maximum cystometric capacity increased from 229.1 + /- 24.8 to 427.0 + /- 26.9 ml , p < 0.0001 in NDO and from 193.6 + /- 24.0 to 327.1 + /- 36.1 ml , p=0.0008 in IDO . Maximum detrusor pressure during filling decreased from 60.7 + /- 6.8 to 26.1 + /- 3.7 cm H2O , p < 0.0001 in NDO and from 62.1 + /- 10.8 to 45.1 + /- 8.1 cm H2O , p=0.027 in IDO . Frequency decreased from 12.3 + /- 0.7 to 6.6 + /- 0.6 voids per 24 hours , p < 0.0001 in NDO and from 13.6 + /- 1.1 to 8.3 + /- 0.7 , p=0.0002 in IDO . Leak decreased from 3.9 + /- 0.5 to 0.7 + /- 0.2 incontinence episodes per 24 hours , p < 0.0001 in NDO and from 3.2 + /- 0.8 to 0.6 + /- 0.3 , p=0.0017 in IDO , and urgency decreased from 7.5 + /- 0.6 to 1.44 + /- 0.3 episodes per 24 hours , p < 0.0001 in NDO and from 10.9 + /- 1.7 to 4.9 + /- 1.1 , p < 0.0001 in IDO . The 2 groups were comparable for baseline data , but percent improvement in urgency was greater in patients with NDO at 4 weeks ( 78.2 % vs 56.3 % , p=0.019 ) and 16 weeks ( 78.3 % vs 50.7 % , p=0.013 ) . Of patients with NDO 69 % required self-catheterization de novo posttreatment compared with 19.3 % of those with IDO . CONCLUSIONS Patients with intractable IDO respond to intradetrusor BoNT/A with equally significant improvements in urodynamic and lower urinary tract symptom parameters as those with spinal NDO , despite the lower dose of toxin used To assess , in a prospect i ve study , whether botulinum toxin A ( BTXA ) injected into the detrusor muscle is safe and well tolerated , produces significant changes in urodynamic variables , if the effect is durable , as measured by the Bristol Female Lower Urinary Tract Symptom Question naire ( BFLUTS ) , and to assess changes in quality of life , as measured by the Kings Health Question naire ( KHQ ) , when it is used to manage idiopathic detrusor overactivity ABSTRACT Objective : To evaluate the efficacy and safety of a single intra detrusor injection of BoNTA comparing two different doses ( 100 U or 200 U ) in patients with idiopathic overactive bladder . Material s and Methods : A r and omized prospect i ve study evaluated the efficacy of BoNTA in management of refractory idiopathic overactive bladder and included 80 patients . All patients were assessed initially by taking a history , a physical examination , overactive bladder symptom score , urine analysis , routine laboratory investigations , KUB and pelviabdominal . OABSS was adjusted on all patients postoperative at 1,3,6,9 months also Urodynamic was done for all patients preoperative and postoperative at 3 , 6 , 9 months . Results : The mean age was 30.22±8.37 and 31.35±7.61 in group I and II respectively . There was no statistically difference between both groups in all parameters all over the study except at 9 months after treatment . Hematuria was observed 6 and 9 patients in group I and II respectively . Dysuria was observed in 6 and 15 patients in group I and II respectively . UTI was detected in 3 and 7 patients in group I and II respectively . Conclusion : A single-injection procedure of 100 U or 200 U BoNTA is an effective and safe treatment for patients with IOAB who failed anticholinergic regimens . OABSS and QoL were improved for 6 months ; 100 U injections seemed to have comparable results with 200 U. There was a significant difference at month 9 towards 200 U with more incidences of adverse events Background Sacral neuromodulation is well established in the treatment of refractory , non-neurogenic lower urinary tract dysfunction , but its efficacy and safety in patients with lower urinary tract dysfunction of neurological origin is unclear . Only few case series have been reported for multiple sclerosis . We prospect ively evaluated the efficacy and safety of sacral neuromodulation in patients with multiple sclerosis . Methods Seventeen patients ( 13 women , 4 men ) treated with sacral neuromodulation for refractory neurogenic lower urinary tract dysfunction caused by multiple sclerosis were prospect ively enrolled ( 2007–2011 ) . Patients had to have stable disease and confirmed neurogenic lower urinary tract dysfunction .  Voiding variables , adverse events , and subjective satisfaction were assessed . Results Sixteen ( 94 % ) patients had a positive test phase with a > 70 % improvement . After implantation of the pulse generator ( InterStim II ) , the improvement in voiding variables persisted . At 3 years , the median voided volume had improved significantly from 125 ( range 0 to 350 ) to 265 ml ( range 200 to 350 ) ( p < 0.001 ) , the post void residual from 170 ( range 0 to 730 ) to 25 ml ( range 0 to 300 ) ( p = 0.01 ) , micturition frequency from 12 ( range 6 to 20 ) to 7 ( range 4 to 12 ) ( p = 0.003 ) , and number of incontinence episodes from 3 ( range 0 to 10 ) to 0 ( range 0 to 1 ) ( p = 0.006 ) . The median subjective degree of satisfaction was 80 % . Only two patients developed lack of benefit . No major complications occurred . Conclusions Chronic sacral neuromodulation promises to be an effective and safe treatment of refractory neurogenic lower urinary tract dysfunction in selected patients with multiple sclerosis BACKGROUND Neurogenic detrusor overactivity ( NDO ) frequently results in urinary incontinence ( UI ) which impairs quality of life ( QOL ) and puts the upper urinary tract at risk . OBJECTIVE To assess the effects of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) on UI , urodynamic variables , and QOL in incontinent patients with NDO . DESIGN , SETTING , AND PARTICIPANTS This multicentre , r and omised , double-blind , placebo-controlled study enrolled patients with multiple sclerosis ( MS ; n=154 ) or spinal cord injury ( SCI ; n=121 ) with UI due to NDO ( ≥14 UI episodes per week ) . INTERVENTION Patients received 30 intradetrusor injections of onabotulinumtoxinA 200 U ( n=92 ) , 300 U ( n=91 ) , or placebo ( n=92 ) , avoiding the trigone . MEASUREMENTS Primary end point was change from baseline in UI episodes per week ( week 6 ) . Secondary end points included urodynamics ( maximum cystometric capacity [ MCC ] , maximum detrusor pressure during first involuntary detrusor contraction [ P(detmaxIDC ) ] ) , and Incontinence Quality of Life ( I-QOL ) total score . Adverse events ( AEs ) were assessed . RESULTS AND LIMITATIONS At baseline , mean UI episodes per week ( 33.5 ) were similar across groups . At week 6 , onabotulinumtoxinA 200 U and 300 U significantly reduced UI episodes per week ( -21.8 and -19.4 , respectively ) compared with placebo ( -13.2 ; p<0.01 ) ; onabotulinumtoxinA benefit was observed by the first posttreatment study visit at week 2 . Improvements in MCC , P(detmaxIDC ) , and I-QOL at week 6 were significantly greater with both onabotulinumtoxinA doses than with placebo ( p<0.001 ) . Benefits were observed in both the MS and SCI population s. The median time to patient request for retreatment was the same for both onabotulinumtoxinA doses ( 42.1 wk ) and greater than placebo ( 13.1 wk ; p<0.001 ) . Most frequent AEs were localised urologic events ( urinary tract infections and urinary retention , which were dose related in patients not using clean intermittent catheterisation [ CIC ] at baseline ) . Significant increases in postvoid residual were observed in patients not using CIC prior to treatment , and 12 % , 30 % , and 42 % of patients in the placebo , 200-U , and 300-U groups , respectively , initiated CIC posttreatment . CONCLUSIONS OnabotulinumtoxinA significantly reduced UI and improved urodynamics and QOL in MS and SCI patients with NDO . Both doses were well tolerated with no clinical ly relevant differences in efficacy or duration of effect between the two doses ( http://www . clinical trials.gov ; NCT00461292 ) PURPOSE We assessed the efficacy , safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity . MATERIAL S AND METHODS In this 52-week , international , multicenter , double-blind , r and omized , placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence ( 14 or more episodes per week ) result ing from multiple sclerosis ( 227 ) and spinal cord injury ( 189 ) were treated with intradetrusor injections of onabotulinumtoxinA ( 200 or 300 U ) or placebo . The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6 . Maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points . Adverse events were monitored . RESULTS OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week , respectively , vs 9 episodes per week in 149 on placebo ( each dose p<0.001 ) . Also , maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group ( each dose p<0.001 ) . Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo ( 256 and 254 days , respectively , vs 92 ) . The most common adverse events were urinary tract infection and urinary retention . Of patients who did not catheterize at baseline 10 % on placebo , 35 % on 200 U and 42 % on 300 U initiated catheterization due to urinary retention . CONCLUSIONS OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo . Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion . No clinical ly relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose OBJECTIVE We investigated the effect of botulinum-a toxin injections into the detrusor and external sphincter muscle in patients with overactive bladder ( OAB ) symptoms . METHODS We included 44 patients - 41 women and three men with a mean age of 66.1 years - who were suffering from OAB symptoms that were refractory to anticholinergic treatment . We injected 200 - 300 U of BTX-A ( Botox ) into the detrusor muscle ; 22 patients also received external sphincter injections . For outcome analysis , we used a bladder diary , a urodynamic examination , and a question naire that consisted of 27 vali date d questions . RESULTS Changes in the bladder diary 4 weeks and 3 , 6 , and 9 months after BTX-A injection were as follows : Micturition frequency was reduced by 12 % , 16 % , 13 % and 9 % , respectively . Average pad use decreased from 4.2 pads per day to at most 2.4 pads per day after 6 months . Urodynamic changes were most distinct after 4 weeks : the volume when the first uninhibited detrusor contraction occurred increased from 149+/-18.2 mL to 263 + /- 24.2 mL , and maximum cystometric bladder capacity increased from 228 + /- 19.2 mL to 305 + /- 19.0 mL. Subjectively , 86 % of the patients would choose this procedure for their bladder condition again . Residua 4 weeks after additional injection into the sphincter muscle were distinctly smaller than in the " only detrusor " group . CONCLUSIONS BTX-A detrusor and sphincter injection is very effective in treating OAB symptoms . For patients who might be expected to have residual urine after injection only into the detrusor , additional injection of low doses of BTX-A into the external sphincter muscle could be one option to reduce that risk Purpose Many trials do not measure quality -adjusted life years ( QALYs ) . Therefore , decision analysts often map condition-specific outcomes to preference scores . We estimated the relationship between changes in preference scores and commonly reported condition-specific outcomes in patients with urinary incontinence ( UI ) due to neurogenic detrusor overactivity . Methods In 59 patients recruited to a neurogenic UI trial , clinical outcomes ( UI episodes ) , condition-specific quality of life ( Incontinence Quality of Life Instrument ( I-QOL ) ) , and SF-6D preference scores were measured at enrollment and 24 weeks . We used multiple linear regression to estimate the impact on SF-6D scores of 50 ; 50–99 and 100 % reductions in UI episodes and a 10-point improvement in I-QOL . Results By 24 weeks , mean ( 95 % CI ) daily UI episodes fell by 0.85 ( 0.04 , 1.3 ) and mean I-QOL scores improved by 18 ( 12 , 24 ) . SF-6D scores increased by 0.03 ( 0.003 , 0.058 ) , due to improvements in role limitations . A ≥ 50 % reduction in UI episodes was achieved by 49 % of patients and corresponded to a 0.09 ( 0.02 , 0.16 ) SF-6D increase . A ≥ 10-point increase in I-QOL was attained by 65 % of patients and was associated with a 0.05 ( −0.02 , 0.12 ) SF-6D increase . Conclusions These estimates provide preliminary data for decision analysts wishing to map neurogenic UI outcomes to preference scores PURPOSE Treatment options for patients with overactive bladder refractory to anticholinergics are limited . We assessed the dose response across a range of doses of onabotulinumtoxinA ( BOTOX ® ) in patients with idiopathic overactive bladder and urinary urgency incontinence whose symptoms were not adequately managed with anticholinergics .  MATERIAL S AND METHODS In a phase 2 , multicenter , r and omized , double-blind study , 313 patients with idiopathic overactive bladder and urinary urgency incontinence experiencing 8 or more urinary urgency incontinence episodes a week and 8 or more micturitions daily at baseline received 50 , 100 , 150 , 200 or 300 U intradetrusor onabotulinumtoxinA , or placebo . Symptoms were recorded using a 7-day bladder diary . The primary efficacy variable was weekly urinary urgency incontinence episodes and the primary end point was week 12 . RESULTS Demographics and baseline characteristics were balanced across the treatment groups . Durable efficacy was observed for all onabotulinumtoxinA dose groups of 100 U or greater for primary and secondary efficacy measures , including the proportion of incontinence-free patients . When the dose response curves were analyzed , doses greater than 150 U contributed minimal additional or clinical ly relevant improvement in symptoms . This finding was also reflected in health related quality of life assessment s. Dose dependent changes in post-void residual urine volume were observed and the use of clean intermittent catheterization was also dose dependent . The only adverse events significantly greater with onabotulinumtoxinA than with placebo were urinary tract infection and urinary retention . CONCLUSIONS OnabotulinumtoxinA at doses of 100 U or greater demonstrated durable efficacy in the management of idiopathic overactive bladder and urinary urgency incontinence . A dose of 100 U may be the dose that appropriately balances the symptom benefits with the post-void residual urine volume related safety profile AIMS To assess and compare the effect of botulinum A toxin ( BTX-A ) injections into the detrusor in idiopathic and neurogenic detrusor overactivity resistant to anticholinergic treatment . PATIENTS AND METHODS In a prospect i ve study , 11 patients with idiopathic and 11 with neurogenic detrusor overactivity resistant to anticholinergic treatment were injected with 300 U of BTX-A ( Botox ) into the detrusor . Clinical and urodynamic parameters were assessed before and after BTX-A injections . RESULTS In idiopathic as well as in neurogenic detrusor overactivity , median daytime frequency decreased significantly from 11 to 4 ( P = 0.004 ) and 12 to 5 ( P = 0.001 ) , median nocturia from 3 to 1 ( P = 0.004 ) and 3 to 1 ( P = 0.001 ) , and median number of used pads from 5 to 0 ( P = 0.001 ) and 5 to 0 ( P = 0.002 ) , respectively . There was a significant increase in median maximum cystometric capacity from 220 to 340 ml ( P = 0.001 ) and 190 to 410 ml ( to instead of ) ( P = 0.001 ) , median bladder compliance from 20 to 55 ml/cm H(2)O ( P = 0.001 ) and 23 to 60 ml/cm H(2)O ( P = 0.004 ) and median post void residual from 10 to 140 ml ( P = 0.002 ) and 30 to 240 ml ( P = 0.002 ) , respectively . Median maximum detrusor pressure decreased significantly from 45 to 29 cm H(2)O ( P = 0.002 ) and 40 to 24 cm H(2)O ( P = 0.002 ) , and median detrusor pressure at maximum flow rate from 30 to 14 ml/sec ( P = 0.001 ) and 38 to 21 ml/sec ( P = 0.016 ) , respectively . Due to post void residuals > 150 ml following BTX-A injections , de novo clean intermittent self-catheterization was necessary in nine patients ( four with idiopathic and five with neurogenic detrusor overactivity ) and in one patient ( with idiopathic detrusor overactivity ) a suprapubic catheter was placed . The effect of BTX-A injections lasted for a median time of 5 months in both idiopathic and neurogenic detrusor overactivity . There was no significant difference in idiopathic compared to neurogenic detrusor overactivity in regard to clinical and urodynamic parameters assessed before and after BTX-A injections . CONCLUSIONS BTX-A injections into the detrusor have a significant and comparable but temporally limited effect in idiopathic and neurogenic detrusor overactivity resistant to anticholinergic treatment PURPOSE In this prospect i ve , nonr and omized , ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment , such as anticholinergic drugs . MATERIAL S AND METHODS A total of 23 men and 77 women with a mean age of 63 years ( range 24 to 89 ) with nonneurogenic overactive bladder , including urgency-frequency syndrome , and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance . Micturition diary , full urodynamics , neurological status and urine probes were performed in all participants before treatment . Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings . Special attention was given to reflex volume , maximal bladder capacity , detrusor compliance , post-void residual urine , urgency and frequency/nocturia . Clinical , urodynamic and quality of life assessment s were performed at baseline , and 4 , 12 and 36 weeks after botulinum-A toxin treatment . RESULTS Overall after 4 and 12 weeks 88 % of our patients showed significant improvement in bladder function in regard to subjective symptoms , quality of life and urodynamic parameters ( p < 0.001 ) . Urgency disappeared in 82 % of the patients and incontinence resolved in 86 % within 1 to 2 weeks after botulinum-A toxin injections . Mean frequency decreased from 14 to 7 micturitions daily ( -50 % ) and nocturia decreased from 4 to 1.5 micturitions . Mean maximal bladder capacity increased 56 % from 246 to 381 ml , mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability ( mean reflex volume 169 ml ) resolved in 74 % of patients . Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml . There were no severe side effects except temporary urine retention in 4 cases . Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance . Mean efficacy duration + /- SD was at least approximately 6 + /- 2 months and then symptoms began to increase . CONCLUSIONS Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments AIMS We assessed the effects of onabotulinumtoxinA ( BOTOX ® ) on clinical and urodynamic variables in patients with idiopathic overactive bladder ( OAB ) and urinary urgency incontinence ( UUI ) with or without detrusor overactivity ( DO ) , inadequately managed with anticholinergics . METHODS Three hundred thirteen patients with OAB were r and omized to double-blind intradetrusor injection with placebo ( n = 44 ) or 1 of 5 onabotulinumtoxinA doses ( 50 - 300 U ; n = 269 ) . Primary efficacy variable was change from baseline in UUI episodes/week at week 12 . Urodynamic assessment s at baseline and weeks 12 and 36 included maximum cystometric capacity ( MCC ) and volume at first involuntary detrusor contraction ( IDC ) . RESULTS 76.0 % of patients had baseline DO . Changes from baseline in MCC and volume at first IDC with onabotulinumtoxinA ≥100 U were superior to placebo at week 12 , generally decreasing by week 36 . Significant dose-dependent increases in MCC were observed for all onabotulinumtoxinA doses at week 12 , and for 150 , 200 , and 300 U at week 36 . Data suggested a dose-response relationship . At week 12 on diary , 15.9 % of placebo and 29.8 - 57.1 % of onabotulinumtoxinA 50 - 300 U recipients , respectively , did not demonstrate UUI . OnabotulinumtoxinA doses > 150 U were more commonly associated with post-void residual urine volumes > 200 ml . CONCLUSIONS Improvements in urodynamic parameters and clinical outcomes generally trended together following onabotulinumtoxinA treatment . This therapy improved key urodynamic parameters in patients with idiopathic OAB and UUI , with no differences in outcomes between those with and those without baseline DO . Therefore , successful idiopathic OAB treatment with onabotulinumtoxinA does not appear to be related to pretreatment finding of DO
target: These and other outcomes for effectiveness of BTX-A at different dosages in two observation periods indicate that a dose greater than 50 U is significantly more effective for certain symptoms of OAB compared with placebo .
  However , there were no significant differences between some dosages .
  Compared with placebo , the outcomes of total adverse events for NDO and for IDO show that doses of 300 U and 200 U for NDO are associated with more complications .
  Conclusions In consideration that the treatments of BTX-A were with minimal , local , and manageable adverse effects , this meta- analysis demonstrates that BTX-A 200 U is recommended for management of NDO for short-term treatment for there was no significant difference from the larger dose of 300U .
background: Purpose To assess the effectiveness and safety of botulinum toxin A ( BTX-A ) at different dosages for overactive bladder ( OAB ) .