Botulinum toxin injections for Japanese patients with urinary incontinence caused by neurogenic detrusor overactivity: Clinical evaluation of onabotulinumtoxinA in a randomized, placebo-controlled, double-blind trial with an open-label extension.
Ontology highlight
ABSTRACT: Objective
To assess the efficacy and safety of botulinum toxin treatment (onabotulinumtoxinA 200 units) for Japanese patients with neurogenic detrusor overactivity caused by spinal cord injury or multiple sclerosis.Methods
Patients with urinary incontinence refractory to pharmacological treatment were enrolled and randomized in a phase III trial. A single dose of onabotulinumtoxinA (n = 11) or placebo (n = 10) was given in the double-blind phase, and repeat injections of onabotulinumtoxinA were given in the subsequent open-label phase. Outcomes included urinary incontinence episodes, urodynamics, patient-reported outcomes and adverse events.Results
The onabotulinumtoxinA group showed a numerically greater reduction in the number of urinary incontinence episodes per day than the placebo group, with the difference between the groups at week 6 of -3.02 (95% confidence interval -5.85 to -0.19). The onabotulinumtoxinA group also showed greater improvements in urodynamic assessments. Adverse events related to onabotulinumtoxinA injections were hematuria, urinary retention, urinary bladder hemorrhage, autonomic dysreflexia and epididymitis. Most events were deemed mild or moderate.Conclusions
Intradetrusor injections of onabotulinumtoxinA are efficacious and tolerable for Japanese patients with neurogenic detrusor overactivity-related symptoms that are difficult to manage with anticholinergics and/or β3 -adrenergic receptor agonists.
SUBMITTER: Honda M
PROVIDER: S-EPMC8453759 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:AimsThis study evaluated whether one (or more) of three doses of onabotulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children.MethodsThis was a 48-week prospective, multicenter, randomized, double-blind study in children (aged 5-17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed.ResultsThere was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (-1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%-80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6-63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, -12.9; 100 U, -20.1; 200 U, -27.3 cmH2 O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent.ConclusionsOnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.
| S-EPMC7839517 | biostudies-literature
Project description:IntroductionTo evaluate the efficacy and safety of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity (NDO) in subpopulations of etiology (multiple sclerosis [MS] or spinal cord injury [SCI]) and concomitant anticholinergics (use/non-use).MethodsData 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.ResultsSignificant 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 subpopulation. 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.ConclusionRegardless 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.
| S-EPMC3824824 | biostudies-literature
Project description:ObjectivesTo evaluate the cost effectiveness of onabotulinumtoxinA (BOTOX(®), 200 units [200 U]) for the management of urinary incontinence (UI) in adults with neurogenic detrusor overactivity (NDO) due to subcervical spinal cord injury or multiple sclerosis that is not adequately managed with anticholinergic drugs (ACHDs).PerspectiveUK National Health Service (NHS) perspective.MethodsA Markov state-transition model was developed, which compared onabotulinumtoxinA + best supportive care (BSC) with BSC alone (comprising behavioural therapy and pads, alone or in combination with clean intermittent catheterization and possibly with ACHDs). Non-responders were eligible for invasive procedures. Health states were defined according to the reduction in UI episodes. Efficacy data and estimates of resource utilization were pooled from 468 patients on onabotulinumtoxinA in two phase III clinical trials. Drug costs (2013) and administration costs (NHS Reference Costs 2011-2012) were obtained from published sources. The time horizon of the model was 5 years, and costs and benefits were discounted at 3.5%. Scenario, one-way and probabilistic sensitivity analyses (PSAs) were conducted to explore uncertainties around the assumptions.ResultsIn the base case, treatment with onabotulinumtoxinA + BSC over 5 years was associated with an increase in costs of £1,689 and an increase in quality-adjusted life-years (QALYs) of 0.4, compared with BSC alone, resulting in an incremental cost-effectiveness ratio of £3,850 per QALY gained. Sensitivity analyses showed that utility values had the greatest influence on model results. PSA suggests that onabotulinumtoxinA + BSC had a 100 % probability of being cost effective at a willingness to pay of <£20,000.ConclusionFor adult patients with NDO who are not adequately managed with ACHDs, onabotulinumtoxinA + BSC appears to be a cost-effective use of resources in the UK NHS.
| S-EPMC4381108 | biostudies-literature
Project description:ObjectiveTo 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).MethodsIn this multicenter, double-blind, randomized, placebo-controlled, phase III, 52-week study (ClinicalTrials.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) Questionnaire total score, and the 3 domain scores (avoidance and limiting behavior, psychosocial, and social embarrassment), the modified Overactive Bladder Patient Satisfaction with Treatment Questionnaire (OAB-PSTQ), and Patient Global Assessment. Assessments were made at baseline, posttreatment week 6 (primary time point), week 12, and at 12-week intervals.ResultsPatients (mean age of 46 years with 30.5 weekly UI episodes at baseline) were randomized 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 Questionnaire 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).ConclusionsPatients 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 evidenceThis 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.
| S-EPMC3908462 | biostudies-literature
Project description:Many of the patients undergoing intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity (NDO) present with chronic bacteriuria. In these patients, antibiotic prophylaxis has been widely recommended since bacteriuria might impair treatment efficacy and cause urinary tract infections (UTI) but the evidence is limited. The aim of this study was to evaluate if an antibiotic prophylaxis is needed in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections. Between 06/2012 and 12/2014, a consecutive series of 154 patients undergoing a total of 273 treatment cycles were prospectively evaluated. Before treatment urine samples were collected, patients with no clinical signs for UTI underwent onabotulinumtoxinA injections, no antibiotic prophylaxis was given. Asymptomatic bacteriuria was found in 73% (200/273 treatments). Following treatment, UTI occurred in 5% (9/200) and 7% (5/73) of patients with and without bacteriuria, respectively. Intradetrusor onabotulinumtoxinA injections were clinically and urodynamically successful in 70% (192/273). There was no association between bacteriuria and treatment-related adverse events (odds ratio 0.64, 95% CI 0.23-1.81, p = 0.4) nor between bacteriuria and therapy failure (odds ratio 0.78, 95% CI 0.43-1.43, p = 0.4). Thus, we conclude that antibiotic prophylaxis needs to be critically reconsidered in patients undergoing intradetrusor onabotulinumtoxinA injections, especially taking into account the alarming antibiotic resistance worldwide.
| S-EPMC5019002 | biostudies-literature
Project description:BackgroundThe control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood.Methods/designThis is a prospective structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Neuroimaging data will include structural magnetic resonance imaging (T1-weighted imaging and diffusion tensor imaging) as well as functional, i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner. The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system.All subjects will undergo two consecutive and identical magnetic resonance imaging measurements. Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Parameters of the clinical assessment including bladder diary, urinalysis, medical history, neuro-urological examination, urodynamic investigation as well as standardised questionnaires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis.DiscussionThis study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls. Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control.Trial registrationClinicalTrials.gov NCT01768910.
| S-EPMC4144688 | biostudies-literature
Project description:Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)-modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, ?SMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.
| S-EPMC5742717 | biostudies-literature
Project description:Neurogenic detrusor overactivity (NDO) affects the quality of life (QoL) of millions of individuals worldwide. The purpose of this study was to assess the efficacy and safety of onabotulinumtoxinA in patients with NDO using a network meta-analytic approach, which can also quantify and compare the efficacy of onabotulinumtoxinA across different dosages.PubMed, EMBASE, and the Controlled Trials Register were searched to identify randomized controlled trials comparing onabotulinumtoxinA to a control for NDO in adult patients. The primary outcome was the mean number of urinary incontinence (UI) episodes per week. Urodynamic parameters included the maximum cystometric capacity (MCC) and the maximum detrusor pressure (MDP). The safety of onabotulinumtoxinA was determined by the incidence of various frequent adverse events (AEs). Two authors extracted data independently, and the statistical analyses were performed using RevMan 5.1.0 software.A total of 1,915 patients from six randomized controlled trials were included in this meta-analysis. The onabotulinumtoxinA-treated groups had a significantly decreased mean number of urinary incontinence episodes per week (at week 6) (onabotulinumtoxinA200U: MD: -10.72, 95% CI: -13.4 to -8.04, P<0.00001; 300 U: MD: -11.42, 95% CI: -13.91 to -8.93, P<0.00001), MDP (200 U: MD: -33.46, 95% CI: -39.74 to -27.18, P<0.00001; 300 U: MD: -31.72, 95% CI: -37.69 to -25.75, P<0.00001), and greater increased MCC (200 U: MD: 141.30, 95% CI: 121.28 to 161.32, P<0.00001; 300 U: MD: 151.39, 95% CI: 130.43 to 172.34, P<0.00001) compared to the placebo-treated groups. However, there were no significant differences between the onabotulinumtoxinA-treated groups for the number of weekly UI episodes at 6 weeks (MD: 0.08, 95% CI: -2.57 to 2.73, P = 0.95). Similarly, we also observed that there were no significant differences in MCC (MD: -9.97, 95% CI: -33.15 to 13.20, P = 0.40) and MDP (MD: -1.86, 95% CI: -8.09 to 4.37, P = 0.56). Considering the AEs, the onabotulinumtoxinA-treated groups were often associated with more complications, including urinary tract infections (UTIs) (RR: 1.47, 95% CI: 1.29 to 1.67, P<0.00001), urinary retention (RR: 5.58, 95% CI: 3.53 to 8.83, P<0.00001), hematuria (RR: 1.70, 95% CI: 1.01 to 2.85, P = 0.05), and muscle weakness (RR: 2.59, 95% CI: 1.36 to 4.91, P = 0.004).OnabotulinumtoxinA can significantly reduce the frequency of urge urinary incontinence and improve urodynamic parameters (MCC and MDP) in patients with NDO at 6 weeks after treatment. This meta-analysis indicates that onabotulinumtoxinA is effective and safe for treating patients with NDO compared to placebo. Additionally, we did not observe any statistical or clinical differences in efficacy between 300 and 200 U dosages.
| S-EPMC4963110 | biostudies-literature
Project description:The aim of this investigation was to characterize and compare the pharmacokinetics (PK) of the antimuscarinic drug solifenacin in pediatric patients with overactive bladder (OAB) or neurogenic detrusor overactivity (NDO) utilizing data from three phase III trials. LION was a placebo-controlled, 12-week trial in children (5-<12 years) and adolescents (12-<18 years) with OAB. MONKEY and MARMOSET were open-label, 52-week trials in children and adolescents or younger children (6 months-<5 years), respectively, with NDO. During the trials, solifenacin doses could be titrated to weight-adjusted pediatric equivalent doses (PEDs) of 2.5, 5, 7.5, or 10 mg day-1 . Nonlinear mixed effects modeling was used to develop population PK models to characterize the PK in patients with either OAB or NDO. Overall, 194 children and adolescents received solifenacin. At the time of PK sampling, the majority (119/164 [72.6%] patients) were receiving PED10 once daily. All population models included first-order oral absorption, a lag time, and interindividual variability. PK analysis showed that apparent clearance was similar in both patient populations. Mean apparent oral plasma clearance (CL/F), apparent volume of distribution during the terminal phase (Vz /F), and terminal half-life (t1/2 ) were higher in adolescents than in children, but median time to maximum plasma concentration (tmax ) was similar. Dose-normalized exposure results were similar for both younger and older patients with OAB or NDO. In conclusion, population PK modeling was used to successfully characterize solifenacin PK in pediatric patients with OAB or NDO. Similar solifenacin PK characteristics were observed in both populations.
| S-EPMC7685239 | biostudies-literature
Project description:BackgroundAnticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed.MethodsWe performed a double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events.ResultsOf 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P=0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P=0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P=0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P=0.01) and urinary tract infections (13% vs. 33%, P<0.001).ConclusionsOral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of daily episodes of urgency urinary incontinence. The group receiving onabotulinumtoxinA was less likely to have dry mouth and more likely to have complete resolution of urgency urinary incontinence but had higher rates of transient urinary retention and urinary tract infections. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.).
| S-EPMC3543828 | biostudies-literature