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OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis).

ABSTRACT: OBJECTIVE:To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS:This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or ?3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS:In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P < 0.001), and significantly greater improvement for all secondary end-points (P < 0.05). Urinary tract infection, dysuria, urinary retention and post-void residual urine volume increased represented adverse events occurring at a higher rate in the onabotulinumtoxinA group. The majority of these were mild or moderate in severity. CONCLUSIONS:Statistically significant and clinically relevant improvements in symptoms and patient-reported outcomes, and tolerability were seen in patients with overactive bladder and urinary incontinence who had been inadequately managed with overactive bladder medications after using onabotulinumtoxinA.

SUBMITTER: Yokoyama O

PROVIDER: S-EPMC7154639 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis).

Yokoyama Osamu O Honda Masashi M Yamanishi Tomonori T Sekiguchi Yuki Y Fujii Kenji K Nakayama Takashi T Mogi Takao T

International journal of urology : official journal of the Japanese Urological Association 20200120 3

<h4>Objective</h4>To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence.<h4>Methods</h4>This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β<sub>3</sub> -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinum ...[more]

PMID: 31957922

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Project description: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).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.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.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. ClinicalTrials.gov: NCT00910845, NCT00910520.

Project description:PurposeWe systematically reviewed preclinical and clinical studies on bladder chemodenervation with onabotulinumtoxin A to highlight current limitations and future drug delivery approaches.Materials and methodsWe identified peer reviewed basic and clinical research studies of onabotulinumtoxin A in the treatment of neurogenic bladder and refractory idiopathic overactive bladder published between March 2000 and March 2016. Paired investigators independently screened 125 English language articles to identify controlled studies on onabotulinumtoxin A administration in the MEDLINE® database and abstracts presented at annual American Urological Association meetings. The review yielded an evidence base of more than 50 articles relevant to the approach of injection-free onabotulinumtoxin A chemodenervation.ResultsThe efficacy and safety of intradetrusor injection of onabotulinumtoxin A for the treatment of overactive bladder are sensitive to injection volume and depth, and this issue has motivated researchers to study injection-free modes of drug delivery into the bladder. Urothelial denudation with protamine sulfate or dimethyl sulfoxide, liposome encapsulated onabotulinumtoxin A and other physical approaches are being studied to increase toxin permeability and avoid intradetrusor injections. Liposome encapsulated onabotulinumtoxin A enhances toxin activity while reducing its toxin degradation. The safety and efficacy of liposome encapsulated onabotulinumtoxin A were tested in a multicenter, placebo controlled study. Although this treatment successfully reduced urinary frequency and urgency, it did not significantly reduce urgency urinary incontinence episodes.ConclusionsIntradetrusor injection of onabotulinumtoxin A is a safe and effective treatment as reported in several large multicenter, randomized controlled trials. Injection of the toxin into the bladder wall impairs afferent and efferent nerves, but injection-free drug delivery approaches only impair the bladder afferent nerves. Further studies are needed to develop better drug delivery platforms that overcome the drawbacks of intradetrusor injection, increase patient acceptance and reduce treatment costs.

Project description:OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB).To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB.Network meta-analysis.A search of 9 electronic databases, review documents, guidelines and websites.Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR).No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis.In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB.

Dataset Information

OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis).

Publications

OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis).

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