Efficacy and Safety of AbobotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Incontinence Performing Regular Clean Intermittent Catheterization: Pooled Results from Two Phase 3 Randomized Studies (CONTENT1 and CONTENT2).

BACKGROUND: For patients with neurogenic detrusor overactivity incontinence (NDOI), treatment with oral medications is often unsatisfactory. OBJECTIVE: To assess the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) for NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two randomized, double-blind phase 3 studies (CONTENT1, NCT02660138; CONTENT2, NCT02660359) enrolled patients with NDOI who were regularly performing clean intermittent catheterization (CIC) and were inadequately managed with oral therapy. Pooled results from the first placebo-controlled treatment cycle are reported. INTERVENTION: Patients received injections of aboBoNT-A 600 U (n = 162) or 800 U (n = 161) or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the mean change from baseline in NDOI episodes per week at week 6. Secondary endpoints reported are the proportion of patients with no NDOI episodes, the volume per void, urodynamic parameters, and quality of life (QoL). Safety was also assessed. Statistical analyses were conducted for the pooled study populations (each aboBoNT-A dose vs placebo). RESULTS AND LIMITATIONS: At week 6, NDOI episodes per week were significantly reduced in each aboBoNT-A group versus placebo (both p < 0.001) and the volume per void had significantly increased. Approximately one-third of patients in each aboBoNT-A dose group reported no NDOI episodes versus 3% of patients in the placebo group. Reductions in urinary incontinence (UI) were reflected in significantly greater improvements in UI-related QoL in the aboBoNT-A groups versus placebo. Urodynamic parameters (bladder capacity and detrusor pressure) were significantly improved with each aboBoNT-A dose versus placebo. Each aboBoNT-A dose was well tolerated. Symptomatic urinary tract infection was the most frequent treatment-emergent adverse event, with incidence comparable across the aboBoNT-A and placebo groups. The studies were terminated prematurely owing to slow recruitment and were not designed for statistical comparison between the two aboBoNT-A doses. CONCLUSIONS: Intradetrusor aboBoNT-A is an effective treatment and alternative option for patients with NDOI who have an inadequate response to oral anticholinergics and are already performing CIC. PATIENT SUMMARY: In patients with bladder muscle overactivity caused by neurological conditions (multiple sclerosis or spinal cord injury) and resulting in urinary incontinence, abobotulinumtoxinA injections improved their symptoms and bladder function, with no unexpected effects.

Management of LUTS in patients with dementia and associated disorders .

AIMS: To systematically review the management of lower urinary tract symptoms (LUTS) in patients with dementia and associated disorders. METHODS: This systematic review was performed according to the PRISMA statement. Studies were identified by electronic search of Embase and Medline databases (last search August 2015) and by screening of reference lists and reviews. RESULTS: Of 1,426 abstracts that were screened, 102 full-text articles were identified and assessed for eligibility. Seventy-six articles were then included in the quantitative synthesis. Urinary incontinence (UI) prevalence rates in dementia patients have varied considerably, ranging from 11 to 93%. In Alzheimer's disease patients, UI usually correlates with disease progression (late-stage dementia). In contrast, LUTS usually precede severe mental failure in Lewy body disease and in vascular dementia. Behavioral therapy, including toilet training and prompted voiding, may be especially useful in patients with unawareness UI. High-quality data to guide the choice of treatment strategies in this population are lacking. Current evidence suggests that antimuscarinics, especially oxybutynin, can be associated with cognitive worsening, due to the blockade of M1 receptors. Thus, the use of antimuscarinics that do not easily cross the blood-brain barrier or are more M2/M3 selective should be considered. No data are available for beta-3 agonists so far. CONCLUSION: Different types of dementia cause different LUTS at varying time points during the disease process and need singular therapeutic approaches. Treatment of LUTS should be tailored to individual patient needs and disease status, considering factors like mobility, cognitive function, and general medical condition. Neurourol. Urodynam. 36:245-252, 2017. © 2015 Wiley Periodicals, Inc.