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.

Pentosan polysulfate sodium for treatment of interstitial cystitis/bladder pain syndrome: insights from a randomized, double-blind, placebo controlled study.

PURPOSE: We compared the efficacy and safety of the currently recommended dose of pentosan polysulfate sodium with a third of the daily dose and with placebo. MATERIALS AND METHODS: In this multicenter, double-blind, randomized, placebo controlled study 368 adults with interstitial cystitis/bladder pain syndrome, defined as an ICSI total score of 8 or greater and a score of greater than 0 on the 4 ICSI component items, received pentosan polysulfate sodium 100 mg once daily or 3 times daily, or matching placebo for 24 weeks. Study eligibility was not based on cystoscopy findings. ICSI was administered at baseline, and at weeks 4, 8, 12, 18 and 24. Unblinded interim analysis performed at 6 years with 54% of the target number of 645 patients enrolled resulted in early study termination. RESULTS: There was no statistically significant difference between the pentosan polysulfate sodium group and the placebo group or between the 2 pentosan polysulfate sodium groups for the primary end point, defined as responder achieving a 30% or greater reduction from the baseline ICSI total score at study end. This primary end point was achieved by 48 of 118 patients (40.7%) in the placebo group, and by 51 of 128 (39.8%) and 52 of 122 (42.6%) in the pentosan polysulfate sodium 100 mg once daily and 3 times daily groups, respectively. Pentosan polysulfate sodium was well tolerated with a similar percent of patients (range 10.2% to 13.3%) across the groups discontinuing due to an adverse event. CONCLUSIONS: Results of this study in a broad population of patients with symptoms consistent with interstitial cystitis revealed no treatment effect vs placebo for pentosan polysulfate sodium at the currently established dose or at a third of the daily dose.