Karny Jacoby

OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial

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. Materials 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 randomized 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, clinically relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated.

DOUBLE BALLOON POSITIVE PRESSURE URETHROGRAPHY IS A MORE SENSITIVE TEST THAN VOIDING CYSTOURETHROGRAPHY FOR DIAGNOSING URETHRAL DIVERTICULUM IN WOMEN

PURPOSE We determined the relative sensitivity of double balloon positive pressure urethrography and voiding cystourethrography for diagnosing urethral diverticula in women, and for evaluating which presenting symptoms should be considered clinically suspicious for even smaller diverticula. MATERIALS AND METHODS The series comprised 32 women, including those with new onset urinary tract infections not related to intercourse, menopause or catheters, those with urethral symptoms, such as point urethral tenderness or a mass, urethral pain, dysuria, dyspareunia or post-void dribbling, and those with new onset urgency and frequency. All patients underwent a history and physical examination by the same physician. Each patient underwent double balloon urethrography and voiding cystourethrography on the same day at a single radiology department. RESULTS Of the 32 women 30 (94%) were diagnosed with at least 1 diverticulum by double balloon urethrography. In 22 of these cases voiding cystourethrography failed to show the diverticulum. Only 11 of these patients (37%) had a palpable mass on clinical examination. The most common presenting symptoms in patients diagnosed with a diverticulum were recurrent urinary tract infection (52%), dysuria (52%), urgency (41%), frequency (38%), stress incontinence (38%) and urge incontinence (34%). Only 3 patients (9%) presented with 1 symptom. Diverticulectomy was performed in 16 patients. Double balloon urethrography had greater sensitivity (100%) than voiding cystourethrography (44%) relative to a confirmed surgical diagnosis (z test p = 0.002). Of 9 diverticula missed by voiding cystourethrography in the surgery group the maximum diameter was less than 15 mm. in 5. Average followup in the surgery cases is 34 months (median 35, range 17 to 50). None of these patients has had new symptoms suggestive of recurrent diverticulum, failure, new urethritis or new stress urinary incontinence. Conservative therapy consisted of long-term antibiotics in 6 patients and symptomatic treatment with short-term antibiotics in the remaining 8. Conservative therapy offered symptomatic relief in most cases but did not prevent recurrent symptoms. CONCLUSIONS A diverticulum should be suspected in patients with new onset urinary tract infection, urgency and frequency as well as dyspareunia, post-void dribbling and dysuria. Double balloon urethrography is a more sensitive diagnostic test than voiding cystourethrography for diagnosing urethral diverticula. Patients with mild symptoms may be treated with conservative therapy, although we believe that satisfactory long-term treatment of diverticula is best achieved by surgical excision.

Three-month primary efficacy data for the SUCCESS Trial; a phase III, multi-center, prospective, randomized, controlled study treating female stress urinary incontinence with the vesair intravesical balloon

The SUCCESS trial is a phase III study of the Vesair® balloon in the United States for female stress urinary incontinence (SUI). The purpose of this manuscript is to present the 3 month primary efficacy and tolerability outcome data.

Twelve-Month Efficacy and Safety Data for the "Stress Incontinence Control, Efficacy and Safety Study": A Phase III, Multicenter, Prospective, Randomized, Controlled Study Treating Female Stress Urinary Incontinence Using the Vesair Intravesical Balloon.

Objectives The “Stress Incontinence Control, Efficacy and Safety Study” (SUCCESS) is a phase III study of the Vesair Balloon in women with stress urinary incontinence who had failed conservative therapy, and either failed surgery, were not candidates for surgery, or chose not to have surgery. The safety and efficacy of the balloon at 12 months is reported for those participants in the treatment arm who elected to continue with the SUCCESS trial beyond the primary end point at 3 months. Methods The SUCCESS trial is a multicenter, prospective, single-blinded, randomized, sham-controlled study. Participants were randomized on a 2.33:1 basis to either Vesair Balloon placement or placebo. The primary efficacy end point was a composite of both a greater than 50% reduction from baseline on 1-hour provocative pad weight test and an at least 10-point improvement in symptoms on the Incontinence Quality of Life questionnaire assessed at the 3-month study visit. Patients in the treatment arm who opted to continue in the trial were followed up prospectively up to 12 months. Results A total of 221 participants were randomized, including 157 in the treatment arm and 64 in the control arm. Sixty-seven participants in the treatment arm (42.7% of participants enrolled) were evaluated at 12 months, with 56.3% achieving the composite end point and 78.7% having greater than 50% reduction in pad weight from baseline in a per-protocol analysis. In an intent-to-treat analysis treating all participants who did not continue with the balloon as failures, 24% of the participants achieved the composite end point and 33.6% had a greater than 50% reduction in pad weight from baseline. Treatment-related adverse events in this group included dysuria (40.1%), gross hematuria (36.9%), and urinary tract infection (26.1%). Conclusions In this phase III trial, symptom relief was maintained for those participants who continued therapy for 12 months. The balloon was found to be safe with no device- or procedure-related serious adverse events reported. Additional studies are warranted to determine which patient populations are more tolerant of the balloon and to assess the efficacy and safety of its longer-term use. Additional screening methods, including screening patients for balloon tolerability, are warranted to reduce participant withdrawals.