OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3 Randomized Placebo-Controlled Trial
Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, Yan X, Haag-Molkenteller C; EMBARK Study Group. J Urol. 2012 Dec 13. pii: S0022-5347(12)05849-1. doi: 10.1016/j.juro.2012.12.022. [Epub ahead of print]

Source

New York University Urology Associates, New York, New York. Electronic address: Victor.Nitti@nyumc.org.

Abstract

PURPOSE:

Overactive bladder (OAB) affects 12%-17% of the general population; nearly one-third suffer from urinary incontinence (UI), which may severely impact health-related quality of life (HRQOL). Oral anticholinergics are the mainstay of pharmacologic treatment, but are limited by inadequate efficacy or side effects leading to high discontinuation rates. We report results of the first large (N=557) phase 3 placebo-controlled trial of onabotulinumtoxinA in OAB patients with UI who were inadequately managed with anticholinergics.

METHODS:

Eligible OAB patients with ≥3 urgency UI episodes in 3 days and ≥8 micturitions/day were randomized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100U or placebo. Co-primary endpoints were change from baseline in UI episodes/day and proportion of patients with a positive response on the treatment benefit scale (TBS) at week 12 post-treatment. Secondary endpoints included other OAB symptoms and HRQOL. Adverse events (AE) were assessed.

RESULTS:

OnabotulinumtoxinA significantly reduced the daily frequency of UI episodes versus 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-treated patients than placebo reported a positive response on the TBS (60.8% vs 29.2%; p <0.001). All other OAB symptoms improved versus placebo (p ≤0.05). OnabotulinumtoxinA improved patients' HRQOL across multiple measures (p <0.001). Uncomplicated urinary tract infection was the most common AE. A low rate of urinary retention (5.4%) was observed.

CONCLUSIONS:

OnabotulinumtoxinA 100U demonstrated significant and clinically relevant improvements in all OAB symptoms and HRQOL in patients who were inadequately managed with anticholinergics and was well-tolerated.