Early and Consistent Improvements in Urinary Symptoms and Quality of Life With OnabotulinumtoxinA in Patients With Overactive Bladder and Urinary Incontinence: Results From a Randomized, Placebo-controlled, Phase IV Clinical Trial

Abstract

Objectives: This randomized, multicenter, placebo-controlled, phase IV study assessed the efficacy and tolerability of onabotulinumtoxinA in patients with overactive bladder.

Methods: Patients were randomized 1:1 to onabotulinumtoxinA 100 U or placebo. Assessments over 12 weeks included: change from baseline in urinary incontinence (UI) episodes/day; proportions of patients who achieved 100% and 50% or greater reductions in UI episodes/day; proportion of patients using no incontinence pads in the previous 24 hours; and changes from baseline in micturition frequency, nocturia, urgency UI, Incontinence-Quality of Life, King's Health Questionnaire, International Consultation on Incontinence Questionnaire-UI Short Form scores and time to request retreatment.

Results: Significant reductions in UI episodes/day were seen with onabotulinumtoxinA versus placebo within week 1 posttreatment (-2.9 vs -2.0, P = 0.005) through week 12 (coprimary endpoint: -3.5 vs -1.6, P < 0.001). Significantly more onabotulinumtoxinA-treated patients achieved 100% (coprimary endpoint) and 50% or greater reductions in UI episodes/day. Decreases in other urinary symptoms were also seen within 1 week with onabotulinumtoxinA that continued through at least week 12. More onabotulinumtoxinA-treated versus placebo-treated patients required no incontinence pads at weeks 1 to 12, and greater improvements in quality of life measurements were seen. Time to request retreatment was significantly longer with onabotulinumtoxinA versus placebo (30.0 weeks vs 13.1 weeks; P < 0.001). No unexpected safety signals were observed. Urinary tract infection was the most commonly observed adverse event.

Conclusions: Urinary symptom and quality of life improvements were observed with onabotulinumtoxinA within 1 week of treatment and were sustained for at least 12 weeks.

Trial registration: ClinicalTrials.gov NCT01945489 NCT00910845.

Conflict of interest statement

Conflicts of Interest and Source of Funding: This study and its analysis were sponsored by Allergan plc, Dublin, Ireland. Medical writing and editorial assistance was provided by Jennifer L. Giel, PhD, CMPP, and Karen Pemberton, PhD, CMPP, on behalf of Evidence Scientific Solutions, Inc., Philadelphia, PA, and was funded by Allergan plc, Dublin, Ireland.

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1

Improvement in UI episodes after treatment. A, LS mean change from BL. B, Proportion of patients with 100% reduction. C, Proportion of patients with ≥50% reduction. *P = 0.005; †P = 0.003; ‡P < 0.001 vs placebo. P values (A) were based on analysis of covariance with treatment as a factor and baseline value as a covariate. P values from (B) were from a Cochran-Mantel-Haenszel test adjusting for the randomization stratification factor (urinary incontinence at baseline: ≤9 episodes, >9 episodes). Missing values were imputed using last observation carried forward at the follow-up visits. LS, least squares; onabotA, onabotulinumtoxinA; BL, baseline.

FIGURE 2

A, Proportion of patients using no incontinence pads in the previous 24 hours in the 12 weeks after treatment. B, Mean change from BL in the single-item domain for incontinence impact of the KHQ over 12 weeks after treatment. *P < 0.001 vs placebo. Note: Statistical comparisons not performed for pad use. N values denote the number of patients with data available at the evaluated time point.

FIGURE 3

Quality-of-life improvements over 12 weeks after treatment. Mean change from BL in (A) KHQ role limitations, (B) KHQ social limitations, (C) I-QOL total summary score, and (D) ICIQ-UI after treatment up to week 12. *P < 0.001; †P = 0.006 vs placebo (KHQ, −5 points; I-QOL, 10 points) onabotA, onabotulinumtoxinA.