Comparison of 100 U With 200 U of Intradetrusor OnabotulinumToxinA for Nonneurogenic Urgency Incontinence

Abstract

Objectives: The objective of this study was to compare efficacy and adverse events between 100 U and 200 U of onabotulinumtoxinA for 6 months in women with nonneurogenic urgency incontinence.

Methods: This is a secondary analysis of 2 multicenter randomized controlled trials assessing efficacy of onabotulinumtoxinA in women with nonneurogenic urgency incontinence; one compared 100 U to anticholinergics and the other 200 U to sacral neuromodulation. Of 307 women who received onabotulinumtoxinA injections, 118 received 100 U, and 189 received 200 U. The primary outcome was mean adjusted change in daily urgency incontinence episodes from baseline over 6 months, measured on monthly bladder diaries. Secondary outcomes included perceived improvement, quality of life, and adverse events. The primary outcome was assessed via a multivariate linear mixed model.

Results: Women receiving 200 U had a lower mean reduction in urgency incontinence episodes by 6 months compared with 100 U (-3.65 vs -4.28 episodes per day; mean difference, 0.63 episodes per day [95% confidence interval (CI), 0.05-1.20]). Women receiving 200 U had lower perceptions of improvement (adjusted odds ratio, 0.32 [95% CI, 0.14-0.75]) and smaller improvement in severity score (adjusted mean difference, 12.0 [95% CI, 5.63-18.37]). Upon subanalysis of only women who were treated with prior anticholinergic medications, these differences between onabotulinumtoxinA doses were no longer statistically significant. There was no statistically significant difference in adverse events in women receiving 200 U (catheterization, 32% vs 23%; adjusted odds ratio, 1.4 [95% CI, 0.8-2.4]; urinary tract infection, 37% vs 27%; adjusted odds ratio, 1.5 [95% CI, 0.9-2.6]).

Conclusions: A higher dose of onabotulinumtoxinA may not directly result in improved outcomes, but rather baseline disease severity may be a more important prediction of outcomes.

Trial registration: ClinicalTrials.gov NCT01166438 NCT01502956.

Conflict of interest statement

E.S.L. received royalties from UpToDate. The remaining authors have declared they have no conflicts of interest.

Copyright © 2021 American Urogynecologic Society. All rights reserved.

Figures

FIGURE 1.

Change from baseline in UUIEs per day for each BoNT-A dose by month and baseline urgency incontinence episodes per day. Values are estimated marginal means, and associated 95% CIs are calculated from the multivariate linear mixed model with fixed effects of time, BoNT-A dose, baseline UUIE, age, baseline IIQ-SF, ethnicity, baseline UUIE by BoNT-A dose interaction, time by BoNT-A dose interaction, and participant ID as random effect; models based on n = 118 for 100 U and n = 189 for 200 U. BoNT-A, onabotulinumtoxinA; IIQ-SF, Incontinence Impact Questionnaire—Short Form; UUIEs, urgency urinary incontinence episode.

FIGURE 2.

Kaplan-Meier curve and risk table for time to recurrence over 6 months by BoNT-A dose. aProportionality assumption was not met for BoNT-A dose because of crossing hazards; thus, hazard ratios were calculated for 1 to 3 months and 4 to 6 months. Model adjusted for age, baseline UUIE per day, baseline UDI-SF, ethnicity, maximum cystometric capacity; models based on n = 118 for 100 U and n = 189 for 200 U. BoNT-A, onabotulinumtoxinA; UDI-SF, Urogenital Distress Inventory—Short Form; UUIE, urgency urinary incontinence episode.