OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial

Abstract

Importance: Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information.

Objective: To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence.

Design, setting, and participants: Multicenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence.

Interventions: Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189).

Main outcomes and measures: Primary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events.

Results: Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%.

Conclusions and relevance: Among women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.

Figure 1. Flow Diagram of Progress Through Phases of a Randomized Trial Comparing OnabotulinumtoxinA With Sacral Neuromodulation Among Women With Refractory Urgency Urinary Incontinence

^aReceipt of treatment as assigned per protocol for onabotulinumtoxinA includes complete first injection of 200 U and for sacral neuromodulation includes attempting the first-stage lead placement and if successful, continuing on to second-stage surgery: implantable pulse generator (IPG) implant for clinical responders and lead removal for nonresponders. Clinical response was defined as 50% or more reduction in mean episodes of urgency urinary incontinence on a 3-day bladder diary during the 7- to 14-day testing phase. ^bThrough treatment phase includes all randomized individuals who continued the study through the treatment phase into study follow-up irrespective of whether they started or completed the assigned study treatment. ^cFive baseline diaries were identified as being invalid during a data quality audit that occurred after randomization. All 5 individuals were treated and included in safety analyses but excluded from all analyses of efficacy.

Figure 2. Change From Baseline in Urgency Urinary Incontinence Episodes per Day by Treatment Group by Month

Values in the graph include adjusted mean estimates and associated 95% CIs (indicated by error bars) obtained from the linear mixed model controlling for randomization strata defined by age group (<65 years vs ≥65 years) and site. The number of diaries for each treatment group and month included in the model varies from 151 to 179 for the intention-to-treat population and 122 to 154 for the clinical responder population, but all values from all time points contribute to the mean and interval estimates at each time point. A clinical responder is defined as having 50% or more reduction in mean number of episodes of urgency urinary incontinence on a 3-day bladder diary duringthe 7- to 14-day testing phase for women randomized to receive sacral neuromodulation and 1 month after injection for women randomized to receive onabotulinumtoxinA.