Anticholinergic therapy and onabotulinumtoxinA produce equivalent reductions in the frequency of daily UUI episodes
Visco AG, Brubaker L, Richter HE, et al; for the Pelvic Floor Disorders Network. Anticholinergic therapy vs onabotulinumtoxinA for urgency urinary incontinence. N Engl J Med. 2012;367(19):1803-1813.
In a double-blind, double-placebo-controlled randomized trial, Visco and colleagues compared anticholinergic medication with onabotulinumtoxinA 100 U for the treatment of women with UUI.
Details of the study
Two hundred forty-one women with moderate to severe UUI received either 6 months of oral anticholinergic therapy (solifenacin 5 mg daily with the option of dose escalation to 10 mg daily or change to trospium XR 60 mg daily based on the Patient Global Symptom Control score) plus a single intradetrusor injection of saline, or a single intradetrusor injection of onabotulinumtoxinA 100 U plus a 6-month oral placebo regimen.
Inclusion criteria were 5 or more UUI episodes on a 3-day diary, insufficient resolution of symptoms after 2 medications, or being drug naive. Exclusions included a postvoid residual (PVR) urine volume greater than 150 mL or previous therapy with onabotulinumtoxinA.
Participants were scheduled for follow up every 2 to 6 months post randomization, at which time all study medications were discontinued. The primary outcome was reduction from baseline in the mean number of UUI episodes per day over the 6-month period, as recorded in the monthly 3-day bladder diaries. Secondary outcomes included the proportion of participants with complete resolution of UUI, the proportion of participants with 75% or more reduction in UUI episodes, Overactive Bladder Questionnaire Short Form (OABq-SF) scores, other symptom-specific questionnaire scores, and adverse events.
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Both treatments significantly reduced UUI episodes
At baseline, participants reported a mean (SD) of 5.0 (2.7) UUI episodes per day, and 41% of participants were drug naive. Both treatment groups experienced significant reductions compared with baseline in mean UUI episodes, and the reductions were similar between the 2 groups (reduction of 3.4 episodes per day in the anticholinergic group, reduction of 3.3 episodes in the onabotulinumtoxinA group; P = .81). Complete resolution of UUI was more common in the onabotulinumtoxinA group (27%) as compared with the anticholinergic group (13%) (P = .003). There were no differences in improvement in OABq-SF scores (37.05 in the anticholinergic group vs 37.13 in the onabotulinumtoxinA group; P = .98) or other quality-of-life measures.
Adverse events. The anticholinergic group experienced a higher rate of dry mouth compared with the onabotulinumtoxinA group (46% vs 31%; P = .02) but had lower rates of intermittent catheterization use at 2 months (0% vs 5%, P = .01) and UTIs (13% vs 33%, P<.001).
Strengths and limitations. This was a well-designed, multicenter, randomized double-blind, double placebo-controlled trial. The study design allowed for dose escalation and change to another medication for inadequate symptom control and included drug-naive participants, which increases the generalizability of the results. However, current guidelines recommend reserving onabotulinumtoxinA therapy for third-line therapy, thus deterring this treatment's use in the drug-naive population. Additionally, the lack of a pure placebo arm makes it difficult to interpret the extent to which a placebo effect contributed to observed improvements in clinical symptoms.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Through 6 months, both a single intradetrusor injection of onabotulinumtoxinA 100 U and anticholinergic therapy reduce UUI episodes and improve quality-of-life measures in women who have failed medications or are drug naive. Use of onabotulinumtoxinA, however, more likely will lead to complete resolution of UUI, although with an increased risk of transient urinary retention and UTI. Even given the study findings supporting the use of onabotulinumtoxinA over anticholinergic therapy for complete resolution of UUI, it is most appropriate to align with current practice, which includes a trial of pharmacotherapy before proceeding with third-line onabotulinumtoxinA.