In this randomized, double-blind, comparative-effectiveness study, a standardized 6-month regimen of anticholinergic therapy and a single injection of 100 U of onabotulinumtoxinA each significantly reduced the number of daily episodes of urgency urinary incontinence; the magnitude of the reductions did not differ significantly between the treatments. Participants who received onabotulinumtoxinA, as compared with those who received anticholinergic therapy, more often had complete resolution of urgency urinary incontinence, whereas improvements in measures of quality of life did not differ significantly between the groups. The two treatments differ with respect to the method of administration: onabotulinumtoxinA is injected into the detrusor muscle by means of a cystoscopic procedure performed in a doctor’s office, whereas anticholinergic therapy involves daily oral intake of pills prescribed by a physician. Side effects also differ. The frequency of dry mouth was higher in the anticholinergic group, whereas the frequencies of incomplete bladder emptying requiring catheterization and urinary tract infections were higher in the onabotulinumtoxinA group.
Although placebo-controlled, randomized trials have shown the efficacy of anticholinergic medications in treating urgency urinary incontinence, the high rate of side effects and poor long-term adherence associated with them limit their use in practice for some patients who have urgency urinary incontinence.14–18
The rates of dry mouth in both groups in the current trial were higher than those reported in a Cochrane review,19
in which 31% of women taking anticholinergic agents and 10% of those taking placebo reported dry mouth. However, dry mouth was not a major cause of drug withdrawal — a finding similar to that in the Cochrane review — suggesting that the annoyance caused by this side effect is slight.
We were concerned that the efficacy of onabotulinumtoxinA might be counteracted by the side effect of urinary retention; we had stopped a previous placebo-controlled trial of onabotulinumtoxinA at a dose of 200 U early because the rate of urinary retention was 43%.3
For the current study, we chose a lower dose of onabotulinumtoxinA — 100 U, a dose that was associated with an 18% risk of urinary retention (defined as a residual volume after voiding of >200 ml) and an 11% risk of intermittent catheterization in a recent dose-finding study.20
We observed a lower rate of catheterization than this according to prespecified criteria in our study. However, additional off-protocol catheterizations were performed in both groups, perhaps in part because we warned the participants of the potential for urinary retention. Our results indicate that a 100-U dose of onabotulinumtoxinA is effective and has manageable side effects in this population of women with urgency urinary incontinence and without known neurologic conditions. Further study is needed to determine whether a higher dose of onabotulinumtoxinA would be appropriate for women with urgency urinary incontinence that is more severe than that in the women in our study or that is refractory to other therapy.
In the Cochrane review,19
which encompassed 61 trials, the mean reduction in episodes of urgency urinary incontinence per day ranged from 0.6 to 1.7 among people receiving anticholinergic medications and between 0.1 and 1.9 among those receiving placebo, with 0.54 fewer episodes per day among participants receiving the anticholinergic medications than among those receiving placebo. The greater reduction in episodes observed in both groups in our study may be due to the higher baseline severity in our population.
We chose the oral medications for this trial on the basis of several considerations, including the option for dose escalation of the initial drug and, if necessary, a switch to a second drug that had mechanisms of action different from the first but that was administered in the same way (orally, once daily). Solifenacin is a relatively selective M3 antagonist, and trospium has nonselective muscarinic activity, had recently become available in once-daily dosing, and has been associated with a low rate of dry mouth (8.7%).6
Although it is uncertain whether our results are generalizable to other anticholinergic drugs, systematic reviews report few clinically significant differences among currently available anticholinergic drugs.2
The randomized, controlled design that includes two active-treatment groups and an effective double-blind procedure improves our ability to interpret our primary comparison. The inclusion of participants who had not had prior exposure to anticholinergic medications as well as those who had had prior exposure to up to two anticholinergic medications, the inclusion in the study of participants from multiple sites, and the broad eligibility criteria facilitate the generalizability of our study findings. Since we studied a single injection of one formulation of botulinum toxin A (onabotulinumtoxinA at a dose of 100 U), we are unable to comment on the safety or efficacy of other botulinum toxin preparations or on effects of multiple injections of onabotulinumtoxinA as compared with longer-term anticholinergic therapy. Prior studies have shown that effectiveness is maintained after multiple injections of onabotulinumtoxinA into the detrusor muscle and that the mean interval between injections (265 days) is not reduced with repeated injections.21,22
Since our trial compared two active treatments, we cannot determine to what extent the observed improvements reflect a placebo effect. However, the observed rates of cure or improvement observed in our study exceed the placebo effect observed in trials of anticholinergic drugs.19
Further research is needed to compare patient adherence and the cost-effectiveness of these two therapeutic approaches.
In summary, we found that among women with urgency urinary incontinence, there was no significant difference between anticholinergic drugs and onabotulinumtoxinA by injection on the reduction of the frequency of episodes of urgency incontinence or improvements in quality of life. The choice between these therapies should take into account the differing regimens and routes of administration and the side-effect profiles, including more frequent occurrence of dry mouth with anticholinergic medication and higher risks of intermittent catheterization and urinary tract infection with onabotulinumtoxinA.