Study questions botulinum’s efficacy in post-BPH overactive bladder

New York-Intradetrusor injections of onabotulinumtoxinA (Botox) do not significantly reduce urinary frequency in patients with refractory overactive bladder secondary to BPH, results from a two-institution, placebo-controlled study indicate.

The phase III randomized, double-blind study included 28 patients with OAB secondary to BPH. OAB was refractory to anticholinergic medication and persistent after surgical intervention to relieve obstruction, with an International Prostate Symptom Score (IPSS) >12.

Patients were randomized to 20 injections of intradetrusor onabotulinumtoxinA, 10 U (15 patients) or placebo (13 patients). Follow-up was performed at 1 week and then at 1, 3, 6, and 9 months. Voiding diaries, maximum flow rate (Qmax), post-void residuals (PVR), and IPSS scores were reviewed. The primary endpoint was frequency of micturition, with PVR; IPSS and Qmax were secondary endpoints.

Baseline characteristics were similar between the treatment groups, with the exception of body mass index, which was higher in the placebo group (32.5 vs. 25.7, p=.02). The median baseline IPSS was 16 in those assigned to onabotulinumtoxinA and 20 in the placebo group, the median baseline Qmax was 21.1 mL/s in the onabotulinumtoxinA group and 16.0 mL/s in the placebo group, and the median PVR at baseline was 38.3 mL and 34.8 mL, respectively. The median voiding frequency pre-procedure was 11.0 versus 10.5 in the onabotulinumtoxinA and placebo groups, respectively.

“For this cohort, there were no significant differences in the change in urinary frequency,” said first author Daniel J. Lee, MD, a urology resident at Weill Cornell Medical College, New York.

“There were significant differences in the change in quality of life, which means that the subjective experience of bother from the urinary frequency was significantly improved in those who had botulinum toxin versus placebo,” added Dr. Lee, who worked on the study with Alexis Te, MD, colleagues.

No significant change in urinary frequency

At day 180, the change in daily urinary frequency from baseline was –3.5 events in the onabotulinumtoxinA group and 0 in the placebo group, which did not achieve significance (p=.19), the researchers reported at the 2012 AUA annual meeting in Atlanta. At follow-up day 270, patients assigned to onabotulinumtoxinA had four fewer events compared with baseline versus one fewer event in the placebo recipients, which again was not significant (p=.51).

At both days 180 and 270, urinary urgency declined from baseline by one event in the onabotulinumtoxinA group compared with three events in the placebo group.

The quality of life score declined by only 1.5 points from baseline to day 180 in the onabotulinumtoxinA group compared with 11 points the placebo group (p=.02). By day 270, the quality of life score improved by three points from baseline in the onabotulinumtoxinA group but decreased by 12.5 points in the placebo group, which was again significant (p=.03).

There was no difference in the change in the International Consultation on Incontinence Questionnaire score from baseline between groups at day 180, but at day 270, those assigned to onabotulinumtoxinA had an improvement of 8.5 points compared with an improvement of four points in the placebo group (p=.03).

There were no significant differences between groups in the changes in PVR, Qmax, or IPSS at either day 180 or day 270.

Patients receiving onabotulinumtoxinA demonstrated higher Qmax compared to placebo at the 90-day follow-up. Urinary frequency, IPSS, and PVR were unchanged postoperatively in both groups.

“This is a very different patient cohort than those with idiopathic OAB. Their overactive bladder is secondary to some obstruction that was treated before entry into the study,” Dr. Lee told Urology Times. “I think [botulinum toxin] is something that still needs to be looked at just because for these patients, there are no good treatments out there. Whether we need to change the location of the Botox injections-for this study, they were all above the trigone-or the frequency of injections (more than one time), especially in light of the 28 trials with Botox in idiopathic OAB… this is something that should still be investigated.”