Dr. Brubaker

Injections of botulinum toxin A, 200 U, provided adequate symptom control for refractory urge incontinence symptoms in approximately 60% of women treated. Time to failure was at least greater than 6 months (>193 days), versus ≤62 days for those given placebo.

"In addition to adequate symptom control in 60% of participants, we also found significant improvement in quality of life using validated measures," said Linda Brubaker, MD, professor of obstetrics/gynecology and urology at Loyola University Medical Center. "The duration of efficacy is important to understand in terms of finding out the role of repeat injections and cost effectiveness of a single injection."

Women in the study had refractory urge incontinence with at least six urge incontinence episodes in a 3-day diary. They also had documented detrusor overactivity incontinence in the preceding 12 months, and had experienced inadequate symptom control after undergoing at least two previous types of therapy.

The primary outcome was time to failure, defined as a Patient Global Impression of Improvement (PGI-I) score ≥4 ("inadequate improvement") at least 2 months post-injection, or as the start/increase of any detrusor overactivity treatment at any point following injection.

Concomitant retention halts Tx

"This was higher than previously reported in the literature," Dr. Brubaker said of the retention rate. "Perhaps this was because we actually checked this in all patients, as opposed to seeing if they had the traditional symptoms of retention. One of the most important findings in the study is that you cannot rely on the typical clinical symptoms of retention—you must check."

Dr. Brubaker defined retention as a post-void residual volume >200 mL regardless of symptoms at 4 weeks or catheterization. Most urinary retention found (75%) was determined by post-void residuals.

Diary-documented episodes of incontinence decreased significantly at 1 month post-injection in the botulinum toxin A group, from 17 to 3 for urge incontinence and from 21 to 4 for all types of incontinence. In contrast, decreases in the placebo cohort were much less significant.

Post-injection assessment included a telephone call at approximately 7 days after injection and a monthly assessment consisting of the Patient Global Impression of Improvement, Patient Global Symptom Control, and a 3-day urinary diary during the first month post-treatment only.

Dr. Brubaker is quick to note that this is still an off-label indication for botulinum toxin A, but high rates of efficacy in European case series of neurogenic patients, as well as reported clinical experience in idiopathic patients, helped plant the seeds for the trial.

"The botulinum injection is less frequent than a daily pill, which enhances compliance and, therefore, probably enhances symptom control," Dr. Brubaker said. "But the risk of retention and cost are both potential disadvantages."

Injection techniques were standardized in the study, with 6 cc of the masked substance injected into 15 to 20 different detrusor muscle sites under direct visualization, sparing the bladder trigone and ureteral orifices.

Allergan, Inc. supplied the botulinum toxin A for the study, but did not participate in its design, conduct, or analysis. The investigation was undertaken for the Pelvic Floor Disorders Network, whose work is funded by the National Institute of Child Health and Human Development.