Botulinum toxin shows efficacy in detrusor overactivity

Findings from the 60-week, randomized, controlled trial showed that botulinum toxin A (Botox) injected into the detrusor is not only well tolerated by patients, but provides beneficial improvements for up to 9 months.

For the most part, patients in the study group were already on intermittent catheterization or antimuscarinics going into the trial, but with limited success and inhibiting side effects. The goal, according to the research team, was to decrease leakage episodes for this patient population and improve their quality of life.

"We accomplished that, and the payoff was that it made a substantial difference in the quality of life of many of these patients."

Fifty-seven subjects-34 men and 23 women, ages 20 to 77 years-were recruited to participate in the prospective, double-blind, multicenter study. Patients were randomized to either botulinum toxin A, 300 units injected into 30 sites in the detrusor (sparing the trigone), or placebo.

"We used 1 cc dilution per injection, having decided to go for the highest dose known at the time, as we were looking for maximal efficacy versus the placebo," Dr. Herschorn noted.

Long-term improvement

The primary outcome measures, which were met, were changes in incontinence episodes and urodynamic parameters at 6 weeks. The botulinum toxin A group demonstrated significant improvements over the placebo group, most notably frequency of incontinence episodes and volume at first detrusor contraction. These improvements persisted in some cases for up to 36 weeks.

At 36 weeks, all patients entered an open-label phase and were given another 300 units of botulinum toxin A. When comparing voiding diaries, patient-reported outcomes, and validated questionnaires, subsequent evaluations of the full group at 48 and 60 weeks demonstrated significant improvements over baseline values in such measures as frequency of leakage episodes and impact of urinary leakage on everyday life.

The team found some tail-off over time as well as dissipation of effect, so future studies will include seeking effective long-term solutions that take patients beyond 36 or 60 weeks.

"This trial represents an off-label use of this drug," Dr. Herschorn pointed out. "Most previous studies have been independent of industry support, but this was an investigator-initiated trial and funded by Allergan. Now we face the issue of the drug being approved by regulatory bodies and then covered.

"Since industry-sponsored large-scale trials are still ongoing, it will probably take another few years before these processes are completed. However, because of the good response that patients in our study and in similar studies have experienced, we are facing a significant demand for this drug among our patient population."