AT THE AUA ANNUAL MEETING
NEW ORLEANS (FRONTLINE MEDICAL NEWS) – Long-term treatment with botulinum toxin type A significantly decreased daily urinary incontinence episodes in patients with overactive bladder syndrome, with no increase in adverse effects tied to repeated treatment, according to Dr. Victor W. Nitti.
Dr. Nitti and his colleagues conducted a multicenter extension study evaluating the long-term efficacy and safety of repeated treatments with botulinum toxin type A (BTX-A, also known as Botox) in patients with overactive bladder (OAB).
After completion of either of two 24-week, randomized phase III trials, patients were eligible to enter a 3-year extension study in which they could receive multiple BTX-A treatments at 100 units per dose, Dr Nitti reported at the annual meeting of the American Urological Association.
Patients were treated “as needed” based on their request, and their fulfillment of the prespecified qualification criteria. “Patients requesting treatment had to have at least two urgency incontinence episodes in a 3-day diary, at least 12 weeks since their last treatment, and their postvoid residual had to be less than 200 cc,” said Dr. Nitti, professor of urology at New York University, New York. Therefore, the total number of treatments delivered during the study differed among patients depending on need.
Coprimary endpoints included change from baseline in urinary incontinence episodes per day at week 12 and the proportion of patients reporting improvement or great improvement in their urinary incontinence (UI) at 12 weeks. Data were assessed for six subpopulations of patients based on the number of BTX-A treatments (one to six) needed during the study; duration of effect (time to request for retreatment) in all six cycles also was evaluated in order to assess the consistency of response to repeated treatments.
Local anesthesia was administered to patients, and BTX-A was delivered via injection into the muscle of the bladder. “Once the botulinum toxin gets into the terminal nerve, it will prevent the release of neurotransmitters, particularly acetylcholine; when acetylcholine is not released, there is less of a trigger for the bladder to contract,” he explained.
Of the 829 patients enrolled, 51.7% completed the 3-year study. About 5% did not complete the study because of an adverse event, and only 5.7% dropped out because of a lack of efficacy. “Over the 31/2-year period, patients were lost to follow-up, had protocol violations, and sites closed. So most of the reasons for discontinuation weren’t due to lack of efficacy or adverse events,” Dr. Nitti said.
The baseline mean UI episodes per day was a little over 5.5 for all treatment cycles; consistent reductions in UI episodes were observed in the overall population results regardless of the number of treatments received, with overall reduction between 3.1 and 3.8 episodes per day.
“Also consistent was the number of patients who reported being greatly improved or improved on the treatment benefit scale, which remained at right around 80% regardless of treatment cycle,” he added.
Patients who received fewer treatments had a longer duration of effect than those who received more treatments. The overall median duration of effect was 7.6 months, and 34.2% of the patients reported control of their urinary incontinence symptoms for at least 6 months. The median time to request retreatment was >6 to ≤12 months for 37.2%, and >12 months for 28.5% of patients. Urinary tract infection was the most common adverse event observed.
Based on these data, Dr. Nitti and his colleagues concluded that long-term treatment of OAB with BTX-A resulted in decreased daily urinary incontinence episodes, with no increase in adverse events tied to recurrent treatment.
Dr. Nitti disclosed financial relationships with Allergan, and numerous other pharmaceutical and device companies.