Repeat intradetrusor injections of onabotulinumtoxinA (Botox) are associated with sustained efficacy and no new safety signals.
Atlanta-Repeat intradetrusor injections of onabotulinumtoxinA (Botox) are associated with sustained efficacy and no new safety signals, long-term study results show.
The two placebo-controlled, double-blind studies randomized 691 patients. After 12 months, 397 patients continued into the extension phase. Their mean number of weekly UI episodes at baseline was ~31, reported study investigator Michael Kennelly, MD, at the AUA annual meeting in Atlanta.
Change from baseline weekly UI episodes at 6 weeks after injection was analyzed as the primary endpoint of interest and showed that repeat treatments resulted in consistent reductions across all cycles, with the mean changes for cycles one to five ranging from –22.7 to –31.9 for the 200-U group and from –23.6 to –29.5 for patients receiving the 300-U dose.
At 6 weeks after one to five repeat treatments with either onabotulinumtoxinA dose, between 73% and 94% of patients had achieved at least a 50% reduction from their baseline number of weekly UI episodes and between 36% and 55% of patients had no UI episodes. Mean volume per void remained consistently increased regardless of the number of retreatments. Considering the data for cycles one and two for which patient follow-up is most complete, the duration of effect (mean time to request for repeat treatment) was about 250 days, reported Dr. Kennelly, clinical professor of urology, University of North Carolina, Chapel Hill, and director of the Carolinas Medical Center's Charlotte Continence Center in Charlotte, NC.
Quality of life improvement, as measured with the Incontinence-QOL questionnaire, also remained statistically and clinically significant throughout the available follow-up. Across the five cycles, between 66% and 93% of patients had an improvement from baseline ≥11 points, which defines a minimally important difference.
Safety profile unchanged
The safety profile of onabotulinumtoxinA detrusor injections was unchanged relative to during the controlled portion of the pivotal trials. Urinary tract infection and urinary retention, which were diagnosed based on the investigator's judgment, remained the most common adverse events with both doses, and their incidence did not change over time.
"Clinicians are concerned about the effects of long-term onabotA treatment, and it is useful to have evidence from these large multicenter clinical trials," said Dr. Kennelly.
"So far, the results indicate onabotA continues to be effective with repeated injections and the safety data do not raise any signals about long-term adverse events. However, this is an interim analysis and results from longer follow-up will be clearly important for urologists around the world who are using onabotA to manage UI in patients with neurogenic detrusor overactivity."
Dr. Kennelly is a consultant/adviser for Allergan, Inc., Astellas Pharma Inc., Pfizer Inc., and Watson Pharmaceuticals, Inc. His co-authors are consultant/advisers, investigators, meeting participant/lecturers, and/or employees of Allergan.