New York—Repeated onabotulinumtoxinA 100 U (onabotA [Botox]) injections continue to provide benefit for patients with overactive bladder syndrome and urinary incontinence and without evidence of any new safety concerns, according to results of a pre-specified interim analysis in an open-label, 3-year extension study.
“The final, end-of-study complete dataset should be available soon. However, the messages from this third interim analysis are first, that the adverse events of onabotulinumtoxinA treatment for OAB syndrome with urinary incontinence have been well characterized, and second, that patients who start on this therapy and benefit can expect continued success with a consistent duration of response,” said co-author Victor W. Nitti, MD, professor of urology and obstetrics/gynecology, New York University Langone Medical Center, New York.
The analysis included data for 829 patients who entered the long-term study after completing one of two placebo-controlled phase III pivotal trials. To be eligible to participate in the phase III studies, patients had to have at least three urgency urinary incontinence (UI) episodes over 3 days, at least eight micturitions/day, and be inadequately managed with an anticholinergic agent. Repeat treatments were given at a minimum interval of 12 weeks upon patient request and if the patient was experiencing two or more urgency UI episodes/3 days and had a post-void residual volume <200 mL.
At the time of the interim analysis, median follow-up was 2.4 years and 544 patients had been followed at least 2 years. Numbers of patients receiving 2, 3, 4, and 5 treatment cycles were 580, 310, 178, and 104, respectively.
Outcomes were assessed at 12 weeks post-injection, and across all five treatment cycles, consistent benefits were observed in the co-primary endpoints of mean change from baseline in UI episodes/day (range, –3.2 to –3.9) and proportion of patients reporting a positive response (“greatly improved” or “improved”) on the Treatment Benefit Scale (range, 74% to 86%). There were also consistent mean reductions from baseline in micturition episodes/day (range, –2.4 to –2.9) and urgency episodes/day (range, –3.7 to –4.2). Median time to request for re-treatment was 24.0 weeks for cycle 1 and ranged from 23.9 to 31.6 weeks across cycles 2 to 5.
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Gains in QoL stable, clinically relevant
In addition, improvements in health-related quality of life assessed with the incontinence-quality of life instrument and the role limitations and social limitations domains of the King’s Health Questionnaire were stable and clinically relevant.
Dr. Nitti observed that findings from an interim analysis performed a year earlier showed the benefit of repeat treatment with onabotA was less dramatic after cycles 4 and 5 compared to after 1, 2, or 3 cycles. However, it was suspected at the time that the results were explained by the fact that relatively few patients had progressed to cycles 4 and 5, so that the patients experiencing a less dramatic and long-lasting response even from the outset of treatment were over-represented in the groups receiving 4 and 5 treatment cycles.
“Now, with a longer median follow-up, there is no longer evidence that the efficacy of onabotA is dwindling in cycles 4 and 5,” Dr. Nitti said.
There was no change in the types of adverse events reported over time. Urinary tract infection was the most common adverse event. Its incidence was 27.5% after the first treatment cycle and 18.2% after treatment cycle 5. The proportion of patients needing clean intermittent catheterization ranged from 2.9% to 4.6% across treatment cycles 1 to 5, and for the entire cohort, there were low rates of patient withdrawal for reasons of lack of efficacy (4.9%) or adverse events (4.5%).
“It is currently unclear if the drop-off in UTI incidence represents anything clinically significant, but it does seem that the risk of needing intermittent catheterization is about the same whether patients are having their first injection or repeated treatment up to 5 cycles,” Dr. Nitti said.
Findings from the study were presented at the AUA annual meeting in Orlando, FL and the European Association of Urology annual congress in Stockholm, Sweden.
Dr. Nitti has consulted for and been an investigator in studies funded by Allergan. Study co-authors have served as consultants/advisers, meeting participants/lecturers, and/or investigators or are employees of Allergan.