WASHINGTON, DC — Repeat treatments with onabotulinumtoxinA (Botox, Allergan) continue to improve symptoms of overactive bladder for a median of 2.4 years in women with urinary incontinence, a new study finds.
The interim analysis of a prospective extension study of 749 women previously enrolled in 12-week trials also identified no new safety signals from long-term repeated Botox use. The data were presented here at the American Urogynecologic Society and International Urogynecological Association (IUGA) 2014 Scientific Meeting.
“This is the first longitudinal study clearly showing that onabotulinumtoxinA is maintaining its efficacy over time, even after several injections, with very few side effects,” said presenter Tomasz Rechberger, MD, head of the Department of Gynecology at the Medical University of Lublin in Poland.
“The main message is that onabotulinumtoxinA is extremely effective, even in patients in whom classical treatment was a complete failure,” he told Medscape Medical News.
Botox was approved in 2013 by the US Food and Drug Administration for the treatment of overactive bladder to reduce urinary incontinence in patients who don’t respond to anticholinergics or can’t use them. The approval was based on data from 2 large randomized placebo-controlled phase 3 trials, each lasting 12 weeks.
OnabotulinumtoxinA is extremely effective, even in patients in whom classical treatment was a complete failure.
“We know that overactive bladder is a chronic condition,” said IUGA president G. Willy Davila, MD. “With treatments that are restricted in their effectiveness in time, like Botox, which works for 6 months, it’s nice to know that if you treat someone again and again and again, it’s going to keep working and it’s not going to cause more side effects,” he told Medscape Medical News.
However, Dr. Davila, who was not involved in the study, cautioned that some data suggest that there is a limit to the efficacy of Botox beyond 5 years. “We just need to keep doing more research to see what happens on an even longer-term basis,” he explained.
The multicenter, multinational, open-label extension study is following patients for up to 3 years using a Botox dose of 100 U. It is scheduled to run until August. The interim analysis presented by Dr. Rechberger involved data up to June 2013.
All 749 women in the study had 3 or more urinary urgency incontinence episodes noted in a 3-day diary, 8 or more micturitions a day, and were inadequately managed with anticholinergics.
The number of Botox treatments varied by patient. Prespecified criteria for retreatment were patient request, an interval of at least 12 weeks from the previous treatment, 2 or more incontinence episodes within 3 days, and a postvoid residual urine volume below 200 mL.
Each treatment comprised 20 cystoscopic 0.5 mL injections. Prophylactic antibiotics (ciprofloxacin) were given for 3 consecutive days after injection.
The mean age of the women was 60 years, and the mean time since overactive bladder diagnosis was 6.4 years. Just over a third (37%) discontinued the study, but only about 4% discontinued because of adverse events or lack of efficacy, Dr. Rechberger reported.
The investigators found that the number of incontinence and urgency episodes declined with treatment.
Table. Outcomes With Botox Treatment
|Outcome||Episodes per Day|
|Daily incontinence episodes|
|After 3 treatments||3.9|
|After 4 treatments||3.2|
|Daily urgency episodes|
|After 3 treatments||4.2|
|After 4 treatments||3.6|
Consistent improvements were also seen in micturition frequency (about 2.5 fewer per day) and volume (about 55 mL more per day) with the repeat Botox treatments, Dr. Rechberger reported.
For more than three-quarters of the women, median treatment effect duration was at least 6 months, he noted.
Urinary tract infection was the most common adverse event but declined slightly with each treatment, from 29.6% after treatment 1 to 19.5% after treatment 5. Bacteriuria decreased from about 8.0% to 6.3% after treatment 5.
The rate of urinary retention remained consistently low over the treatment cycles (2.3% to 3.7%), as did the rate of patient initiation of clean intermittent catheterization (3.1% to 4.5%).
Despite the positive results, Botox will remain second-line therapy until more data can be collected, Dr. Rechberger told Medscape Medical News.
“Botox is definitely second-line treatment after lifestyle changes and pharmacotherapy,” he explained, “but its usage is increasing mainly because of high clinical effectiveness.”
Dr. Rechberger acknowledged that the need for cystoscopic injection could be a limitation to wider Botox use. “It is simple, but still you need cystoscopic equipment and you have to be familiar with the technique, which is a bit more complicated than pill-taking.”
Although Botox will remain the second-line treatment, “doctors should be aware of its potential for patients who are not happy with either anticholinergics or beta-3 mimetics.”
“It’s not ready to become first-line yet, but I think as time goes on and we look at the effectiveness and cost/benefit ratio of different therapies, this might become first-line for some patients, possibly based on severity or neurologic predisposing condition,” Dr. Davila told Medscape Medical News.
This study is funded by Allergan. Dr. Rechberger consults for Allergan, Astellas, and Johnson & Johnson. Dr. Davila has received research funding for an anticholinergic manufactured by Pfizer.
American Urogynecologic Society (AUGS) and International Urogynecological Association (IUGA) 2014 Scientific Meeting. Abstract PP-04. Presented July 23, 2014.
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