Botox May Top Neuromodulation in Overactive Bladder

Diana Swift

October 06, 2016

Over the course of 6 months, a single injection of 200 units of onabotulinumtoxinA resulted in a small but statistically significant greater reduction in daily episodes of urgency urinary incontinence than sacral neuromodulation, according to a randomized study published in the October 4 issue of JAMA.

Use of twice the dose of the neurotoxin approved by the US Food and Drug Administration also led to greater patient-reported improvements on the Overactive Bladder Questionnaire Short Form questionnaire for symptom bother, as well as in treatment satisfaction and endorsement subscales.

However, the treatment was associated with higher risk for urinary tract infections and increased need for transient self-catheterizations, which raises questions about overall value of the treatment compared with sacral neuromodulation.

"Overall, these findings make it uncertain whether onabotulinumtoxinA provides a clinically important net benefit compared with sacral neuromodulation," write Cindy L. Amundsen, MD, a professor of obstetrics and gynecology urogynecology and reconstructive pelvic surgery at Duke University in Durham, North Carolina, and colleagues.

"But our study did not find the high urinary retention rates (that is, the need for catheterization) after injecting 200 units of botulinum toxin, as have been reported in previous studies using this dose. And while there is the risk of developing a [urinary tract infection] with injections, we were surprised that our rate using 200 units was no greater than studies using 100 units," Dr Amundsen told Medscape Medical News. "In addition, our study found no differences between the therapies in quality-of-life measures for adverse events or treatment convenience."

Dr Amundsen and associates conducted the open-label trial between February 2012 and January 2015 at nine sites in the National Institutes of Health–sponsored Pelvic Floor Disorders Network. They randomly assigned 364 women with refractory incontinence and a mean age of 63.0 years to cystoscopic intradetrusor injection at 200 units (n = 190) or implantation of a neuromodulator (n = 174).

Treatments Should Be Viewed as Complimentary, Expert Says

During the 6-month trial, onabotulinumtoxinA treatment resulted in an average of 3.9 fewer episodes of urgency incontinence per day compared with an average reduction of 3.3 episodes with sacral neuromodulation, which was the primary endpoint (mean difference, 0.63; 95% confidence interval [CI], 0.13 - 1.14; P = .01).

In other findings, among participants who completed at least four monthly diaries, 20% in the injection arm vs 4% in the neuromodulation group reported complete resolution of their incontinence, for a difference of −16% (95% CI, −26% to −5%; P < .001). In the injection group, 46% vs 26% in the neuromodulation group had at least a 75% reduction in the number of incontinence episodes, for a treatment difference of −20% (95% CI, −30% to −9%; P < .001).

In terms of adverse events, six women (3%) in the sacral neuromodulation group underwent revision or removal of their devices over the course of 6 months. In the onabotulinumtoxinA group, 8% required intermittent self-catheterization at month 1, 4% at month 3, and 2% at month 6. By 6 months, the cumulative incidence of urinary tract infections was higher with onabotulinumtoxinA, at 35% vs 11% (difference, −23%; 95% CI, −33% to −13%; P < .001).

"Based on this randomized study of severely affected women, in third-line therapies botulinum toxin and sacral neuromodulation, both reduced urgency urinary incontinent episodes," Dr Amundsen said. "We hope this study will help inform physicians and patients who are trying to make a decision between these two therapies, aligning the potential adverse events with differences in efficacy."

Commenting on the study, Victor W. Nitti, MD, a urogynecologist and professor at New York University Langone Medical Center in New York City, told Medscape Medical News, "I believe the data here need to be weighed with some caution and knowledge about the two treatments. The fact that they used twice the approved dose of Botox makes the study somewhat flawed in my opinion. Side effects, and in particular the need to catheterize, go up considerably when going from 100 to 200 units."

Still, Dr Nitti said, the injections did produce a significant difference vs neuromodulation in urinary incontinence episodes. "While it may not seem like 0.6 incontinence episodes per day is a big difference, when you look at it and a statistical model, it is. So I would say that's a positive for Botox."

He added that before these third-line therapies are used, physicians should recommend first-line treatments with behavioral modification, pelvic floor exercises, and physical therapy, followed, if necessary, by second-line treatment with medication.

In selecting a third-line therapy, the patient and her physician need to decide which treatment is best, on the basis of her specific characteristics, goals, and adverse effect tolerance level. "For example, the patient who is absolutely averse to catheterization would not be the best candidate for Botox," Dr Nitti said. "The patient who needs to have MRI studies for one reason or another would not be a good candidate for the implantation of a sacral neuromodulation device. These treatments should be viewed as complementary, not competitive."

Dr Amundsen added that although the initial costs for neuromodulation therapy are higher, patients who receive botulinum toxin may require additional injections for continuing treatment. "Our trial is following participants for 2 years in which cost analysis information will be evaluated as well as 2-year efficacy outcomes," she said.

The researchers reported the results of the trial at the American Urological Association (AUA) 2016 Annual Meeting in May.

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the Office of Research on Women's Health at the National Institutes of Health. One coauthor is the project scientist for the Pelvic Floor Disorders Network at the Eunice Kennedy Shriver National Institute of Child Health and Human Development and was involved in all aspects of the study. One coauthor reported receiving grant funds from Pfizer; another coauthor reported serving as a consultant for Medtronic, Allergan, and Axonics. Dr Nitti has performed research for Allergan.

JAMA. 2016;316:1366-1374. Abstract

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