Overactive Bladder Symptoms Improved With Botox Injections

October 9, 2012 (Chicago, Illinois) — Oral anticholinergic therapy and intradetrusor onabotulinumtoxinA (Botox) injection result in similarly significant improvements in daily urinary incontinence episodes. Both treatments also improved symptom-specific quality of life, with no significant between-group differences.

Anthony G. Visco, MD, from Duke University Medical Center in Durham, North Carolina presented results from a double-blind randomized trial here at the American Urogynecologic Society 33rd Annual Scientific Meeting. The results were also published online October 4 in the New England Journal of Medicine.

Women with idiopathic urgency urinary incontinence who had 5 or more episodes of urgency over a 3-day period were eligible for the trial. Of 247 women treated, 241 completed the study.

Participants were randomly assigned to 1 of 2 treatment groups: a standardized 6-month regimen of oral anticholinergic medication (solifenacin 5 mg each day with a possible increase to 10 mg and, if necessary, a subsequent switch to extended-release trospium 60 mg) plus 1 intradetrusor injection of saline; or 1 intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo.

At baseline, the average number of episodes of urinary incontinence each day was 5.0; this decreased to 3.4 in the anticholinergic group and to 3.3 in the onabotulinumtoxinA group (P = .81).

A complete resolution of urgency urinary incontinence was more common in the onabotulinumtoxinA group than in the anticholinergic group (27% vs 13%; P = .003). In addition, women in the onabotulinumtoxinA group were less likely to have dry mouth than those in the anticholinergic group (31% vs 46%; P = .02).

Transient Urinary Retention

However, there were higher rates of catheter use in the onabotulinumtoxinA group than in the anticholinergic group (5% vs 0%; P = .01), and more urinary tract infections (33% vs 13%; P < .001).

"We were concerned that the efficacy of onabotulinumtoxinA might be counteracted by the side effect of urinary retention; we had stopped a previous placebo-controlled trial of onabotulinumtoxinA at a dose of 200 U early because the rate of urinary retention was 43%" (J Urol. 2008;180:217-222), Dr. Visco and colleagues write. It is because of this concern that the lower dose (100 U) was chosen for this trial.

John O. DeLancey, MD, professor of obstetrics and gynecology at the University of Michigan in Ann Arbor, spoke with Medscape Medical News about the study: "It was an extremely well-done study.... It is really exciting that we finally have actual data."

In a previous review of 61 trials (Cochrane Database Syst Rev. 2006;4:CD003781), anticholinergic therapy resulted in 0.54 fewer episodes of urinary incontinence per day in the anticholinergic group than in the placebo group. In other trials, anticholinergic therapy has demonstrated robust efficacy in the treatment of urgency urinary incontinence, according to the authors. However, anticholinergic drugs are associated with a high rate of adverse effects and poor long-term adherence.

Dr. Visco spoke with Medscape Medical News about his team's study and concluded that both anticholinergics and intradetrusor onabotulinumtoxinA injections "are reasonable options." They suggest that physicians base their decision of which of these 2 therapies to use on the routes of administration and adverse-effect profiles.

OnabotulinumtoxinA is currently approved by the US Food and Drug Administration (FDA) "to treat urinary incontinence in people with neurologic conditions such as spinal cord injury and multiple sclerosis who have overactivity of the bladder." A broader urinary incontinence indication is currently being reviewed by the FDA.

"This is the first randomized controlled clinical trial that directly compared onabotulinumtoxinA with anticholinergic medications in women with predominant idiopathic urgency urinary incontinence," Tatyana Shamliyan, MD, from the University of Minnesota School of Public Health in Minneapolis, told Medscape Medical News. Dr. Shamliyan was not involved in the study.

"The study demonstrated similar effects with examined treatments on frequency of the daily episodes of urgency urinary incontinence and on quality-of-life measures," Dr. Shamliyan said. However, more women had a complete resolution of incontinence with onabotulinumtoxinA injections than with drugs.

According to Dr. Shamliyan, women should be informed about efficacy and adverse effects related to both treatment options. "Treatment choice should be based on the tolerability of the previous drug treatments and increased risks of intermittent catheterization and urinary tract infection with onabotulinumtoxinA injections," she added.

Dr. Shamliyan pointed out that a single randomized controlled trial provides only a low strength of evidence about comparative effectiveness and safety between a single dose of onabotulinumtoxinA and anticholinergic drugs.

"Future randomized controlled trials are needed to provide consistent precise estimates of continence and clinically meaningful improvement in quality of life for women with frequent predominant urgency urinary incontinence," she said. "Subgroup analyses of baseline frequency, comorbidities, and risk factors for urinary incontinence, as well as prior treatment response, should provide the evidence for individualized treatment decisions."

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the National Institutes of Health Office of Research on Women's Health. Several coauthors report financial relationships with 1 or more of the following companies: Astellas Pharma, GlaxoSmithKline, Uromedica, IDEO, Pfizer, Xanodyne Pharmaceuticals, Pelvalon, Warner Chilcott, Pfizer, Ethicon, Ferring Pharmaceuticals, Cadence, and McGraw-Hill. Dr. Visco, Dr. DeLancey, and Dr. Shamliyan have disclosed no relevant financial relationships.

N Engl J Med. Published online October 4, 2012. Full text

American Urogynecologic Society (AUGS) 33rd Annual Scientific Meeting: Paper presentation 4. Presented October 3, 2012.