“Bladder leakage is a very common condition that can seriously diminish a person’s quality of life,” said Anthony G. Visco, M.D., lead author of the study and chief of Duke’s Urogynecology and Reconstructive Pelvic Surgery Division. “The first line of treatment is often oral medications, but these can have bothersome side effects that cause people to quit taking them. There is a strong need for additional options.”
Urinary incontinence results from unpredictable activity of the bladder muscles. The cause is often unknown, but the condition affects up to one in five older women in the United States. Injections of onabotulinumtoxin-A, known widely as Botox, relax the overactive bladder muscles.
Currently approved by the U.S. Food and Drug Administration for urinary incontinence resulting from spinal cord or other neurological injuries, Botox injections have been gaining popularity among doctors and patients as an “off-label” treatment for the more common overactive bladder condition.
To see how Botox compared to current therapies, the Duke-led researchers enrolled nearly 250 women at 10 medical centers across the country. The women suffered from moderate to severe bladder incontinence, averaging five bladder leakage episodes a day.
The women were randomly assigned to one of two groups. One group received Botox injections in the bladder muscle along with six months of placebo pills. The other received six months of anticholinergic medications and a bladder injection of harmless saline. Neither the women nor their doctors knew who received which treatment.
Regular checkups occurred every two months. All patients who were assigned to oral medication were started on a low dose of solifenacin and could increase to a higher dose if symptoms were not adequately controlled at 2 months. At the 4-month mark, patients had the option of changing to trospium XR. All pills were stopped at six months.
At the end of the active treatment phase, 70 percent of women reported adequate symptom control; women in both groups reporting an average of three fewer leakage episodes a day. Within one month after discontinuation of the oral regimen, significantly fewer women assigned to the pill therapy reported adequate symptom control compared to the injection group – 50 percent vs. 62 percent.
At 12 months, 25 percent of the anticholinergic group and 38 percent of the Botox group reported continued adequate control. Women in the injection group were also twice as likely as those taking daily pills to report complete resolution of the problem – 27 percent vs. 13 percent.
Both treatments had side effects. The pills, which act on smooth muscles that include the salivary glands, caused dry mouth more frequently, and Botox injections resulted in more catheterizations and urinary tract infections.
“This study has the potential to change how patients with urinary incontinence are treated,” Visco said, adding that the FDA would first have to expand its approval of Botox injections for urge incontinence to include overactive bladder even when the underlying cause is unknown. This would likely need to occur before the treatment could be covered by insurance.
“Patients need more choices than they have had up to now — would they rather take a pill for an indefinite period of time, or come in to the doctor’s office and have an injection about once a year? Both have their benefits and their side effects, but having more choices for women would be a great improvement,” Visco said.
In addition to Visco, study authors in the Pelvic Floor Disorders Network include: Linda Brubaker, Loyola University; Holly E. Richter, University of Alabama at Birmingham; Ingrid Nygaard, University of Utah; Marie Fidela R. Paraiso, Cleveland Clinic; Shawn A. Menefee, Kaiser Permanente San Diego; Joseph Schaffer, University of Texas Southwestern Medical Center; Jerry Lowder, University of Pitttsburgh; Salil S. Khandwala, Oakwood Hospital & Medical Center; Larry Sirls, Beaumont Health System; Cathie Spino, University of Michigan; Tracy Nolen and Dennis Wallace, RTI International; Susan F. Meikle, National Institutes of Health.
The study was supported by grants from The Eunice Kennedy Shriver National Institute of Child Health and Human Development, (Duke: 2-U10-HD04267-12, Loyola: U10-HD054136, UAB: 2-U10-HD041261-11, Utah: U10-HD041250, Cleveland Clinic: 2-U10-HD054215-06, UCSD: 2-U10-HD054214-06, Pittsburgh: 1-U10-HD069006-01, UTSW: 2-U10-HD054241-06, Univ. of Michigan: U01-HD41249, RTI: 1-U01-HD069010-01) and the NIH Office of Research on Women’s Health.
Botox and pills for overactive bladder show similar effect
The study, funded by the National Institutes of Health, is the first head-to-head comparison of Botox and anti-cholinergic drugs. The findings were published in the Oct. 4, 2012, issue of the New England Journal of Medicine and presented at the annual meeting of the American Urogynecologic Society.