Neil Osterweil

May 20, 2014

ORLANDO, Florida — Botulinum toxin type A (Botox, Allergan), famed for its wrinkle-erasing properties, can also ease the strains of overactive or neurogenic bladder disorders, according to 2 new studies.

"Reconstructive surgeries are still necessary for some patients, but there has been increasing use of botulinum toxin since its approval for neurogenic detrusor overactivity, with minimal associated complications," said Priya Padmanabhan, MD, MPH, assistant professor of urology at the University of Kansas Medical Center in Kansas City.

She presented results from a retrospective study here at the American Urological Association (AUA) 2014 Annual Scientific Meeting.

Dr. Padmanabhan and her colleagues examined changes in the surgical management of neurogenic detrusor overactivity before and after the US Food and Drug Administration approved botulinum toxin A for this indication in August 2011.

It is estimated that 35 million to 42 million adults in the United States have neurogenic bladders, which is associated with an annual economic burden of approximately $65.9 billion, Dr. Padmanabhan reported.

Pharmacologic responses to treatment hover around 70%, and many patients are noncompliant or discontinue drug therapy.

Patients not responsive to medical therapy have traditionally been managed with augmentation cystoplasty, but this procedure is associated with a significant increase in the risk for various complications, including pyelonephritis, bladder stones, small bowel obstruction, chronic kidney disease, and bladder rupture, said Dr. Padmanabhan.

In their chart review, the researchers identified patients diagnosed with neurogenic detrusor overactivity from 2003 to 2013 who were refractory to anticholinergic agents. They compared complication rates in patients who were treated with augmentation cystoplasty, cystectomy, or botulinum toxin A.

Table. Complication Rates

Treatment Group Median Follow-Up (Months) Complication Rate (%)
Cystoplasty 18 37.9
Cystectomy 20 33.3
Botulinum toxin A 9 6.1


Clavien-Dindo surgical complications of grade 3 or greater were seen with cystoplasty and cystectomy (27.6% vs 22.2%), as were ileus (6.9% vs 11.1%) and anastomotic/limb stricture (6.9% vs 11.1%). Bowel obstruction and bladder perforation were seen only with cystoplasty (6.9%).

In contrast, botulinum toxin A injection into the bladder detrusor was associated only with urinary retention (6.1%). No patients treated with either surgical group reported urinary retention.

Dr. Padmanabhan pointed out that at least 2 cost analyses have shown that botulinum toxin injections are 15% to 42% cheaper than surgery.

Her team calculated that using contemporary treatment criteria, 61% of the patients in their cohort who were treated with an invasive reconstructive procedure would be candidates for botulinum toxin A injections.

Liposomal Formulation

In a separate study presented at the meeting, a liposomal formulation of botulinum toxin A was shown to improve symptoms of overactive bladder.

Results were presented by investigator Michael Chancellor, MD, chief medical officer of Lipella Pharmaceuticals in Pittsburgh.

The liposomal formulation, which Dr. Chancellor developed, forms an even protective coating on the lipophilic urothelium, and distributes the botulinum toxin evenly over the surface.

The cohort consisted of 29 men and 33 women with symptomatic overactive bladder who had taken antimuscarinic agents for at least 4 weeks without effect or had experienced intolerable adverse effects.

Patients were randomly assigned to receive either liposomal botulinum toxin or placebo in a 1-time bladder instillation.

Four weeks after instillation, the decrease in the number of micturition events per day was significantly greater in the liposomal group than in the placebo group (–4.64 vs –0.19; = .0252).

The decrease in urgency severity score was also significantly greater in the liposomal group than in the placebo group (= .0181).

Because only a handful of patients had urge incontinence at baseline, the effect of the drug on urge incontinence could not be determined, Dr. Chancellor reported.

The first lines of therapy for neurogenic or overactive bladder are muscarinic receptor antagonists, despite their "modest efficacy, poor long-term persistence, and side effects in some individuals," said Roger Dmochowski, MD, vice chair for surgical quality, safety, and professionalism in the Department of Urology at Vanderbilt University in Nashville, Tennessee.

According to AUA guidelines, behavioral therapy and drugs are the first 2 steps. "I regard them as being essentially the first step," he said.

"The next step is obviously for individuals who either can't tolerate [muscarinic receptor antagonists] or have not achieved the efficacy they want with them," he explained. "Neurotoxins fit very nicely there."

Dr. Dmochowski moderated the briefing during which both studies were discussed, but was not involved in either one.

The study by Dr. Padmanabhan's team was internally supported. Dr. Padmanabhan has disclosed no relevant financial relationships. The study by Dr. Chancellor's team was supported by Lipella Pharmaceuticals. Dr. Chancellor is a board member, officer, and trustee of Lipella Pharmaceuticals, and has financial relationships with Allergan, Novartis, Pfizer, and Watson.

American Urological Association (AUA) 2014 Annual Scientific Meeting: Abstract MP80-14 (Padmanabhan), presented May 20, 2014; abstract MP33-02 (Chancellor), presented May 18, 2014.


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