Alicia Ault

May 17, 2015

NEW ORLEANS — OnabotulinumtoxinA (Botox) can be safely used as a chronic therapy for overactive bladder and neurogenic detrusor overactivity, according to the results of two new studies.

These are the first long-term reports on onabotulinumtoxinA for overactive bladder and incontinence, and are likely to give patients "reassurance that if you help them now, they're likely to be good for multiple years in the future," said Michael Chancellor, MD, director of the Aikens Neurourology Research Center at the Beaumont Health System in Royal Oak, Michigan.

The studies were large enough and long enough to help reassure clinicians that onabotulinumtoxinA is long-lasting and that "the side effects, in fact, go down," Dr Chancellor told Medscape Medical News.

Results from both studies were presented here at the American Urological Association 2015 Annual Meeting.

OnabotulinumtoxinA was approved by the US Food and Drug Administration (FDA) in 2013 to reduce urinary incontinence in patients with overactive bladder who don't respond to anticholinergics or can't use them.

In the first study, Victor Nitti, MD, from the NYU Langone Medical Center in New York City, and his colleagues evaluated the use of onabotulinumtoxinA in patients with overactive bladder who experienced urinary incontinence from 2009 to 2014. Patients could seek treatment — onabotulinumtoxinA 100 units delivered with 20 needle pricks into the bladder wall — on an as-needed basis for up to 3 years.

The team recruited 829 patients, but only 429 completed the trial. Most of the patients who dropped out cited personal reasons; only 80 stopped because of lack of efficacy or because of an adverse event, Dr Nitti reported.

These results give us the encouragement that it is something that can be used in the long term.

Twelve weeks after treatment, there was a reduction in urinary incontinence episodes from a baseline of 5.6 per day to 3.1 to 3.8 per day, depending on the number of treatments patients received (range, 1 - 6). Regardless of the number of treatments, 78% to 81% of patients reported "improvement" or "great improvement" on the Treatment Benefit Scale. The median duration of the effect was 7.6 months, but for about one-third of patients, it lasted a year or more.

There was no increase in adverse effects with repeated treatment, and effects that were observed were similar to what had been seen in approval studies, with urinary tract infection being the most common. The catheterization rate was consistent, regardless of the number of treatments.

"We did not see any new safety signals upon retreatment with onabotulinumtoxinA," said Dr Nitti, who estimated that one-third of his overactive bladder patients would be eligible for such therapy, but that probably only 20% of those would choose to receive the treatment.

Although it would be nice to have even longer-term data, he said, these results "give us the encouragement that it is something that can be used in the long term, recognizing that we don't know specifically what happens at year 10, 15, 20."

Neurogenic Detrusor Overactivity

Results from the second study were presented by Eric Rovner, MD, from the Medical University of South Carolina in Charleston.

Dr Rovner's team evaluated the use of onabotulinumtoxinA in "a highly symptomatic population" of patients with neurogenic detrusor overactivity — primarily related to spinal cord injury or multiple sclerosis.

The 4-year study involved 227 patients, but he presented data on the 122 patients who received the 200 unit dose approved by the FDA.

All patients had failed oral drug therapy and experienced an average of 4.3 incontinence episodes per day; 70% were on intermittent catheterization at the start of the trial.

Patients could request treatment as needed.

"The efficacy of the medication does not change over time," Dr Rovner reported. The majority of patients experienced a 50% or greater reduction of incontinence episodes per day in each year of treatment, and almost half had a complete elimination of incontinence.

The median time between treatments was just over 9 months. The most common adverse effect was urinary tract infection. During the first year of the study, the de novo catheterization rate was 39%; that decreased to 0% by the fourth year.

"There were no new safety signals over time," said Dr Rovner.

Higher Real-World Catheterization Rates?

A third study, presented by Olufenwa Milhouse, MD, from Metro Urology in Woodbury, Minnesota, was conducted to see whether that rate of catheterization held-up in real-world practice.

Catheterization is a well-documented adverse effect of onabotulinumtoxinA, and is generally thought to affect 6% to 7% of patients. The mechanism of action of onabotulinumtoxinA can cause urine retention, so patients are counseled on how to self-catheterize.

Dr Milhouse's team retrospectively examined the medical records of 292 patients with idiopathic overactive bladder who were treated with onabotulinumtoxinA from 2010 to 2014. They identified 103 patients who met the study criteria.

Catheterization after treatment was required by 25% of the patients, which is much higher than the reported rate. About one-fifth of the 103 patients developed a urinary tract infection, but in patients who were catheterized, that rose to 62%.

The researchers looked for predictive factors for catheterization, but could not find any that were statistically significant, Dr Milhouse reported.

Three-quarters of the total patient population said that they were satisfied with treatment, and half went on to have subsequent injections.

Some patients "were happy to continue treatment because at least they were dry and not in diapers or pads," said Dr Milhouse. Although "patients cringe at" catheterization, some elected to continue treatments.

Dr Nitti said that in his clinical practice, the rate of catheterization is a bit higher than 6% because he has older patients, but "it's nowhere near 25%."

And Dr Rovner said the rate is closer to 10% in his practice, but he does not administer onabotulinumtoxinA to anyone with idiopathic overactive bladder who is unwilling to catheterize. "If I don't explain that potential outcome or they don't understand it and it happens, it's potentially an unfavorable outcome," he said, which is why it's important to counsel patients.

Dr Chancellor said he agrees. "I say that if you're not willing to potentially catheterize yourself, we're not going to go there," he told Medscape Medical News.

Dr Chancellor reports financial relationships with Allergan, Astellas, Cook Group, Merck, Ono Pharmaceuticals, Pfizer, and Targacept; has an investment interest in Lipella Pharmaceuticals; and is involved in a trial with Medtronic and Pfizer. Dr Nitti reports financial relationships with Allergan, American Medical Systems, Astellas, Coloplast, Pfizer, Pneumoflex, Serenity Pharmaceuticals, Theracoat, and Uroplasty; and has an investment interest in Serenity Pharmaceuticals. Dr Rovner reports financial relationships with Allergan, American Medical Systems, Amphora, Astellas, Ferring, Medtronic, and Taris; is involved in a trial study with Ion Innovations and the National Institute of Diabetes and Digestive and Kidney Disease; and has an investment interest in NextMed. Dr Milhouse has disclosed no relevant financial relationships.

American Urological Association (AUA) 2015 Annual Meeting: Abstracts PI-04; PD1-01; PD27-08, Presented May 15, 2015 at a news conference.


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