Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity, "Beyond the Abstract," by David A. Ginsberg, MD

BERKELEY, CA ( - The primary medical therapy for neurogenic detrusor overactivity (NDO) secondary to neurogenic bladder (NGB) is anticholinergics. Immediate-release oxybutynin first obtained FDA-approval in 1975.

Since then a variety of dosing methods for oxybutynin have been approved (i.e., extended-release, transdermal gel, transdermal patch) as have many other anticholinergic drugs such as tolterodine, solifenacin, darifenacin, trospium chloride, and fesoterodine. Despite these advancements, anticholinergics continue to be a suboptimal therapy for many patients with NGB secondary to suboptimal efficacy, bothersome side effects such as dry mouth or constipation or a combination of the two.

The approval of onabotulinumtoxinA for NDO is truly a huge advance in therapy for our patients with bothersome NDO/NGB who are suboptimally treated with anticholinergics. Trials that led to approval of this drug showed that treatment with 200 U of onabotulinumtoxinA in spinal cord injury (SCI) and multiple sclerosis (MS) patients resulted in significant improvements in both clinical (decreased incontinence, increased volume voided, increased quality of life) and urodynamic (increased maximum cystometric capacity, decreased maximum detrusor pressure) parameters. This therapy is administered cystoscopically and lasts, on average, for approximately 10 months. The most common adverse events include urinary tract infection and urinary retention requiring temporary clean intermittent catheterization (CIC).

The issues related to CIC deserve a bit more discussion. First, it is important to appreciate that the outcome of incomplete emptying/retention leading to CIC is often the goal when treating patients with NGB. Reluctance to institute CIC is rarely an issue with patients with SCI as that is often begun right after their injury and continued after discharge from their initial rehabilitation stay. However, this can be much more of an issue with MS patients, many of whom may be voiding volitionally prior to the administration of onabotulinumtoxinA. This was certainly reflected in our study with 83% of SCI patients regularly performing CIC at baseline compared to 35% of MS patients.

During the trial, 35% of patients initiated CIC after injection with 200 U onabotulinumtoxinA compared to 10% of patients who were treated with placebo. Why would someone on placebo need to start CIC? This is likely due to the fact that some patients who entered the study might have actually clinically benefited from CIC before receiving an injection of either placebo or onabotulinumtoxinA. Therefore, the actual risk of requiring CIC for a temporary period of time after 200 U of onabotulinumtoxinA is the difference between the two numbers - 25%.

However, it is also important to understand how most MS patients are clinically managed. Patients with NDO, not optimally treated with anticholinergics, who are already on CIC at baseline, will clearly benefit from a 200 U dose. Patients who are volitionally voiding prior to onabotulinumtoxinA may benefit from a lower dose. In fact, I inject 100 U to the majority of MS patients who are volitionally voiding that I treat with onabotulinumtoxinA (and do not have an elevated PVR at baseline). The hope is that we are able to provide the patient with an optimal balance - adequate improvement both clinically and urodynamically but not so much that they need to begin CIC. Trials are presently underway to evaluate this clinical scenario.

Finally, I believe it is important that we appreciate both the mental and physical hurdles that need to be cleared when we consider starting a patient on CIC. For some MS patients it is just not possible due to a lack of upper extremity dexterity, sensation, body habitus, etc. Thankfully, this is not an issue for most patients. However, the mental hurdle can be quite challenging. Most patients do no understand what is meant when the urologist tells them they might have to catheterize for a period of time. It is important that we explain that this is not an indwelling catheter but rather a catheter than goes in and out of the bladder several times a day. The patient needs to appreciate that all of their voids may not require CIC; in fact, most of my patients who require CIC post-injection of onabotulinumtoxinA do so no more than 2-3 times/day. In addition, if CIC is required, it is needed for a temporary period of time. In addition, within the trial setting, improvements in quality of life noted after onabotulinumtoxinA injection were not impacted in a negative manner with the institution of CIC. Lastly, a major concern with many patients with MS is that if they begin CIC this is a sign that their disease is progressing. It is important the patients understand that the initiation of CIC does not indicate a worsening of MS and, in fact, if used in conjunction with onabotulinumtoxinA injection, will often lead to significant improvements with their lower urinary tract function.

Written by:
David A. Ginsberg, MD as part of Beyond the Abstract on This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Urology
University of Southern California
Norris Cancer Center
1441 East Lake Ave., Suite 7416
Los Angeles, California USA 90033

Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity - Abstract

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