Urology Times Innovation Celebration: Expert Insights - Episode 7

How onabotulinumtoxinA “revolutionized” treatment of urologic conditions

SAP Partner | <b>Vanderbilt University Medical Center</b>

Urology Times® is celebrating its 50th anniversary in 2022. To mark the occasion, we are highlighting 50 of the top innovations and developments that have transformed the field of urology over the past 50 years. In this installment, Melissa R. Kaufman, MD, PhD, FACS, discusses the significance of onabotulinumtoxinA treatment in patients with overactive bladder. Dr. Kaufman is a Professor of urology, Patricia and Rodes Hart Endowed Chair of Urologic Surgery, and Chief of Reconstructive Urology and Pelvic Health at Vanderbilt University Medical Center, Nashville, Tennessee.

Could you provide a brief overview of the development and emergence of botulinum toxin A and the treatment of overactive bladder?

I really appreciate the opportunity to provide that perspective, because we too often forget the history of these amazing innovations that we commonly employ in urology. There have been few therapies that have so galvanized management of a urologic condition as what we've witnessed over the past decade regarding the use of onabotulinumtoxinA for bladder dysfunction. The range of clinical applications in the urologic realm coupled with a relative ease of administration has revolutionized therapeutic options for several prevalent conditions. There's an entire generation of urologists who trained in the Botox era, who don't recall what it was like to not have it as part of our armentatarium for treatment of medication-refractory overactive bladder.

But the story really begins in the early 1800s. There was a German physician named Justinus Kerner, who noted the presence of a substance in spoiled sausage that killed several dozen people. This “sausage poison” was eventually termed botulism, because the Latin word for sausage is botulus. The organism responsible for botulism, Clostridium botulinum, was eventually isolated in 1895 by Professor Émile Pierre-Marie van Ermengem. [Then] there were pioneering efforts by the ophthalmologist Alan Scott [, MD], [and] botulinum toxin was first approved for medical use in 1989 for strabismus. Shortly thereafter, there were some bold urologists who began investigating how this really powerful neurotoxin can modulate and treat lower urinary tract dysfunction. There was work done by Dennis Dykstra [, MD, PhD], and Brigitte Schurch [, MD], for management of detrusor sphincter dyssynergia. Then Mike Chancellor [, MD], and Christopher Smith [, MD, MBA, MSS], led our discipline from both the basic science and clinical trial perspective in the development of intravesical applications, first with neurogenic patients, but ultimately for treatment of overactive bladder.

When did Botox begin to be widely used by urologist to treat OAB?

It was really only in 2011 that the FDA approved Botox for use in neurogenic detrusor overactivity. There was a landmark clinical trial and manuscript by Victor Nitti [, MD] in 2013,1 that demonstrated efficacy for Botox in patients with idiopathic overactive bladder. Interestingly, in 2013, James Rothman [, PhD], at Yale was awarded the Nobel Prize in Physiology and Medicine for his research defining the mechanism of action of botulinum toxin. However, it wasn't until the 2015 OAB guidelines that were published by the American Urological Association in conjunction with the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction, that Botox [was really integrated] into the treatment algorithm for most urologists.

How would you say that Botox has improved the treatment of patients with OAB?

It's amazing that one of the most lethal toxins known has transformed modern urology and literally millions of patient lives. The symptoms of overactive bladder can progress from being a nuisance to being completely debilitating. Many patients are very reticent to seek treatment as it's an intimate and delicate topic. Having the option of botulinum toxin has really opened the conversation for many patients to provide an accessible option that they're already familiar with, and can really substantially change their quality of life. The ease of administration in the clinic without general anesthesia, along with a real, but limited, side effect profile and substantial efficacy have really shifted the dynamic of treatment of OAB patients. Several manuscripts have demonstrated long-term efficacy and patient satisfaction following Botox treatment with an average response of over 7 months, [with] the most common adverse event actually being urinary tract infection. There is a modest rate of de novo catheterization, which is really part of a shared decision-making process with the patient, but overall, these events are generally transitory.

What qualities make Botox such an innovative treatment for OAB?

In addition to the neuromuscular transmission by blocking release of acetylcholine at the nerve terminal, which suppresses these abnormal contractions that provoke these overactive bladder symptoms, there's increasing evidence for many other mechanisms. Botox has demonstrated the ability to modulate an assortment of neurotransmitters including ATP, substance P, as well as down regulate the purinergic and capsaicin receptors in the sensory apparatus of the bladder, so really, there's innovative treatment forbladder pain, pelvic floor dysfunction as well as prostate disorders, and really further expanding the role of botulinum toxin indications for the future of urology.

Reference

1. Nitti VW, Dmochowski R, Herschorn S, et al. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189(6):2186-2193. doi:10.1016/j.juro.2012.12.022