SAN ANTONIO, May 24 /PRNewswire/ -- Results from a Phase II clinical trial evaluating botulinum toxin type A as a treatment for urinary incontinence in patients with the neurogenic form of overactive bladder (OAB) show that botulinum toxin type A produces a rapid and sustained reduction in the number of daily incontinence episodes patients experience, and markedly improves patients' quality of life. These findings were presented today at the 2005 American Urological Association (AUA) annual meeting in San Antonio, Texas by Brigitte Schurch, M.D., Head of the Department of Neurology at the Spinal Cord Injury Centre, University Hospital Balgrist, in Zurich, Switzerland, a lead investigator of the study.
"This is the first placebo-controlled study to investigate botulinum toxin type A injection as a treatment for patients with neurogenic OAB and urinary incontinence," said Prof. Dr. Med. Schurch. "While further study is needed, our results support and enlarge upon previous open-label and other uncontrolled studies suggesting that botulinum toxin may be a promising treatment for this and other urologic conditions."
OAB is the most common cause of urinary incontinence (loss of bladder control) in adults and is estimated to affect between 13-33 million people in the U.S. alone.(1) OAB with urinary incontinence ("wet" OAB) affects approximately 12 million Americans.(2)
Neurogenic OAB (i.e., secondary to another neurologic condition or injury) affects a smaller proportion of the "wet" OAB population in the U.S; however, this condition affects 50 percent of patients with multiple sclerosis, 40 percent of acute stroke patients, 10 to 15 percent of patients 1-year post-stroke,(3) and is commonly associated with patients suffering from complete spinal cord injury. For many patients, urinary incontinence associated with OAB can cause severe medical and psychosocial disability.
"There is an urgent need for new alternatives to currently available treatments. Oral anticholinergic medications are used to treat OAB, but many patients stop taking them due to insufficient efficacy or intolerable side effects such as dry mouth, constipation, blurred vision and drowsiness," explained Dr. Schurch. "Local injection of botulinum toxin type A to block nerve impulses that trigger overactive bladder contractions is a novel approach to the management of neurogenic urinary incontinence, and it may offer potential safety and efficacy advantages for patients with inadequate response to first-line therapy and who do not want to consider invasive surgery."
Risks of Inadequate Management
Left untreated, neurogenic OAB with UI not only has a severe impact on patients' quality of life, but can have serious medical consequences as well -- in particular, by increasing the risk of urinary tract infections (UTIs).(4) In addition, the risk of damaging the upper urinary tract also increases,(5) both because UTIs can spread to the kidneys and because persistently raised detrusor pressure (a characteristic of neurogenic OAB) can lead to a condition called "reflux nephropathy" -- damage resulting from the backward flow of urine into the kidney -- which in severe cases is a significant cause of end-stage chronic renal failure.(6)
About the Study
This was a Phase II, double-blind, randomized, placebo-controlled, parallel-group study conducted over a 26-week period at eight treatment centers in Belgium, France and Switzerland. A total of 59 patients -- men and women 18 years of age and older with neurogenic OAB and incontinence secondary to spinal cord injury (53) or multiple sclerosis (6) -- were randomized in a 1:1:1 ratio to a single treatment of either botulinum toxin type A (200 U), botulinum toxin type A (300 U), or placebo. Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary over 24 weeks. Key urodynamic assessments (maximum cystometric capacity, reflex detrusor volume and maximum detrusor pressure during bladder contraction) were used to provide objective measures of treatment effect on bladder function. Impact of treatment on quality of life was assessed using the Incontinence Quality of Life (I-QoL) questionnaire.
Results of the study show that treatment with botulinum toxin type A injection produced:
* A rapid (within two weeks) and sustained reduction compared to baseline
in the number of daily episodes of urinary incontinence in both
botulinum toxin type A treatment groups, but not in the placebo group.
Mean reductions in daily episodes of urinary incontinence ranged from
32-54% and 42-58% in the 200 U and 300 U groups, respectively. Effects
were apparent by the first 2-week assessment and were maintained
throughout the 24-week study period. Twenty-nine patients experienced
at least one week with no incontinence episodes at all; 83% of these
patients were in the two botulinum toxin type A treatment groups.
* Dramatic improvements in key urodynamic parameters (i.e., bladder
functioning), including: significant increases (p is less than or equal
to 0.05) in mean maximum cystometric capacity (MCC) values (i.e.,
increased ability of the bladder to hold and retain urine); and
significant decreases (p is less than or equal to 0.05) in maximum
detrusor pressure during bladder contraction (MDP) values. Reducing
detruser pressure lowers the risk of vesicoureteric reflux, potentially
preventing upper urinary tract deterioration and possible kidney
damage.(7)
* Marked improvement in I-QoL scores (e.g., avoidance and limiting
behavior, psychosocial impacts and social embarrassment) in botulinum
toxin type A-treated patients throughout the study period compared to
placebo (p is less than or equal to 0.002), reflecting the positive
effects of botulinum toxin type A on urinary incontinence signs and
symptoms. Increases in total I-QoL scores ranged from 18 to 28.3 (a 38-
60% increase from baseline) and 24.6 to 32.7 (a 58-77% increase from
baseline) in the botulinum toxin type A 200 U and 300 U treatment
groups, respectively.
Botulinum toxin type A was safe and well-tolerated in this patient population. There were no drug-related adverse events reported specific to botulinum toxin type A only and no injected patient withdrew from the study due to an adverse event. The only adverse events that occurred in more than one patient per treatment group were urinary tract infection (UTI) and injection site pain. UTIs were reported by 4 (21%), 6 (31.6%) and 3 (14.3%) patients in the botulinum toxin type A (300 U and 200 U) and placebo groups, respectively (rates similar to those reported in patients undergoing urodynamic or clean intermittent self-catheterisation procedures). Injection site pain (reported to be <1 hour duration) was reported by 2 (10.4%) and 1 (4.8%) patients in the botulinum toxin type A and placebo groups, respectively.
This study was funded by Allergan, Inc. (1) The Public Health Implications of Urogenital Disease. Clinician 2003;21(4). Office of Women's Health, U.S. Department of Health and Human Services. (2) The Public Health Implications of Urogenital Disease. Clinician 2003;21(4). Office of Women's Health, U.S. Department of Health and Human Services. (3) Patel M, Coshall C, Rudd AG, et al. Natural history and effects on 2-year outcomes of urinary incontinence after stroke. Stroke. 2001;32:122-127. (4) Wagner TH, Hu TW, et al. Health-related consequences of overactive bladder. Am J Manag Care. 2002;8(19 Suppl):S598-607. (5) Incontinence, 3rd International Consultation, Monaco, June 26-29, 2005. http://www.congress-urology.org/publishing/page.accueil.pub.html (6) Bailey RR. End-state reflux nephropathy. Nephron. 1981;27(6):302-6. (7) Foley SJ, McFarlane JP, Shah PJ. Vesico-ureteric reflux in adult patients with spinal injury. Br J. Urol. 1997;79(6):888-891.
University Hospital Balgrist Zurich, SwitzerlandCONTACT: Brigitte Schurch, M.D., University Hospital Balgrist, Zurich,Switzerland, Tel: 0114113863845