First-of-Its-Kind Study Shows Botox (Botulinum Toxin Type A) Significantly Improves Idiopathic Detrusor Overactivity (IDO) in Patients With Symptoms of Overactive Bladder

Treatment Benefits Were Maintained for at Least 24 Weeks, According to Report Published in The Journal of Urology

LONDON, May 15, 2007 /PRNewswire/ -- Researchers from Guy's Hospital and King's College London School of Medicine have announced the results from the first randomized, double-blind, placebo-controlled study evaluating botulinum toxin type A (BTX-A, BOTOX(R)) as a treatment for idiopathic detrusor overactivity (IDO) in patients with symptoms of overactive bladder (OAB). The trial results which are published in the June 2007 issue of The Journal of Urology show that BTX-A is safe and effective for this use and that the beneficial effects -- including improved quality of life -- persist for at least 24 weeks.

"The findings of this study are important because there is a need for new treatments for OAB patients who have unsatisfactory responses to therapies which are currently available and who do not want to consider invasive surgery," said Mr. Arun Sahai, who was a principal investigator of the study during his time as a research fellow at Guy's Hospital, London. "This study demonstrated that botulinum toxin type A may be a promising treatment option for patients with OAB symptoms."

OAB is characterized by feelings of urgency to urinate, with or without incontinence, and is usually accompanied by increased urination frequency and nocturia (excessive urination at night). A large proportion of OAB patients have what is referred to as idiopathic detrusor overactivity or IDO -- excessive activity of the muscles that contract the bladder, due to an unknown cause -- and are treated with drugs called anticholinergics (e.g., tolterodine). However, many OAB patients discontinue medication due to insufficient relief of symptoms or intolerable side effects that can include dry mouth, dry eyes, constipation and headache.

"This study showed that this treatment had real benefits for patients for whom previous treatments had not worked," said Mr. Prokar Dasgupta, consultant urologist at Guy's Hospital, honorary senior lecturer at King's College London, and a co-principal investigator of the study. "These were patients who were seriously affected by their OAB symptoms. At basline, 81 percent of patients in the botulinum toxin type A treatment group and 67 percent in the placebo treatment group were experiencing urge urinary incontinence daily."

OAB is more common than osteoarthritis or diabetes(1,2) and is estimated to affect 16-17% of the population in the U.S. and Western Europe.(3) In addition, the economic burden of OAB is substantial. In the U.S., for example, the total economic cost of OAB has been estimated at $12 billion in 2000 (including costs incurred in the community and institutions).

About the Study

The double-blind trial included 34 patients with OAB and confirmed IDO who had failed on a trial of anticholinergic therapy for six weeks or more due to either poor efficacy or tolerability. They were randomly assigned to treatment with BTX-A 200 U (BOTOX(R)) (16 patients) or placebo (18 patients). The primary outcome measure was change in maximum cystometric capacity (MCC), a measure of urinary bladder capacity. Secondary outcome measures included changes in OAB symptoms, other measures related to urinary bladder filling and pressure, symptoms of urgency and incontinence, and quality of life (QoL). Patients were assessed at 4 and 12 weeks post-injection, at which point the study was unblinded; BTX-A patients were further followed until 24 weeks.

BTX-A treatment significantly increased MCC vs. baseline at 4 weeks (by about 72%) and 12 weeks (by about 45%), compared to a 15 percent decrease in placebo patients at both time points. The differences between MCC changes for the BTX-A and placebo groups were significant at both time points (p<0.0001 and p<0.0011, respectively). Likewise, at 4 and 12 weeks compared to baseline, BTX-A also significantly improved all secondary endpoints, including measures of bladder filling and pressure; urination frequency, urgency urinary incontinence episodes, and urgency (at 4 weeks only); and QoL. All these improvements were significantly greater than with placebo vs. baseline.

The extension study lasting until week 24 suggested that most of these beneficial effects of BTX-A were maintained for at least 24 weeks. At baseline, 81% of patients in the BTX-A group were experiencing urgent urinary incontinence daily, but urinary frequency normalized in 57% at 4 weeks, and 36% maintained this benefit at 24 weeks; further, 50% were continent at follow-up, and the improvement lasted 24 weeks. Complete resolution of detrusor overactivity was observed in 44% of BTX-A patients at 4 weeks, though this dropped to 25% by 24 weeks.

Quality of life was assessed using the IIQ-7 and UDI-6 and was significantly better in the BTX-A group compared with placebo at both 4 and 12 weeks post-injections.

Treatment with BTX-A was well tolerated and there were no major complications. Six patients in the BTX-A group had symptomatic post void residual (PVR) at follow-up requiring clean intermittent self catheterization (CISC). Seven patients developed symptomatic urinary tract infection, six of whom were performing CISC. Mr. Sahai's and Mr. Dasgupta's co-researcher was Mohammad S. Khan, FRCS (urol) FEBU, consultant urologist at Guy's Hospital, London. BTX-A is not currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of any form of OAB, nor is it currently approved for this use by regulatory agencies in Europe. This research was funded by Allergan, Inc and through a project grant from the British Urological Foundation.

    (1) National Diabetes Information Clearinghouse, a service of the National

        Institute of Diabetes and Digestive and Kidney Disease (DIDDK), NIH,

        http://diabetes.niddk.nih.gov/dm/pubs/statistics/#7

    (2) National Institute of Arthritis and Musculoskeletal and Skin Disease,

        National Institute of Health (NIH),

        http://www.niams.nih.gov/hi/topics/arthritis/oahandout.htm#1

    (3) Sahai A, Khan M, Fowler CJ, Dasgupta P. Botulinum toxin for the

        treatment of lower urinary tract symptoms: a review. Neurourology and

        Urodynamics 2005;24:2-12

CONTACT: Katie Fleming of Guy's and St Thomas' NHS Foundation Trust, +0207188 5577, Katie.fleming@gstt.nhs.uk

Web site: http://www.guysandstthomas.nhs.uk/

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Posted: May 2007

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