[en] PURPOSE:
We assessed the efficacy, safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity.
MATERIALS AND METHODS:
In this 52-week, international, multicenter, double-blind, randomized, placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence (14 or more episodes per week) resulting from multiple sclerosis (227) and spinal cord injury (189) were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo. The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6. Maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points. Adverse events were monitored.
RESULTS:
OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week, respectively, vs 9 episodes per week in 149 on placebo (each dose p<0.001). Also, maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group (each dose p<0.001). Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo (256 and 254 days, respectively, vs 92). The most common adverse events were urinary tract infection and urinary retention. Of patients who did not catheterize at baseline 10% on placebo, 35% on 200 U and 42% on 300 U initiated catheterization due to urinary retention.
CONCLUSIONS:
OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo. Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion. No clinically relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose.
Disciplines :
Urology & nephrology
Author, co-author :
Ginsberg, David
Gousse, Angelo
KEPPENNE, Véronique ; Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Service d'urologie
Language :
English
Title :
Phase 3 efficacy and tolerability study of OnabotulinumtoxinA for Urinary incontinence from neurogenic detrusor overactivity
C.J. Fowler, D. Griffiths, W.C. de Groat The neural control of micturition Nat Rev Neurosci 9 2008 453
M.B. Chancellor, R.U. Anderson, T.B. Boone Pharmacotherapy for neurogenic detrusor overactivity Am J Phys Med Rehabil 85 2006 536
M. Stohrer, B. Blok, D. Castro-Diaz EAU guidelines on neurogenic lower urinary tract dysfunction Eur Urol 56 2009 81
S.J. Foley, J.P. McFarlane, P.J. Shah Vesico-ureteric reflux in adult patients with spinal injury Br J Urol 79 1997 888
W. Hollingworth, J.D. Campbell, J. Kowalski Exploring the impact of changes in neurogenic urinary incontinence frequency and condition-specific quality of life on preference-based outcomes Qual Life Res 19 2010 323
B. Schurch, P. Denys, C.M. Kozma Botulinum toxin A improves the quality of life of patients with neurogenic urinary incontinence Eur Urol 52 2007 850
B. Schurch, P. Denys, C.M. Kozma Reliability and validity of the Incontinence Quality of Life questionnaire in patients with neurogenic urinary incontinence Arch Phys Med Rehabil 88 2007 646
K. Jundt, K. Schreyer, K. Friese Anticholinergic therapy: do the patients take the pills prescribed? Arch Gynecol Obstet 284 2011 663
R. DasGupta, C.J. Fowler Bladder, bowel and sexual dysfunction in multiple sclerosis: management strategies Drugs 63 2003 153
B.T. Benevento, M.L. Sipski Neurogenic bladder, neurogenic bowel, and sexual dysfunction in people with spinal cord injury Phys Ther 82 2002 601
B. Schurch, M. Stohrer, G. Kramer Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results J Urol 164 2000 692
B. Schurch, M. de Seze, P. Denys Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study J Urol 174 2005 196
D.L. Patrick, M.L. Martin, D.M. Bushnell Quality of life of women with urinary incontinence: further development of the incontinence quality of life instrument (I-QOL) Urology 53 1999 71
C.L. Hatheway, C. Dang Immunogenicity of the neurotoxins of Clostridium botulinum J. Jankovic, M. Hallett, Therapy with Botulinum Toxin 1994 Marcel Dekker New York 93 107
G. Karsenty, P. Denys, G. Amarenco Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/ neurogenic overactive bladder: a systematic literature review Eur Urol 53 2008 275
F. Cruz, S. Herschorn, J. Heesakkers Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomized, double-blind, placebo-controlled trial Eur Urol 60 2011 742
K.P. Johnson, B.R. Brooks, J.A. Cohen Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial Copolymer 1 Multiple Sclerosis Study Group Neurology 45 1995 1268
M.S. Freedman Long-term follow-up of clinical trials of multiple sclerosis therapies Neurology 76 2011 S26
A. Manack, S.P. Motsko, C. Haag-Molkenteller Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database Neurourol Urodyn 30 2011 395