OnabotulinumtoxinA 100U provides significant improvements in overactive bladder symptoms in patients with urinary incontinence regardless of the number of anticholinergic therapies used or reason for inadequate management of overactive bladder
K-D Sievert, C Chapple, S Herschorn, M Joshi, J Zhou, C Nardo, V W Nitti, K-D Sievert, C Chapple, S Herschorn, M Joshi, J Zhou, C Nardo, V W Nitti
Abstract
Introduction: A prespecified pooled analysis of two placebo-controlled, phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder (OAB) patients with urinary incontinence (UI).
Methods: Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo, sparing the trigone. Change from baseline at week 12 in UI episodes/day, proportion of patients reporting a positive response ('greatly improved' or 'improved') on the treatment benefit scale (TBS), micturition and urgency were evaluated by number of prior anticholinergics (1, 2 or ≥ 3) and reason for their discontinuation (insufficient efficacy or side effects). Adverse events (AE) were assessed.
Results: Patients had taken an average of 2.4 anticholinergics before study enrolment. OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo, regardless of the number of prior anticholinergics (-2.82 vs. -1.52 for one prior anticholinergic; -2.58 vs. -0.58 for two prior anticholinergics; and -2.92 vs. -0.73 for three or more prior anticholinergics; all p < 0.001). The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo (69.0% vs. 37.2% for one prior anticholinergic; 58.8% vs. 24.8% for two prior anticholinergics and 56.4% vs. 22.5% for three or more prior anticholinergics; all p < 0.001). Similar results were observed regardless of the reason for discontinuation. OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups. AEs were well tolerated, with a comparable incidence in all groups.
Conclusion: In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics, onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB. ClinicalTrials.gov: NCT00910845, NCT00910520.
© 2014 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.
Figures
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![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4282287/bin/ijcp0068-1246-f2.jpg)
Figure 3
Change from baseline in daily…
Figure 3
Change from baseline in daily average episodes of (A) urgency and (B) micturition…
Figure 4
Duration of CIC in the…
Figure 4
Duration of CIC in the pooled safety population. CIC was initiated when PVR…
- OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial.Chapple C, Sievert KD, MacDiarmid S, Khullar V, Radziszewski P, Nardo C, Thompson C, Zhou J, Haag-Molkenteller C. Chapple C, et al. Eur Urol. 2013 Aug;64(2):249-56. doi: 10.1016/j.eururo.2013.04.001. Epub 2013 Apr 10. Eur Urol. 2013. PMID: 23608668 Clinical Trial.
- OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial.Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, Yan X, Haag-Molkenteller C; EMBARK Study Group. Nitti VW, et al. J Urol. 2017 Feb;197(2S):S216-S223. doi: 10.1016/j.juro.2016.10.109. Epub 2016 Dec 22. J Urol. 2017. PMID: 28012773 Clinical Trial.
- OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial.Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, Yan X, Haag-Molkenteller C; EMBARK Study Group. Nitti VW, et al. J Urol. 2013 Jun;189(6):2186-93. doi: 10.1016/j.juro.2012.12.022. Epub 2012 Dec 14. J Urol. 2013. PMID: 23246476 Clinical Trial.
- Comparative assessment of the efficacy of onabotulinumtoxinA and oral therapies (anticholinergics and mirabegron) for overactive bladder: a systematic review and network meta-analysis.Drake MJ, Nitti VW, Ginsberg DA, Brucker BM, Hepp Z, McCool R, Glanville JM, Fleetwood K, James D, Chapple CR. Drake MJ, et al. BJU Int. 2017 Nov;120(5):611-622. doi: 10.1111/bju.13945. Epub 2017 Aug 2. BJU Int. 2017. PMID: 28670786 Review.
- [Efficacy and safety of available therapies in the management of idiopathic overactive bladder: A systematic review of the literature].Moyson J, Legrand F, Vanden Bossche M, Quackels T, Roumeguère T. Moyson J, et al. Prog Urol. 2017 Mar;27(4):203-228. doi: 10.1016/j.purol.2016.12.011. Epub 2017 Feb 20. Prog Urol. 2017. PMID: 28228331 Review. French.
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- Meta-Analysis of Randomized Controlled Trials Using Botulinum Toxin A at Different Dosages for Urinary Incontinence in Patients With Overactive Bladder.Gong QQ, Xu YQ, Xu J, Ding XY, Guo C. Gong QQ, et al. Front Pharmacol. 2020 Jan 15;10:1618. doi: 10.3389/fphar.2019.01618. eCollection 2019. Front Pharmacol. 2020. PMID: 32009968 Free PMC article.
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- Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327–36. - PubMed
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- Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50:1306–14. discussion 14–5. - PubMed
-
- Lawrence JM, Lukacz ES, Nager CW, Hsu JW, Luber KM. Prevalence and co-occurrence of pelvic floor disorders in community-dwelling women. Obstet Gynecol. 2008;111:678–85. - PubMed
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- Abrams P, Artibani W, Cardozo L, Dmochowski R, van Kerrebroeck P, Sand P on behalf of the International Continence Society. Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn. 2009;28:287. - PubMed
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- Chiaffarino F, Parazzini F, Lavezzari M, Giambanco V on behalf of Gruppo Interdisciplinare di Studio Incontinenze Urinaria (GISIU) Impact of urinary incontinence and overactive bladder on quality of life. Eur Urol. 2003;43:535–8. - PubMed
- Clinical Trial
- Research Support, Non-U.S. Gov't
- Botulinum Toxins, Type A / administration & dosage
- Botulinum Toxins, Type A / therapeutic use*
- Cholinergic Antagonists / administration & dosage
- Cholinergic Antagonists / therapeutic use*
- Female
- Humans
- Male
- Quality of Life
- Surveys and Questionnaires
- Treatment Outcome
- Urinary Bladder, Overactive / drug therapy*
- Urinary Incontinence / drug therapy*
- Urodynamics / drug effects
- Cholinergic Antagonists
- Botulinum Toxins, Type A
- ClinicalTrials.gov/NCT00910520
- ClinicalTrials.gov/NCT00910845
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4282287/bin/ijcp0068-1246-f3.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4282287/bin/ijcp0068-1246-f4.jpg)
References
- Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327–36.
- Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50:1306–14. discussion 14–5.
- Lawrence JM, Lukacz ES, Nager CW, Hsu JW, Luber KM. Prevalence and co-occurrence of pelvic floor disorders in community-dwelling women. Obstet Gynecol. 2008;111:678–85.
- Abrams P, Artibani W, Cardozo L, Dmochowski R, van Kerrebroeck P, Sand P on behalf of the International Continence Society. Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn. 2009;28:287.
- Chiaffarino F, Parazzini F, Lavezzari M, Giambanco V on behalf of Gruppo Interdisciplinare di Studio Incontinenze Urinaria (GISIU) Impact of urinary incontinence and overactive bladder on quality of life. Eur Urol. 2003;43:535–8.
- Coyne KS, Sexton CC, Irwin DE, Kopp ZS, Kelleher CJ, Milsom I. The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study. BJU Int. 2008;101:1388–95.
- Coyne KS, Payne C, Bhattacharyya SK, et al. The impact of urinary urgency and frequency on health-related quality of life in overactive bladder: results from a national community survey. Value Health. 2004;7:455–63.
- Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol. 2008;54:543–62.
- Yu YF, Nichol MB, Yu AP, Ahn J. Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the California Medicaid program. Value Health. 2005;8:495–505.
- Shaya FT, Blume S, Gu A, Zyczynski T, Jumadilova Z. Persistence with overactive bladder pharmacotherapy in a Medicaid population. Am J Manag Care. 2005;11(4 Suppl):S121–9.
- Gopal M, Haynes K, Bellamy SL, Arya LA. Discontinuation rates of anticholinergic medications used for the treatment of lower urinary tract symptoms. Obstet Gynecol. 2008;112:1311–8.
- Krhut J, Gärtner M, Petzel M, et al. Persistence with first line anticholinergic medication in treatment-naïve overactive bladder patients. Scand J Urol. 2014;48:79–83.
- Nitti VW, Dmochowski R, Herschorn S, et al. EMBARK Study Group. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189:2186–93.
- Chapple C, Sievert KD, MacDiarmid S, et al. OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013;64:249–56.
- Chapple C, Sievert K-D, MacDiarmid S, et al. Pivotal phase 3 study in overactive bladder (OAB) patients with urinary incontinence confirms onabotulinumtoxinA 100U significantly improves all OAB symptoms and patients’ quality of life. Eur Urol Suppl. 2013;12:e741–2.
- D'Souza AO, Smith MJ, Miller LA, Doyle J, Ariely R. Persistence, adherence, and switch rates among extended-release and immediate-release overactive bladder medications in a regional managed care plan. J Manag Care Pharm. 2008;14:291–301.
- Benner JS, Nichol MB, Rovner ES, et al. Patient-reported reasons for discontinuing overactive bladder medication. BJU Int. 2010;105:1276–82.
- Brøstrom S, Hallas J. Persistence of antimuscarinic drug use. Eur J Clin Pharmacol. 2009;65:309–14.
- Zinner N, Noe L, Rasouliyan L, Marshall T, Seifeldin R. Impact of solifenacin on resource utilization, work productivity and health utility in overactive bladder patients switching from tolterodine ER. Curr Med Res Opin. 2008;24:1583–91.
- Swift SE, Siami P, Forero-Schwanhaeuser S. Diary and patient-reported outcomes in patients with severe overactive bladder switching from tolterodine extended release 4 mg/day to solifenacin treatment: an open-label, flexible-dosing, multicentre study. Clin Drug Investig. 2009;29:305–16.
- Visco AG, Brubaker L, Richter HE, et al. for the Pelvic Floor Disorders Network. Anticholinergic therapy vs. onabotulinumtoxinA for urgency urinary incontinence. N Engl J Med. 2012;367:1803–13.
- Makovey I, Davis T, Guralnick ML, O'Connor RC. Botulinum toxin outcomes for idiopathic overactive bladder stratified by indication: lack of anticholinergic efficacy versus intolerability. Neurourol Urodyn. 2011;30:1538–40.
- Abrams P, Chapple CR, Jünemann KP, Sharpe S. Urinary urgency: a review of its assessment as the key symptom of the overactive bladder syndrome. World J Urol. 2012;30:385–92.
- Hung MJ, Ho ES, Shen PS, Sun MJ, Lin AT, Chen GD. Urgency is the core symptom of female overactive bladder syndrome, as demonstrated by a statistical analysis. J Urol. 2006;176:636–40.
- Milsom I, Kaplan SA, Coyne KS, Sexton CC, Kopp ZS. Effect of bothersome overactive bladder symptoms on health-related quality of life, anxiety, depression, and treatment seeking in the United States: results from EpiLUTS. Urology. 2012;80:90–6.
- Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006;49:644–50.
- Apostolidis A, Popat R, Yiangou Y, et al. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005;174:977–82. discussion 82–3.
- Mukerji G, Yiangou Y, Grogono J, et al. Localization of M2 and M3 muscarinic receptors in human bladder disorders and their clinical correlations. J Urol. 2006;176:367–73.
- Burstein R, Zhang XC, Levy D, Aoki KR, Brin MF. Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications to migraine and other pains. Cephalalgia. 2014 [Epub ahead of print]
- Nitti VW, Sievert K-D, Sussman D, et al. OnabotulinumtoxinA in patients with overactive bladder and urinary incontinence: consistent effect over repeat treatment. J Urol. 2013;189(4 Suppl):e559–60.
Source: PubMed