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International Urogynecology Journal

, Volume 30, Issue 2, pp 239–244 | Cite as

Do patient characteristics predict which patients with overactive bladder benefit from a higher fesoterodine dose?

  • Howard B. GoldmanEmail author
  • Matthias Oelke
  • Steven A. Kaplan
  • Tekeya Kitta
  • David Russell
  • Martin Carlsson
  • Daniel Arumi
  • Erin Mangan
  • Fady Ntanios
Original Article
  • 130 Downloads

Abstract

Introduction and hypothesis

We sought to determine whether baseline characteristics predict which overactive bladder (OAB) patients benefit from fesoterodine 8 mg versus 4 mg.

Methods

In double-blind, placebo-controlled, flexible-dose trials, baseline characteristics of OAB patients with ≥ 1 urgency urinary incontinence (UUI) episodes/24 h who escalated from fesoterodine 4 mg to 8 mg were evaluated. Possible dose-escalation predictors (age; sex; previous antimuscarinic use; UUI, micturitions, and urgency episodes/24 h; race; body mass index; time to dose escalation; OAB duration) were compared in escalators versus non-escalators. Patients from fixed-dose trials with dose-escalator characteristics were identified (matched dose-escalator sample) to assess changes from baseline with fesoterodine 4 mg, 8 mg, and placebo.

Results

In flexible-dose trials, significant predictors of fesoterodine dose escalation were younger age (≤ 65.8 years), greater number of baseline micturitions (≥ 13.1) and urgency episodes/24 h (≥ 10.9), greater OAB duration (≥ 9.1 years), and more frequent previous antimuscarinic use (58.3%), but not baseline UUI episodes/24 h. In the matched dose-escalator sample (fesoterodine 4 mg: n = 215; 8 mg: n = 198; placebo: n = 217), change from baseline in UUI episodes significantly improved with fesoterodine 8 mg versus 4 mg (P = 0.043) and with both doses versus placebo (P < 0.001). Dry mouth and constipation rates were higher with fesoterodine 8 mg.

Conclusions

Dose-escalator patients had a significantly greater UUI response with fesoterodine 8 mg versus 4 mg. Given the potential for adverse events, fesoterodine 4 mg is recommended to start; however, patients with UUI and identified predictors may benefit from initial treatment with fesoterodine 8 mg or rapid dose escalation.

Keywords

Urinary bladder, overactive Urinary incontinence, urge Fesoterodine Dose-response relationship, drug Randomized-controlled trials 

Notes

Acknowledgements

This study was sponsored by Pfizer Inc., and Pfizer employees participated in the analysis plan, data analysis, and manuscript preparation. Medical writing assistance was provided by Patricia B. Leinen, PhD, of Complete Healthcare Communications, LLC, a CHC Group company, and was funded by Pfizer Inc.

Compliance with ethical standards

Conflicts of interest

H. Goldman is a consultant for Pfizer, Allergan, Medtronic, and Axonics and was previously a consultant for Astellas. M. Oelke is a consultant for and/or has received honoraria or travel expenses from Apogepha, Astellas, Duchesnay, and Pfizer. S. Kaplan is a consultant for Pfizer. T. Kitta has no disclosures. E. Mangan is a former employee of Pfizer Inc. D. Russell, D. Arumi, M. Carlsson, and F. Ntanios are employees of Pfizer Inc.

Summary statement

This study was sponsored by Pfizer Inc., and Pfizer employees participated in the analysis plan, data analysis, and manuscript preparation.

References

  1. 1.
    Coyne KS, Sexton CC, Vats V, Thompson C, Kopp ZS, Milsom I. National community prevalence of overactive bladder in the United States stratified by sex and age. Urology. 2011;77:1081–7.CrossRefGoogle Scholar
  2. 2.
    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.CrossRefGoogle Scholar
  3. 3.
    Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327–36.Google Scholar
  4. 4.
    Coyne KS, Payne C, Bhattacharyya SK, Revicki DA, Thompson C, Corey R, 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.CrossRefGoogle Scholar
  5. 5.
    Andersson KE, Chapple CR, Cardozo L, Cruz F, Hashim H, Michel MC, et al. Pharmacological treatment of overactive bladder: report from the international consultation on incontinence. Curr Opin Urol. 2009;19:380–94.CrossRefGoogle Scholar
  6. 6.
    Chapple CR, Rosenberg MT, Brenes FJ. Listening to the patient: a flexible approach to the use of antimuscarinic agents in overactive bladder syndrome. BJU Int. 2009;104:960–7.CrossRefGoogle Scholar
  7. 7.
    Kelleher C. New agents to treat lower urinary tract and pelvic floor disorders. Can Urol Assoc J. 2013;7:S174–6.CrossRefGoogle Scholar
  8. 8.
    Chapple C, Schneider T, Haab F, Sun F, Whelan L, Scholfield D, et al. Superiority of fesoterodine 8 mg vs 4 mg in reducing urgency urinary incontinence episodes in patients with overactive bladder: results of the randomised, double-blind, placebo-controlled EIGHT trial. BJU Int. 2014;114:418–26.Google Scholar
  9. 9.
    Dmochowski RR, Peters KM, Morrow JD, Guan Z, Gong J, Sun F, et al. Randomized, double-blind, placebo-controlled trial of flexible-dose fesoterodine in subjects with overactive bladder. Urology. 2010;75:62–8.CrossRefGoogle Scholar
  10. 10.
    Weiss JP, Jumadilova Z, Johnson TM 2nd, Fitzgerald MP, Carlsson M, Martire DL, et al. Efficacy and safety of flexible dose fesoterodine in men and women with overactive bladder symptoms including nocturnal urinary urgency. J Urol. 2013;189:1396–401.CrossRefGoogle Scholar
  11. 11.
    Wagg A, Khullar V, Marschall-Kehrel D, Michel MC, Oelke M, Darekar A, et al. Flexible-dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double-blind, placebo-controlled study of fesoterodine in an aging population trial. J Am Geriatr Soc. 2013;61:185–93.CrossRefGoogle Scholar
  12. 12.
    Dubeau CE, Kraus SR, Griebling TL, Newman DK, Wyman JF, Johnson TM 2nd, et al. Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence: a double-blind, placebo controlled trial. J Urol. 2014;191:395–404.CrossRefGoogle Scholar
  13. 13.
    Wyndaele JJ, Schneider T, MacDiarmid S, Scholfield D, Arumi D. Flexible dosing with fesoterodine 4 and 8 mg: a systematic review of data from clinical trials. Int J Clin Pract. 2014;68:830–40.CrossRefGoogle Scholar
  14. 14.
    Staskin D, Khullar V, Michel MC, Morrow JD, Sun F, Guan Z, et al. Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder. Neurourol Urodyn. 2011;30:1480–5.CrossRefGoogle Scholar
  15. 15.
    Cardozo L, Hall T, Ryan J, Ebel Bitoun C, Kausar I, Darekar A, et al. Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation. Int Urogynecol J. 2012;23:1581–90.CrossRefGoogle Scholar
  16. 16.
    Cardozo L, Khullar V, Wang JT, Guan Z, Sand PK. Fesoterodine in patients with overactive bladder syndrome: can the severity of baseline urgency urinary incontinence predict dosing requirement? BJU Int. 2010;106:816–21.CrossRefGoogle Scholar
  17. 17.
    Chapple C, Van Kerrebroeck P, Tubaro A, Haag-Molkenteller C, Forst HT, Massow U, et al. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder. Eur Urol. 2007;52:1204–12.  https://doi.org/10.1016/j.eururo.2007.07.009.CrossRefGoogle Scholar
  18. 18.
    Nitti VW, Dmochowski R, Sand PK, Forst HT, Haag-Molkenteller C, Massow U, et al. Efficacy, safety and tolerability of fesoterodine for overactive bladder syndrome. J Urol. 2007;178:2488–94.CrossRefGoogle Scholar
  19. 19.
    Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.  https://doi.org/10.1093/biomet/70.1.41.CrossRefGoogle Scholar
  20. 20.
    Khullar V, Rovner ES, Dmochowski R, Nitti V, Wang J, Guan Z. Fesoterodine dose response in subjects with overactive bladder syndrome. Urology. 2008;71:839–43.CrossRefGoogle Scholar
  21. 21.
    Cardozo L, Khullar V, El-Tahtawy A, Guan Z, Malhotra B, Staskin D. Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder. BMC Urol. 2010;10:14.CrossRefGoogle Scholar

Copyright information

© The International Urogynecological Association 2018

Authors and Affiliations

  • Howard B. Goldman
    • 1
    Email author
  • Matthias Oelke
    • 2
  • Steven A. Kaplan
    • 3
  • Tekeya Kitta
    • 4
  • David Russell
    • 5
  • Martin Carlsson
    • 5
  • Daniel Arumi
    • 6
  • Erin Mangan
    • 5
  • Fady Ntanios
    • 5
  1. 1.Cleveland Clinic Main CampusClevelandUSA
  2. 2.St. Antonius HospitalGronauGermany
  3. 3.Weill Cornell Medical CollegeNew YorkUSA
  4. 4.Hokkaido UniversitySapporoJapan
  5. 5.Pfizer IncNew YorkUSA
  6. 6.Pfizer EuropeMadridSpain

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