Do patient characteristics predict which patients with overactive bladder benefit from a higher fesoterodine dose?
- 130 Downloads
Introduction and hypothesis
We sought to determine whether baseline characteristics predict which overactive bladder (OAB) patients benefit from fesoterodine 8 mg versus 4 mg.
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.
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.
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.
KeywordsUrinary bladder, overactive Urinary incontinence, urge Fesoterodine Dose-response relationship, drug Randomized-controlled trials
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.
This study was sponsored by Pfizer Inc., and Pfizer employees participated in the analysis plan, data analysis, and manuscript preparation.
- 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
- 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
- 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