Characteristics of antimuscarinic responders versus suboptimal responders in a randomized clinical trial of patients with overactive bladder symptoms

Abstract

Objective: To assess the characteristics of tolterodine extended-release (ER) 4 mg responders and suboptimal responders (≤50% decrease in UUI episodes/24 h) among patients with overactive bladder (OAB), including urgency urinary incontinence (UUI), and identify predictors of a >50% UUI response with fesoterodine 8 mg in tolterodine suboptimal responders.

Methods: Adult patients with OAB symptoms for ≥6 months and ≥8 micturitions, and ≥2 and <15 UUI episodes/24 h at week −2 received open-label tolterodine ER 4 mg during a 2 week run-in. Suboptimal responders after tolterodine treatment (week 0) were randomized to fesoterodine (4 mg for 1 week, 8 mg for weeks 2–12) or placebo once daily. Post-hoc analyses compared the percentage change from week −2 to week 0 in UUI episodes/24 h in tolterodine responders versus suboptimal responders and identified significant predictors of a UUI response at week 12 with fesoterodine 8 mg among tolterodine suboptimal responders.

Results: Of 897 patients, 610 (68%) were UUI suboptimal responders during the run-in period. UUI episodes/24 h at week −2 were similar in tolterodine responders and suboptimal responders (4.2 vs. 4.3), but responders showed a significantly greater median percentage decrease in UUI episodes/24 h after tolterodine treatment at week 0 (80.0% versus 15.3%; p < .0001). During double-blind treatment, the percentage of patients with a UUI response at week 12 was significantly greater with fesoterodine (69.9%) than placebo (57.0%; p = .0027). Fesoterodine (vs. placebo), no previous antimuscarinic use before tolterodine run-in, and less UUI severity at baseline were significant predictors of a UUI response.

Conclusions: For patients with OAB, including UUI, who were treated initially with tolterodine and showed a suboptimal UUI response, nearly 70% demonstrated a UUI response with second-line fesoterodine 8 mg. No antimuscarinic use before tolterodine and fewer baseline UUI episodes were significant predictors of a UUI response with fesoterodine.

Keywords:

• Overactive bladder
• urgency urinary incontinence
• treatment response
• antimuscarinics
• fesoterodine
• tolterodine

Transparency

Declaration of funding

This study was sponsored by Pfizer Inc.

Author contributions: Pfizer employees participated in the study design, collection and analysis of data, and manuscript preparation.

Declaration of financial/other relationships

S.H. has disclosed that he has relationships with Pfizer, Astellas, Allergan, Merus, and Promedon. S.A.K. has disclosed that he has relationships with Pfizer and Merck. L.C. has disclosed that she has relationships with Allergan, Astellas, BMR, and Pfizer. D.S., D.A., M.C., D.C. and F.N. have disclosed that they are employees of Pfizer Inc. D.C. has disclosed that he holds shares in Pfizer Inc. L.G. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

Medical writing assistance was provided by Patricia B. Leinen PhD of Complete Healthcare Communications LLC and was funded by Pfizer Inc.

Previous presentation: Data from this study was previously presented at the 29th Annual European Association of Urology Congress, Stockholm, Sweden, 4–7 April 2014.