Impact of solifenacin on diary-recorded and patient-reported urgency in patients with severe overactive bladder (OAB) symptoms

Abstract

Objective:

It is widely recognized that patient perception of overactive bladder (OAB) symptoms can vary considerably from mild to severe bother. This post hoc analysis reports outcomes in patients with severe OAB symptoms at baseline taken from the VESIcare Efficacy and Safety in PatieNts with Urgency Study (VENUS).

Methods:

VENUS was a 12-week, randomized, double-blind, placebo-controlled trial of solifenacin (5 or 10 mg/day, flexibly dosed) in OAB patients. The primary endpoint in VENUS was mean change from baseline to study end in urgency episodes/day using 3-day bladder diaries. Secondary endpoints included other diary endpoints (frequency, incontinence, and nocturia), warning time (WT; time between first sensation of urgency to voiding), and patient-reported outcome (PRO) measures of urgency (the Indevus Urgency Severity Scale [IUSS] and Urgency Perception Scale [UPS]) and of symptom bother and health-related quality of life (HRQL) (the Patient Perception of Bladder Condition [PPBC] and Overactive Bladder Questionnaire). For this analysis, severe OAB was defined as baseline PPBC score ≥5 (1 = no problems, 6 = many severe problems). Trial registration: NCT00454896

Results:

In total, 158/707 (22.3%) patients in the full analysis set (FAS) reported severe OAB symptoms. Solifenacin reduced mean urgency episodes/day versus placebo in the severe subgroup (−4.6 vs. −3.1, p = 0.1150), similar to the significant reduction observed in the FAS (−3.9 vs. −2.7, p < 0.0001). Solifenacin also improved the other diary endpoints and PRO measures in the severe subgroup; these changes were consistent with the significant solifenacin- versus placebo-related improvements for the FAS. Treatment-emergent adverse events were mostly mild/moderate, and few patients taking solifenacin or placebo discontinued treatment in the severe subgroup (4.5% vs. 6.5%) or FAS (6.5% vs. 4.6%). Key limitations are that VENUS was not powered to detect treatment differences in subgroups, and that the lack of a standardized definition of OAB symptom severity may limit the generalizability of the findings.

Conclusions:

Patients with severe OAB symptoms showed objective and subjective improvements in symptoms, symptom bother, HRQL, and urgency severity with solifenacin similar to the FAS. Solifenacin was also well-tolerated in this subgroup.

Key words:

• Overactive bladder
• Patient-reported outcomes
• Solifenacin
• Symptom severity
• Urgency

Transparency

Declaration of funding

The VENUS study was supported by Astellas Pharma US Inc. and GlaxoSmithKline.

Declaration of financial/other relationships

S.R.S. and M.R.T., as study investigators, received research support from the VENUS study sponsors, Astellas Pharma US Inc. and GlaxoSmithKline. M.R.T. has been a consultant and a speaker for Astellas Pharma US Inc. S.F.S. is an employee of GlaxoSmithKline. W.H. is an employee of Astellas Pharma Global Development Inc.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewers 1 and 2 have disclosed that they have no relevant financial relationships. Peer Reviewer 3 has disclosed that he/she is the recipient of research/grant funding from Pfizer, Astellas and Allergan; and is a consultant/advisor to Pfizer, Astellas, Allergan, Novartis, Tanabe, Recordati and ONO.

Acknowledgments

Editorial and medical writing assistance was provided by Nick Brown, PhD, a medical writer at Envision Scientific Solutions and was funded by Astellas Pharma Global Development Inc. and GlaxoSmithKline.

Data in this manuscript have been presented in part at the 29th Annual Scientific Meeting of the American Urogynecologic Society, September 4–6, 2008, Chicago, IL, USA; the 60th Annual Meeting of the North Eastern Sectional of the American Urological Society (AUA), September 17–21, 2008, Santa Ana Pueblo, NM, USA; the 39th Annual Conference of the Society of Urologic Nurses and Associates, October 3–6, 2008, Philadelphia, PA, USA; the 38th Annual Meeting of the International Continence Society, October 20–24, 2008, Cairo, Egypt; the 84th Annual Meeting of the Western Sectional of the AUA, October 26–30, 2008, Monterey, CA, USA.