Objective: We report outcomes from the VERSUS (VESIcare® Efficacy and Research Study US) study in a cohort with severe overactive bladder (OAB), defined as patients with a score ≥5 on the Patient Perception of Bladder Condition (PPBC) scale at baseline (on tolterodine extended release [ER] 4mg/day) who remained severe at post-washout (on no drug).
Methods: VERSUS was a 12-week, open-label, flexible-dosing study assessing the efficacy, tolerability and effects on health-related quality of life (HRQOL) of solifenacin in patients with OAB. The current study is a post hoc analysis of a severely affected subgroup, as self-defined using the PPBC scale. Patients had received tolterodine ER 4mg/day for ≥4 weeks but wished to switch therapy because of a lack of sufficient subjective improvement in urgency. They had to have continued to have three or more urgency episodes/24 hours at baseline (pre-washout, i.e. while taking tolterodine ER 4mg/day). After ≥14 days’ washout, patients received oral solifenacin 5mg/day, with the option of continuing/adjusting the dose to 5 or 10mg/day at weeks 4 and 8. Diary-documented improvements in urgency, urge incontinence, frequency, nocturia and nocturnal voids were compared with pre-washout (on tolterodine) and post-washout (on no drug) diary entries. The PPBC scale and Overactive Bladder Questionnaire (OAB-q) assessed patient-reported outcomes. Tolerability was evaluated based on the nature, frequency and severity of observed or reported adverse events (AEs).
Results: In this severe OAB cohort, the mean number of urgency episodes/24 hours decreased by 3.95 (95% CI −4.81, −3.08; p <0.0001) from pre-washout (7.38) to study end (3.26). All other diary variables were also significantly reduced (p <0.0001). Patients had a mean PPBC score of 5.3 at pre-washout and 3.6 at study end, representing an improvement of 1.7 (95% CI −2.0, −1.5; p <0.0001). Patients also reported significant improvements for all OAB-q scales and domains (p <0.0001). Treatment-emergent AEs were mostly mild/moderate, and resulted in few discontinuations (5/116, 4.3%).
Conclusion: In patients with severe OAB symptoms, solifenacin was effective and well tolerated. Solifenacin improved urgency, incontinence, micturition frequency, nocturia and nocturnal voids in patients continuing to experience urgency episodes on tolterodine ER 4mg/day. Patients experienced improvements in HRQOL and perceived bother from OAB.
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This study was supported by Astellas Pharma US, Inc. and GlaxoSmithKline. Clinical study number: 905-UC-006; trial registry number: NCT00454740.
The authors would like to thank the entire clinical development team, led by Allam Fakhoury, PharmD, for their contributions to the success of this programme. Medical writing and editorial support was provided by Sue Cooper at Envision Pharma.
Dr Swift currently receives or has previously received research grants from Duramed, Pfizer and Astellas, is on the speakers bureau for Pfizer and Astellas, and is on the Advisory Board for Merck, Pfizer and Astellas. Dr Siami is currently or was previously a consultant and speaker for Bard, Astellas, GlaxoSmithKline, Pfizer and Boehringer-Ingelheim, an investigator for Pharmacia, Bayer and GlaxoSmithKline, and on the Advisory Board for Bayer and GlaxoSmithKline. Dr Forero-Schwanhaeuser is an employee of GlaxoSmithKline.
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