Patient-reported outcomes in patients with overactive bladder treated with mirabegron and tolterodine in a prospective, double-blind, randomized, two-period crossover, multicenter study (PREFER)

Sender Herschorn,Jonathan Fialkov,David Staskin,Carol R Schermer,Terry Walsh,Katherine Gooch,Le Mai Tu

doi:10.1186/s12955-018-0892-0

Abstract

BackgroundThe PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). In this analysis of PREFER, patient-reported outcomes (PROs) were assessed during treatment.MethodsPREFER was a two-period, 8-week crossover, double-blind, phase IV study (NCT02138747) of treatment-naïve adults with OAB ≥3 months randomized to 1 of 4 treatment sequences (M/T; T/M; M/M; T/T), separated by a 2-week washout. Tolterodine ER was dosed at 4 mg for 8 weeks and mirabegron was dosed at 25 mg for 4 weeks then increased to 50 mg for the next 4 weeks. At each visit, PROs related to treatment satisfaction, quality of life and symptom bother were assessed using the OAB Satisfaction (OAB-S; 3 independent scales/5 single-item overall assessments), OAB-q (total health-related QoL [HRQoL] and subscales [Sleep, Social, Coping, Concern] and Symptom Bother scale) and Patient Perception of Bladder Condition (PPBC) questionnaires. Responder rates were reported for OAB-q subscales based on a minimal important difference (MID; ≥ 10-point improvement) and OAB-S Medication Tolerability score ≥ 90.ResultsIn total, 358 randomized patients received ≥1 dose of double-blind study medication and completed ≥1 post-baseline value (OAB-S scale, OAB-q, PPBC): M/T (n = 154), T/M (n = 144), M/M (n = 30) or T/T (n = 30). At end of treatment (EoT), mirabegron and tolterodine ER were associated with similar mean improvements in 7 of the 8 OAB-S scores investigated, OAB-q scales and PPBC. A higher percentage of patients achieved clinically relevant improvements (MID) in OAB-q scales and OAB-S Medication Tolerability score during treatment with mirabegron than tolterodine ER.ConclusionsOn average, patients with OAB experienced improvements in treatment satisfaction, HRQoL and symptom bother that were of a similar magnitude during treatment with mirabegron or tolterodine ER. However, during mirabegron treatment, patients were more likely to achieve clinically relevant improvements in tolerability and HRQoL (as measured by the MID for the OAB-q or an OAB-S Medication Tolerability score ≥ 90) than during tolterodine ER treatment.Trial registrationNCT02138747; registered May 13, 2014.

Highlights

The A Prospective (PREFER) study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB)
The OAB-q is useful for assessing treatment effects on various aspects of quality of life (QoL) such as social interaction, coping, sleep, and the extent of bother associated with symptoms [6, 7], and the single-item Perception of Bladder Condition (PPBC) evaluates patients’ perception of their current bladder problems [8]
Baseline OAB-Treatment Satisfaction (OAB-S), OAB-q scales and PPBC premedication scales were consistent across sequences in period 1 and overall treatment group (Table 1), and were indicative of moderate levels of symptom bother, moderate problems with bladder condition (PPBC > 4), and QoL

Summary

Introduction

The PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). Patients with OAB tend to seek treatment once their QoL is affected, and are more likely to persist with their medication if they perceive meaningful improvements in QoL [5] This underlies the importance of evaluating the benefits of a treatment according to objective changes in bladder parameters (e.g. micturition frequency, incontinence episodes) and via subjective outcomes related to QoL, perception of symptoms, and general wellbeing. The OAB-q is useful for assessing treatment effects on various aspects of QoL such as social interaction, coping, sleep, and the extent of bother associated with symptoms [6, 7], and the single-item PPBC evaluates patients’ perception of their current bladder problems [8]. The OAB-S was developed to measure the ‘multidimensional concept’ of treatment satisfaction over a number of domains, including 5 independent scales (OAB Control Expectations, Impact on Daily Living with OAB, OAB Control, OAB Medication Tolerability, and Satisfaction with OAB Control) and 5 single-item overall assessments (Patient’s Fulfillment of OAB Medication Expectations, Interruption of Day-to-Day Life Due to OAB, Overall Satisfaction with OAB Medication, Willingness to Continue OAB Medication, and Improvement in Day-toDay Life Due to OAB Medication) [9]

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