With what degree of improvement in Patient Reported Outcome Measures is resolution of OAB symptoms associated? Data from a pooled analysis of OAB treatment with fesoterodine.

Wagg A1, LaBossiere J R2, Herschorn S2, Fernet M3, Carlsson M3, Oelke M4

Research Type

Clinical

Abstract Category

Overactive Bladder

Abstract 96
Open Discussion ePosters
Scientific Open Discussion ePoster Session 7
Wednesday 29th August 2018
12:50 - 12:55 (ePoster Station 3)
Exhibition Hall
Overactive Bladder Quality of Life (QoL) Female Male
1. University of Alberta, Edmonton, Alberta, Canada, 2. University of Toronto, Toronto, Ont, Canada, 3. Pfizer Canada, Montreal, QC, Canada, 4. St. Antonius-Hospital Akademisches Lehrkrankenhaus der WWU Münster, Gronau, Germany
Presenter
M

Matthias Oelke

Links

Poster

Abstract

Hypothesis / aims of study
Overactive bladder (OAB) is a common, debilitating disorder with a negative impact upon health and quality of life outcomes.  Treatment with antimuscarinic agents remains the first line therapeutic option for symptom control, supported by clinical trials.  This study aimed to examine the relationship between disease variable resolution at end of 4, 8 or 12 weeks treatment with fesoterodine and the proportion of patients achieving a significant improvement in Patient Reported Outcome Measures (PROM).  The study also sought to describe the proportion of patients which make a significant improvement in PROM who also achieve either total or 50% resolution in their OAB symptoms.
Study design, materials and methods
This study used pooled data from 6 fixed dose studies of fesoterodine (A0221008, A0221012, A0221013, A0221046, A0221094, A0221095) each a parallel, 12 week, double blind RCT to describe the degree of symptom improvement by end of treatment weeks 4,8 and 12, after exposure to either 4mg, or 8mg of fesoterodine.  Analysis was based on the full analysis set which included all subjects who took at least one dose of assigned study drug and contributed data to at least one baseline and post-baseline efficacy assessment with the baseline value of the outcome variable > 0. The following measures were used: the proportion of patients achieving a 100% and 50% reduction in 
•	Urinary urgency episodes/24h (UUE) 
•	Urinary urgency incontinence (UUI) episodes /24h (where baseline UUI episodes>0)
•	Daytime micturition frequency (DMF) /24 h (100% resolution defined as DMF=8/24h)
•	Nocturnal Micturition Frequency/24h (NMF) (where 100% resolution is defined as N≤1)
•	All 3 symptoms, reduction in all of urgency, DMF and UUI
PROMs included the Patient Perception of Bladder Condition, Overactive Bladder Questionnaire (OAB-q) and The Health-Related Quality of Life (HRQL) subscales of OAB-q (Coping, Concern, Sleep and Social Interaction) .  A significant change in PPBC was defined as a shift of 1 category from baseline. Change in OAB-q symptom bother score was calculated at each time point relative to baseline. The proportion of patients achieving the MID on OAB-q (10 points) was calculated according to the degree of symptom resolution at 4 and 12 weeks relative to baseline.
Results
6689 patients (fesoterodine 4mg, 1373, fesoterodine 8mg 3263, placebo 2053, mean age 58.4y) were included, Table 1 shows the proportion of patients with a 50% or 100% response in OAB symptoms who achieved the defined response in PPBC at each of 4, 8 and 12 weeks.  Table 2 shows data for the proportion of patients achieving  50% and 100% reduction in OAB symptoms who have reached the MID for the OAB-q symptom bother score and QOAB-q HQRL total score.
Interpretation of results
At week 4, 64.0 – 76.7% of patients who had achieved a significant change in PPBC had a 50% reduction in UUI. At week 12 this proportion had increased to between 80 – 87.9%, with those being exposed to fesoterodine treatment experiencing a significant reduction in PPBC at numerically higher rates. The association between UUE and PPBC response was much less strong, with only 3.0% of patients experiencing a 50% reduction in UUE showing a response in PPBC at 4 weeks. Of patients with a normalization of DMF at week 4, only 40.2 – 52.9% reported an improvement in PPBC; by week 12 , these proportions had risen to between 49.1 – 60%. At 12 weeks 80% of treated patients reporting a significant improvement in quality of life, had achieved a 50% reduction in UUI whereas only 40.7 – 54.3% of patients reporting a response in OAB-q HRQL total scores had achieved a 50% response in UUE
Generally, for each category of treatment response, the proportion of people who reached either 50% or 100% symptom relief the minimal important difference in OAB-q symptom bother score or health related quality of life score increased over the 12 weeks of the study, their PROM responses appear to occur earlier, highlighting the need to give time for drug therapy to reach its maximum benefit.
Concluding message
OAB treated patients reporting a significant response to patient reported outcome measures report varying degrees of symptom relief at different time points.  Maximum relief appears to take at least 12 weeks to be achieved.
Figure 1
Figure 2
Disclosures
<span class="text-strong">Funding</span> Statistical support was provided by Pfizer Canada <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics not Req'd</span> Secondary analysis of existing anonymized data <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes