Symptom relief from OAB: what an"average" patient might expect: data from a pooled analysis of Fesoterodine treated patients

LaBossiere J R1, Fernet M2, Herschorn S1, Carlsson M2, Oelke M3, Wagg A4

Research Type

Clinical

Abstract Category

Overactive Bladder

Abstract 151
Open Discussion ePosters
Scientific Open Discussion ePoster Session 7
Wednesday 29th August 2018
12:20 - 12:25 (ePoster Station 9)
Exhibition Hall
Overactive Bladder Incontinence Pharmacology
1. University of Toronto, Toronto, Ont. Canada, 2. Pfizer Canada, Montreal, QC, Canada, 3. St. Antonius-Hospital Akademisches Lehrkrankenhaus der WWU Münster, Gronau, 4. University of Alberta, Edmonton, Alberta, Canada
Presenter
S

Sender Herschorn

Links

Poster

Abstract

Hypothesis / aims of study
Overactive bladder (OAB) is a troublesome condition for many in the population with estimates suggesting that up to 19% of adults >40years of age have OAB [1].   OAB is associated with adverse health and quality of life outcomes such as urinary tract infection, falls, depression and for those with advanced age, an increased likelihood of institutionalisation. Severity of symptoms and urgency incontinence drive patients to seek treatment. Those who fail to gain adequate symptomatic relief with lifestyle and behavioural measures are often managed with  pharmacotherapy based on current evidence-based guidelines. Data from randomized clinical trials (RCT) support the use of pharmacotherapy in symptom control but are limited in that the results only describe the average change in index symptoms across the sample of patients entering the study.  For newer treatments there is still a dearth of data on what response to treatment an individual patient might expect given their symptoms at presentation, a question often posed to primary care practitioners who are commonly charged with initiating drug therapy.  Using pooled trial data, this study sought to characterize patient symptom response following treatment with fesoterodine.
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)
•	3 symptoms, reduction in all of urgency, 24 hr frequency and UUI
Results
There were 6689 patients included in all studies (fesoterodine 4mg, 1373, fesoterodine 8mg 3263, placebo 2053). Demographic details and baseline symptom indices at trial entry are shown in Table 1.The proportions of patients experiencing a 50% and 100% reduction in their symptoms at week 4, 8 and 12 in for UUE, UUI, DMF, NMF and all variables according to treatment exposure are shown in Table 2. Overall safety of fesoterodine did not differ from that demonstrated in source trials.
Interpretation of results
There was an increase in symptom response in patients managed with either 4 or 8 mg of fesoterodine compared to treatment with placebo. At all time points, the decrease in UUE was noticeably smaller than that in UUI and total abolition of UUE was seldom seen.  On fesoterodine 8mg at 4 weeks, approximately a quarter of patients experienced a normalization in NMF and nearly a half experienced normalization of DMF.  At 8 and 12 weeks when treated with fesoterodine 8mg, a minority of patients experienced a total resolution of UUE whereas at these 2 timepoints, 23.5 and 53.2% respectively experienced total resolution of UUI When treated with fesoterodine 4mg, 16.3 and 38.9% experienced total resolution of UUI at week 8 and 12, respectively.    Approximately 40 – 50% of people will normalize DMF at week 12. Fesoterodine treatment is associated with a marginal, and clinically insignificant proportional increase in normalization of NMF at week 12 over that compared to placebo. Total resolution of all symptoms was seldom achieved, regardless of timing or dose of fesoterodine. These data provide useful information for patients presenting for treatment in order to convey realistic expectations of symptom relief.
Concluding message
This study describes symptom response following fesoterodine for OAB and provides clinically relevant information useful for individualized patient counselling regarding expectations from drug treatment
Figure 1
Figure 2
References
  1. Eur Urol. 2006 Dec;50(6):1306-14
Disclosures
Funding Statistical support was provided from Pfizer Canada Clinical Trial No Subjects Human Ethics not Req'd Secondary analysis pf previously approved data Helsinki Yes Informed Consent Yes