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Overactive Bladder and Incontinence
Flexible-dose Fesoterodine and Treatment Satisfaction
a report by
Jean Jacques Wyndaele
Professor and Chairman, Department of Urology, University of Antwerp and University Hospital Antwerp
Overactive bladder syndrome (OAB) is a prevalent condition with a heavy pad test and Incontinence Quality of Life Questionnaire measures in double-
burden on quality of life (QoL).
1
Urgency is considered to be the main blind, placebo-controlled studies that evaluated duloxetine for the treatment
symptom driving most of the other symptoms of OAB.
2
Urgency can be of predominant stress urinary incontinence. This established the construct
considered as the highest possible grade of desire to void.
3
Reporting has validity of these two global assessment questions for baseline severity and
proved useful and reliable in patients and healthy volunteers if the treatment response.
10
A urinary-incontinence-specific measure of quality of
terminology ‘strong desire to void that could not be held for more than life (I-QOL) has been adapted successfully into different languages and its
five minutes’ is used. Such sensations have been described by women with cross-sectional psychometric properties have been confirmed.
11
different types of incontinence, including urgency incontinence.
4
Although antimuscarinic agents are the pharmacological mainstay of
The most widely used definition of OAB is from the International OAB treatment, efficacy and tolerability vary among agents and patients.
Continence Society (ICS): “urgency with or without urgency incontinence Recent studies show that antimuscarinic drugs act directly, at least in
usually with daytime frequency and nocturia”.
5
This definition does not part, on the sensory innervation of the lower urinary tract. This could
rely on urodynamic observations for a diagnosis. It describes symptoms mean that sensory symptoms are influenced directly by these drugs.
and signs driving the daily life of patients. In clinical practice, improving
these symptoms and signs is the main goal of treatment. Fesoterodine is a new approved drug for the treatment of OAB.
12
It
functions as an orally active prodrug that is converted to the active
However, in clinical practice the physician’s assessment of the disease metabolite 5-hydroxymethyltolterodine (5-HMT), a muscarinic receptor
burden of OAB has been shown to be inaccurate and non-reproducible. In antagonist, by non-specific esterases. Fesoterodine is primarily eliminated
contrast, psychometrically robust self-completion questionnaires provide a as inactive metabolites, along with significant renal excretion as the
valid, reproducible and rapid assessment of patient-reported disease impact unchanged active metabolite 5-HMT. Fesoterodine is indicated for use at
that can elicit the effect of symptoms, and are also useful for the evaluation doses of 4 and 8mg once daily (QD). In clinical studies both doses of
of the efficacy of an intervention. Many questionnaires have been developed fesoterodine were consistently superior to placebo in improving the
to assess the QoL impact of OAB, and these have been selectively evaluated symptoms of OAB, with 8mg/day having significantly greater effects than
by consecutive International Consultations on Incontinence (ICI). Generic 4mg/day. Due to the esterase-mediated cytochrome P450-independent
instruments measure very broad aspects of health, but are less sensitive to formation of 5-HMT and involvement of multiple metabolic and renal
clinically relevant change in conditions such as OAB. Condition-specific excretion pathways in the elimination of 5-HMT, the effects of patient-
questionnaires offer greater sensitivity and responsiveness to change in the intrinsic and -extrinsic factors on the pharmacokinetics of fesoterodine are
assessment of QoL in specific patient groups. Single-item global assessment only modest, with some two-fold higher 5-HMT exposure. Therefore, in
questionnaires are useful in conditions such as OAB that have multiple and contrast to tolterodine, no reduction of fesoterodine dosage is required
varied symptoms, and reflect an individual’s needs, concerns and values. under conditions of reduced elimination. In most cases of drug interaction
Patient-derived outcome measures are used in real-world clinical practice, or renal/hepatic impairment, the fesoterodine dose may be increased to
clinical trials, health economic research and healthcare planning.
6
8mg/day based on individual patient response, or patients may be required
to remain at the initial recommended dose of 4mg/day.
13
The use of composite end-points determining response rates to
pharmacotherapy provides a relevant measure of patient benefits and
Jean Jacques Wyndaele is a Professor and Chairman of the
impact on QoL. In previous studies, response has been defined as a reduction
Department of Urology at the University of Antwerp and
in symptoms. In the King’s Health Questionnaire (KHQ), a reduction by 50%
University Hospital Antwerp. He is Chair of the Animal
or more in all baseline symptoms or resolution of urgency and more than
Research Lab of the Urological Department at the University
of Antwerp and Vice Dean of the Faculty of Medicine at the
one other symptom were found to be most effective at capturing QoL
same institution. Professor Wyndaele holds several offices in
changes.
7
Alterations of ‘bother’ may better reflect patient-relevant
international and national organisations. He is Editor in
Chief of Spinal Cord and a member of several Editorial
outcomes in OAB treatment than alterations in the number of symptom
Boards. He is a Fellow of the International Spinal Cord
episodes.
8
The Urgency Severity and Impact Questionnaire (USIQ) has two Society and the European Board of Urology, a faculty member of the European School of
parts – symptom severity (USIQ-S) and related QoL (USIQ-QOL) – and has
Urology and a member of many professional societies. Professof Wyndaele is the author or
co-author of 223 publications in peer-reviewed international and national journals and 26
been proved to be easily understandable and to offer adequate validity.
9
chapters in books. He holds qualifications as a Medical Doctor, a Specialist in Urology, Doctor
in Science, Specialist in Rehabilitation and Ph Doctor in Urology.
The Patient Global Impression of Severity and of Improvement question
E:
wyndaelejj@skynet.be
responses correlated significantly with incontinence episode frequency, stress
© TOUCH BRIEFINGS 2008 57
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