BJUI
Persistence with prescribed antimuscarinic
therapy for overactive bladder: a UK experience
BJU INTERNATIONAL
Adrian Wagg, Gerhard Compion*, Amanda Fahey† and Emad Siddiqui†
University of Alberta, Edmonton, AB, Canada, *Astellas Pharma Europe, and †Astellas Pharma UK, Staines, UK
Accepted for publication 9 November 2011
Study Type – Therapy (prevalence)
Level of Evidence 2b
OBJECTIVES
• To describe the level of persistence for
patients receiving antimuscarinics for
overactive bladder (OAB) over a 12-month
period based on real prescription data from
the UK.
• To investigate patterns of persistence
with oral antimuscarinic drugs prescribed
for OAB, across different age groups.
PATIENTS AND METHODS
• UK prescription data from a longitudinal
patient database were analysed
retrospectively to assess persistence with
darifenacin, flavoxate, oxybutynin
(extended release [ER] and immediate
release [IR]), propiverine, solifenacin,
tolterodine (ER/IR) and trospium.
• Data were extracted from the medical
records of >1 200 000 registered patients
via general practice software, and
anonymized prescription data were collated
for all eligible patients with documented
OAB (n = 4833).
• Data were collected on patients who
started treatment between January 2007
and December 2007 and were collected
up to December 2008, to allow each
patient a full 12-month potential
treatment period. Failure of persistence was
declared after a gap of at least 1.5 times
the length of the period of the most recent
prescription.
INTRODUCTION
Overactive bladder (OAB) is a clinical
diagnosis characterized by the presence
of lower urinary tract storage symptoms,
©
What’s known on the subject? and What does the study add?
Persistence with long-term medication in chronic diseases is typically low and that for
overactive bladder medication is lower than average. Sub-optimal persistence is a
major challenge for the successful management of overactive bladder.
Using UK prescription data, persistence was generally low across the range of
antimuscarinics. Patients aged 60 years and above were more likely to persist with
prescribed oral antimuscarinic drugs than younger patients (40–59 years). Solifenacin
was consistently associated with the highest rate of persistence compared with the
other antimuscarinics included in the study
• The analysis included only patients who
were new to a course of treatment (i.e.
who had not been prescribed that
particular treatment or dosage for at least
6 months before the study period).
• In a sub-analysis stratified by age,
patients aged ≥60 years were more likely
to persist with prescribed therapy over the
12-month period than those aged <60
years.
RESULTS
CONCLUSIONS
• The number of patients prescribed each
antimuscarinic drug varied from 23 for
darifenacin to 1758 for tolterodine ER.
• The longest mean persistence was
reported for solifenacin (187 days versus
77−157 days for the other treatments).
• At 3 months, the proportions of patients
still on their original treatment were:
solifenacin 58%, darifenacin 52%,
tolterodine ER 47%, propiverine 47%,
tolterodine IR 46%, oxybutynin ER 44%,
trospium 42%, oxybutynin IR 40%,
flavoxate 28%.
• At 12 months, the proportions of
patients still on their original treatment
were: solifenacin 35%, tolterodine ER 28%,
propiverine 27%, oxybutynin ER 26%,
trospium 26%, tolterodine IR 24%,
oxybutynin IR 22%, darifenacin 17%,
flavoxate 14%.
particularly urinary urgency – a sudden
compelling desire to pass urine that is
difficult to defer [1]. The ICS defines
OAB as ‘urgency, with or without
urgency incontinence, usually with
• Twelve months after the initial
prescription, persistence rates with
pharmacotherapy in the context of OAB are
generally low.
• Solifenacin was associated with higher
levels of persistence compared with other
prescribed antimuscarinic agents.
• Older people are more likely than
younger patients to persist with prescribed
therapy. Further studies are required to
understand this finding and why patients
are more likely to persist with one drug
rather than another.
KEYWORDS
persistence, overactive bladder,
antimuscarinic drugs, solifenacin
increased daytime frequency and nocturia’
[2].
OAB is common in men and women, and is
a chronic condition requiring long-term
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WAGG ET AL.
medical management and lifestyle changes
[3]. In one population-based survey of men
and women aged ≥18 years in the USA, OAB
was estimated to affect 16–17% of the
adult population [4]. Similarly, the results of
a survey of men and women aged ≥40 years
in Europe estimated the overall prevalence
of OAB in this population at 16.6%, with a
19% prevalence in the UK alone [5]. The
European Association of Urology estimates
the prevalence of OAB as varying from 10%
to 26% in men, and from 8% to 42% in
women, with a clear trend of increasing
prevalence with advancing age. OAB often
occurs simultaneously with other LUTS [6]
and most older individuals have at least one
such symptom, but OAB constitutes a
specific sub-set of storage-phase symptoms
[1].
The potential negative impact of OAB on
quality of life, through its effects on
day-to-day activities, is well established [1].
Patients with OAB tend to curtail their
participation in social activities and to
isolate themselves. Nocturia is associated
with sleep disruption, which decreases
quality of life for patients and their partners
[7]. OAB is also associated with other
co-morbidities, including fractures related to
falls, urinary tract infections and skin
infections [3,8]. These are distressing to
patients and can be costly to treat; it is
therefore not surprising that successful OAB
therapy can be cost-effective [3,9].
The drugs most commonly prescribed for
the treatment of OAB are antimuscarinics
[10]. These drugs decrease OAB symptom
severity, but some patients experience
adverse effects, most commonly dry mouth
[11,12]. Furthermore, it may take several
weeks for antimuscarinics to show their full
benefit and maximum clinical efficacy
[13,14]. Many find the balance of adverse
effects against efficacy benefits to be
unsatisfactory, and discontinue therapy
[3,10]. However, the tolerability of adverse
effects increases with prolonged usage of
antimuscarinic drugs for OAB, by which time
the efficacy of the therapy can also be
perceived [13,15].
For pharmacotherapy to be beneficial in
chronic conditions such as OAB, adherence
and persistence are essential [16]. Adherence
(or compliance), defined as the extent to
which a patient takes their prescribed
medication at the correct interval and dose
1768
is the extent to which a patient continues
treatment for the prescribed duration,
measured either as the mean number of
days between treatment initiation and
discontinuation, or as the percentage of
patients who persist with therapy for a
minimum fixed number of days [17,18].
Patients with poor medication adherence
have increased rates of morbidity and
mortality, and poor adherence is itself
associated with increased healthcare costs
[19,20].
Persistence with long-term medication in
chronic diseases is typically low (about 50%)
[21]. In 2003, the World Health Organization
identified medication non-adherence (or
non-persistence) as a leading cause of
preventable morbidity, mortality and
healthcare costs [22], and a more recent
report by the New England Healthcare
Institute estimated the avoidable burden
to the US healthcare system of nonpersistence, along with sub-optimal
diagnosis, prescribing and medication
administration, to be $290 billion per year,
or 13% of total healthcare expenditures
[23].
Sub-optimal persistence is therefore a major
challenge for the successful management of
OAB [24]. The chronic nature of the
condition means that effective treatment
must be long term and continuous, and
must be taken as prescribed. Persistence
requires an acceptable balance between
tolerability and efficacy, and unsurprisingly,
is one of the critical predictors of outcomes
in chronic conditions [15,25–27]. Persistence
with therapy is important for sustained
symptom control in OAB and consequent
quality of life, and prompt initiation of
optimal OAB treatment may delay or even
prevent progression of the disease process
[3,28].
Persistence at 12 months is much lower in
routine practice than in the clinical trial
setting, where the rate of persistence is
usually >80% [15,24]. This is probably
because the intensive follow-up and care
involved in a clinical trial encourage
adherence; trial subjects also may not be
representative of the patients seen in clinical
practice [24]. Additionally, randomized trials
generally underestimate adverse effects and
problems with poor compliance/persistence
compared with real-life settings [29]. In
contrast, in studies of clinical practice, many
patients quickly discontinue OAB medication,
part because of adverse effects [27,30,31].
Another study of US Medicaid patients
found that only 32–44% of those prescribed
OAB medications continued treatment
beyond 30 days, eventually declining to a
5–9% persistence rate at 1 year [25].
Similarly, a more recent study examining
OAB medication compliance in a healthcare
system in which patients do not pay for
medication reported that 35% of patients
did not refill a prescription for OAB
medication over the 4 years evaluated [26].
Consistent with these previous reports,
in a recent systematic review of studies
published since 1998 on the treatment of
OAB syndrome with anticholinergic therapy,
rates of discontinuation from medical
claims studies ranged from 43% to 83% of
patients discontinuing medication within the
first 30 days, with rates continuing to rise
over time [32]. Consistently, two similar
independent retrospective analyses of
prescription data conducted in Denmark
and Sweden – the first over a 7-year period
and the second over a 1.5-year period
– reported similar continuation rates of
<50% at 6 and 4 months, respectively, and
<25% at 1 year [33,34]. Hence, in real-life
settings versus in clinical trials, persistence
with OAB medication appears to be
sub-optimal.
Studies evaluating persistence are not
limited to the treatment of OAB. The
effectiveness of bisphosphonates in
osteoporosis is compromised by poor
adherence to treatment, because a
significant proportion of patients abandon
their treatment within 7 months of initiation
and more than half stop the treatment
within the first year. This is mostly the result
of adverse effects, difficulty with drug
administration and formulation [35–37].
Numerous studies have also been conducted
evaluating the hindrances with
antihypertensive drug adherence and
persistence in controlling high blood
pressure. Typically, only about 50% of
patients for whom antihypertensive drug
treatment is initiated persist on treatment 1
year later [18,38]. Overall, drug dose and
formulation are important determinants of
persistence, but patient awareness and
education/support could also have an
impact on patients’ understanding of the
importance of taking their medication
continuously to control their symptoms.
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PERSISTENCE WITH ANTIMUSCARINIC THERAPY IN OAB
eligible patients with OAB (n = 4833),
eliminating any risk of sampling bias.
TABLE 1 Number of prescriptions per patient and duration of therapy (all patients)
Treatment
Darifenacin (n = 23)
Flavoxate (n = 89)
Oxybutynin ER (n = 590)
Oxybutynin IR (n = 1371)
Propiverine (n = 97)
Solifenacin 5 mg (n = 1258)
Solifenacin 10 mg (n = 332)
Tolterodine ER (n = 1758)
Tolterodine IR (n = 482)
Trospium (n = 352)
Prescriptions per
patient (n)
3.6
2.6
4.9
4.1
5.9
4.7
6.6
4.5
4.7
4.5
Duration of
therapy (days)
135.9
77.4
146.7
119.3
141.1
158.7
216.0
156.7
151.7
138.5
Oxybutynin data are for generic prescriptions. ER, extended release; IR, immediate release.
One study compared adherence and
persistence in six commonly used chronic
diseases and associated medication classes:
glaucoma (prostaglandin analogues),
hyperlipidaemia (statins), osteoporosis
(bisphosphonates), type 2 diabetes (oral
antidiabetic drugs), hypertension
(angiotensin II receptor blockers) and OAB
(antimuscarinics). Six-month persistence
rates and mean 12-month adherence rates
were lowest for OAB medications (28% and
35%, respectively) [39]. In comparison, about
57% of hypertensive patients continued past
the first year after receiving their initial
prescription [20,40].
persistence were lower among Black than
White patients [25].
The objective of this study was to estimate
persistence rates for OAB patients taking
antimuscarinic agentss based on UK NHS
prescription data, where 88% of all
prescriptions are free to the patient, and to
investigate patterns of persistence with oral
antimuscarinic drugs prescribed for OAB
across different age groups over a
12-month period. Normally, prescriptions in
UK practice are given on a monthly basis.
MATERIALS AND METHODS
The reasons underlying these low rates of
persistence for OAB therapy in clinical
practice are not clear. Few studies have
reported either the predictors or the
patient-reported reasons for OAB medication
discontinuation [20,41]. In several
retrospective database studies, rates of
adherence or persistence were higher in
patients taking extended-release
formulations of tolterodine or oxybutynin
than in those taking immediate-release
formulations [16,21,25], although in one
study this effect appeared to be the result
of better adherence and persistence in older
than in younger patients [25]. Consistent
with the latter finding, a retrospective study
of claims data identified some predictors of
OAB medication discontinuation, such as
younger age (<65 years) and taking multiple
daily doses, or taking an immediate-release
formulation [16]. Finally, another study
found that rates of adherence and
©
UK prescription data from a longitudinal
patient database were analysed
retrospectively to assess persistence with
darifenacin, flavoxate, oxybutynin (extended
release [ER] and immediate release [IR]),
propiverine, solifenacin, tolterodine (ER/IR)
and trospium. Flexible dosing regimens
existed for solifenacin (5/10 mg), darifenacin
(7.5/15 mg) and oxybutynin ER and IR
(5/10 mg and 2.5/3/5 mg, respectively).
Patients started treatment between January
2007 and December 2007, and data were
collected up to December 2008, to allow
each patient a full 12-month potential
treatment period. Prescription data were
provided by CSD Ltd (Chertsey, UK). Data
were sourced from the medical records of
>1 200 000 currently registered patients via
general practice software, and anonymized
prescription data were collated for all
Only patients new to a course of treatment
(i.e. who had not been prescribed a
particular treatment or dosage for at least
6 months before the study period) were
included in this analysis. Therefore, patients
were included only if they had been
receiving a different antimuscarinic or the
same antimuscarinic but a different dosage
during the previous 6 months. Patients were
excluded if they had already been prescribed
the specific antimuscarinic or dosage
referred to in the analysis at some point in
the last 6 months before the evaluation
period.
Persistence was defined as the mean
number of days that a patient remained on
therapy [17,18]. Each patient was tracked
until they ceased to be continuously treated,
with a break in therapy defined as an
interval >1.5 times the expected number of
days of therapy of the previous prescription,
from the start of the script. Patients who
ceased to be continuous but who restarted
at a later date within the reference period
were allowed back into the analysis at the
point which they restarted. No formal
statistical analyses were performed.
RESULTS
Over the 12 months of the study, 4833
patients were prescribed the included
antimuscarinic agents. The most prescribed
drug during the 12-month period was
tolterodine ER (1758 patients), followed by
solifenacin (1381 patients) and oxybutynin
IR (1371 patients) (Table 1). This is largely
reflective of the UK market at the time [42].
The mean number of prescriptions per
patient was highest for solifenacin (10 mg;
6.6 prescriptions per patient), followed by
propiverine (5.9), oxybutynin ER (4.9),
solifenacin (5 mg) and tolterodine IR
(both 4.7). Solifenacin 10 mg also had the
highest mean duration of therapy per
patient (216 days), followed by solifenacin
5 mg (158.7), tolterodine ER (156.7),
tolterodine IR (151.7), oxybutynin ER (146.7),
propiverine (141.1), trospium (138.5),
darifenacin (135.9), oxybutynin IR (119.3)
and flavoxate (77.4).
Consistent with previous reports, persistence
with all antimuscarinic agents prescribed
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WAGG ET AL.
200 187
Days
119
120
77
80
FIG. 1.
Mean time that patients
remained on therapy with each
antimuscarinic. Data are for
combined doses for each
antimuscarinic. Numbers are for
patients starting treatment.
40
So
li
To fena
lte
cin
ro
(n
di
n
=
e
To
lte ER 138
1)
(n
ro
=
Ox din
e I 175
yb
R
ut
(n 8)
yn
=
in
48
Pr ER
(n 2)
op
=
ive
59
r
0)
Tro ine
(
sp
n=
iu
97
m
Da
Ox rife (n = )
n
yb
3
ut acin 52
)
yn
(
n
in
=
IR
23
)
Fla (n =
vo
xa 137
1
te
(n )
=
89
)
0
Antimuscarinic drug
100
solifenacin (n = 1381)
tolterodine ER (n = 1758)
tolterodine IR (n = 482)
oxybutynin ER (n = 590)
oxybutynin IR (n = 1371)
propiverine (n = 97)
trospium (n = 352)
darifenacin (n = 23)
flavoxate (n = 89)
80
60
40
20
0
FIG. 2.
Percentage of patients remaining
on each antimuscarinic over 12
months. Data are for combined
doses for each antimuscarinic.
Numbers are for patients starting
treatment.
1 2 3 4 5 6 7 8 9 10 1112
Months
FIG. 3. Twelve-month persistence with each prescribed antimuscarinic therapy, analysed by individual
drug.
100
90
80
Patients, %
70
60
50
40–49 years
40
50–59 years
30
60–69 years
20
70–79 years
10
>80 years
xa
t
Ox
yb
ut
cin
na
ife
Fla
vo
n
(n
=
23
)
e(
n=
yn
in
Ox
89
ER
yb
)
ut
(
n
yn
=
in
59
IR
0)
(n
Pr
=
op
So
1
ive
lif
37
en
1)
rin
ac
e
in
(n
So
5
=
lif
m
97
en
g
)
ac
(n
in
=
12
10
To
58
m
lte
)
g
ro
(n
di
=
ne
3
32
ER
To
)
lte
(n
ro
=
di
1
75
ne
8)
IR
(
n=
Tro
sp
48
iu
2)
m
(n
=
35
2)
0
Da
r
Sub-analyses of the 4833 patient
prescription records by age and drug dosage
were also performed. Patient numbers
tended to increase with age and peak in the
60–79-year age groups (Table 2). In most
cases, patients aged ≥60 years were more
likely to persist with prescribed therapy
over the 12-month period than younger
patients (Fig. 3), for example patients aged
≥60 years on oxybutynin IR, propiverine,
solifenacin (5/10 mg), tolterodine ER and
trospium. However, this was not the case
for oxybutynin ER, where persistence
dropped consistently from age groups
50–59 through to 70–79 years, despite the
number of patients on this treatment
increasing through these age groups. With
oxybutynin IR, propiverine and trospium,
persistence peaked at 60–69 years and
dropped in the age group 70–79 years. At
12 months, patients receiving solifenacin
10 mg were most likely to persist with
therapy (up to 56.6% of 76 patients aged
70–79 years).
157 152
147 141
139 136
160
Patients, %
was generally low over the evaluation
period. The longest persistence (defined as
the mean number of days a patient
remained on a particular therapy) was
associated with solifenacin 5/10 mg (187
days; Fig. 1). At 3 months, 58% of patients
who started on solifenacin (5/10 mg) were
still on treatment (Fig. 2) compared with
darifenacin (52%), tolterodine ER and
propiverine (both 47%), tolterodine IR (46%),
oxybutynin ER (44%), trospium (42%),
oxybutynin IR (40%) and flavoxate (28%). At
6 months, the persistence with solifenacin
treatment was 46%, compared with
tolterodine ER and propiverine (both 36%),
oxybutynin ER (35%), tolterodine IR and
trospium (both 33%), darifenacin (30%),
oxybutynin IR (29%) and flavoxate (16%). At
12 months, 35% of patients were still
receiving solifenacin (Fig. 2), compared with
tolterodine ER (28.2%), propiverine (26.8%),
oxybutynin ER (26.1%), trospium (25.9%),
tolterodine IR (24.1%), oxybutynin IR
(21.7%), darifenacin (17.4%) and flavoxate
(13.5%).
DISCUSSION
OAB requires long-term management to
control symptoms and improve patient
quality of life. Although antimuscarinics are
the cornerstone of pharmacotherapy for
OAB syndrome in men and women,
1770
Antimuscarinic drug
persistence with prescribed therapy in
Europe, including in the UK, remains low
[33,34]. Furthermore, persistence rates vary
between antimuscarinics: although this may
be partly linked to efficacy and tolerability
differences, persistence is generally better
with extended-release and once-daily
formulations [16,25].
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PERSISTENCE WITH ANTIMUSCARINIC THERAPY IN OAB
TABLE 2 Twelve-month persistence rates with prescribed antimuscarinic medication according to
patient age
Treatment
Darifenacin (n = 23)
Total patients treated
Percentage on therapy at 12 months
Flavoxate (n = 89)
Total patients treated
Percentage on therapy at 12 months
Oxybutynin ER (n = 590)
Total patients treated
Percentage on therapy at 12 months
Oxybutynin IR (n = 1371)
Total patients treated
Percentage on therapy at 12 months
Propiverine (n = 97)
Total patients treated
Percentage on therapy at 12 months
Solifenacin 5 mg (n = 1258)
Total patients treated
Percentage on therapy at 12 months
Solifenacin 10 mg (n = 332)
Total patients treated
Percentage on therapy at 12 months
Tolterodine ER (n = 1758)
Total patients treated
Percentage on therapy at 12 months
Tolterodine IR (n = 482)
Total patients treated
Percentage on therapy at 12 months
Trospium (n = 352)
Total patients treated
Percentage on therapy at 12 months
Age group (years)
40–49
50–59
1
N/A
11
18.2
5
20.0
10
N/A
60–69
70–79
≥80
7
14.3
3
66.7
4
N/A
18
11.1
20
15
20
25
65
24.6
72
26.4
132
25.8
113
23.9
114
27.2
124
16.1
171
21.6
210
27.1
287
22.3
302
24.2
7
28.6
16
18.8
19
36.8
25
32
23
21.7
143
21.7
199
25.1
259
32.0
313
31.3
225
25.3
46
32.6
59
37.3
74
45.9
76
56.6
51
43.1
211
19.0
271
26.2
375
28.5
400
34.8
346
32.1
52
13.5
65
24.6
77
15.6
113
36.3
123
27.6
26
15.4
63
27.0
63
31.7
97
23.7
74
29.7
Oxybutynin data are for generic prescriptions. ER, extended release; IR, immediate release.
The objective of the present study was to
use real prescription data to extrapolate
persistence patterns for antimuscarinics
among patients in the UK across different
age groups, over a 12-month period. As in
previous studies, persistence was generally
low for all the medications analysed, and
patients aged 60 years and above were more
likely to persist with prescribed oral
antimuscarinic drugs than younger patients
(40–59 years). Although more patients were
prescribed tolterodine ER overall, solifenacin
10 mg was associated with the greatest
mean number of repeat prescriptions per
patient.
In the age group sub-analysis, patients
taking solifenacin 10 mg had the highest
©
persistence with therapy, particularly those
aged >60 years. These findings are
consistent with a long-term open-label
extension study evaluating the efficacy and
tolerability of solifenacin 5 mg and 10 mg,
in which 81% of patients completed 40
weeks of treatment, with only 4.7%
discontinuing treatment owing to adverse
events. In the present study at 3 months,
solifenacin was associated with the highest
rate of persistence, whereas oxybutynin IR
was associated with the lowest. At 12
months, solifenacin continued to be
associated with the highest level of
persistence, whereas darifenacin was
associated with the lowest persistence.
Although solifenacin was consistently
associated with the highest rate of
persistence compared with the other
antimuscarinics included in the study,
persistence was generally low for all the
antimuscarinics during the 12-month
evaluation period. These results are
consistent with a recent retrospective study
conducted in the Netherlands, investigating
persistence with treatment with four
commonly prescribed antimuscarinics
(flavoxate, oxybutynin IR, tolterodine IR and
solifenacin) by analysing prescription data
over a 9-month period. The study found
that, although persistence with treatment
declined rapidly during the first 4 weeks,
patients who started on solifenacin had
consistently higher levels of persistence
throughout the study period (47% of
patients who started on solifenacin were
still on treatment at 3 months, versus
24–38% for the other antimuscarinics
evaluated) [43].
Patients who were initially prescribed
solifenacin 5 mg and were later prescribed a
dose increase to solifenacin 10 mg were
considered non-persistent for solifenacin
5 mg at that time point, and treated as a
new patient for the solifenacin 10 mg
group. This limitation of the study applies to
all antimuscarinics with more than one dose
or strength. We did not report results for
different strengths of antimuscarinics other
than solifenacin in this study. Prescription
numbers for darifenacin were too small to
be split by strength and the availability of
multiple strengths for oxybutynin ER/IR
complicated interpretation of the data, so
the results were combined. Similarly, data
for short-acting antimuscarinics requiring
multiple dosing were also combined to
facilitate data analysis. No results are
available for fesoterodine because the drug
was not available in the UK at the time of
this analysis.
Although these results are important, the
study has some limitations. It was originally
conceived as a post-marketing analysis of
persistence, so it did not address a
prospectively defined hypothesis, hence the
descriptive nature of the analysis and the
absence of comparative statistics. We were
unable to ascertain treatment naivety using
this method, which would have required
a detailed search of any medication
prescription ever given to an individual.
There is also a paucity of information on
patients’ previous therapies, their symptom
severity at enrolment, whether bladder
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WAGG ET AL.
training was used alongside antimuscarinic
therapy and whether successful conservative
and behavioural therapies resulted in
cessation of treatment. We may also have
assumed dose escalation for some therapies,
so non-persistence at the lower dose of
medication in these circumstances may have
been underestimated. However, this
limitation applied to all antimuscarinics
studied where more than one dose is
licensed. The small number of people in
some prescription categories by age should
also lead to caution in interpretation of the
results for drugs in those categories.
Other aspects that limit our interpretation
of these data are intermittent versus
continuous therapy, and drug holidays
(structured treatment interruptions to
re-establish efficacy or avoid adverse effects
for a short period, which are common
practice in diseases such as HIV infection).
Although continuous treatment with
antimuscarinics is recommended to obtain
maximum efficacy, in real-life situations,
some patients may take drug holidays at
their own discretion. Intermittent therapy
refers to patients who only return for repeat
prescriptions once their symptoms have
returned or worsened (i.e. deliberate poor
compliance). Patients might use medication
only when their symptoms are likely to
cause bother, such as on long journeys, or at
social events [24]. Similarly, drug holidays
could have adversely affected our results.
Finally, in the present study, reasons for
discontinuing treatment were not recorded,
which limits our interpretation of
persistence failure and any further analysis.
We also cannot answer the question as to
why older patients have higher persistence
compared with younger ones. Previous
retrospective studies have also found that
age correlates positively with persistence
[16,25], consistent with our findings. The
reasons for this have not been fully
elucidated, but several hypotheses seem
plausible. Older patients may have fewer
time pressures, or be used to taking other
medications, or their more severe experience
of OAB may mean that they derive more
benefit from treatment. In contrast, one
previous longitudinal cohort study of older
(>65 years) patients with OAB found that
patient age and co-morbidities had a
negative influence on treatment adherence,
although the influence of individual
antimuscarinic therapy on adherence and
1772
healthcare use was not examined [24]. A
more recent publication assessed the effect
of age on the efficacy and tolerability of
fesoterodine (4 and 8 mg), and showed that
efficacy was lower and the incidence of
adverse effects was higher in patients aged
>65 years. This may suggest that older
people require more medication, rather than
less, to control their symptoms, even if their
symptoms are of a similar magnitude to
those of their younger counterparts [44].
Older people may, of course, simply be more
likely to do as their clinician instructs. The
apparent decrease in persistence for those
>80 years of age, although still higher seen
across all of the antimuscarinics, is likely to
be multifactorial. This may reflect active
decisions to stop medication on behalf of
prescribers because of the pervasive,
although sometimes misplaced, belief that
older people do not do well on these
medications; a diminution of the importance
of this condition, compared with other
co-morbid conditions seen as ‘more serious’
or an effect of the higher rate of adverse
effects reported by this age group. None of
these speculated reasons can be answered
by our study, but each is worthy of further
investigation.
In surveys evaluating patient-reported
reasons for discontinuing antimuscarinic
prescription medications for OAB,
expectations about treatment efficacy and
adverse effects were the most important
factors, with 45.4% of patients reporting
unmet treatment expectations as the reason
for discontinuation [20,41]. Consistent with
these surveys, a recently published 12-week
observational study investigating factors
that motivate physicians and patients to
change their OAB treatment found that
reasons for last treatment change included
lack of efficacy (60%) and adverse events
(24%) [45]. Interventions promoting realistic
expectations about treatment efficacy and
adverse effects might therefore enhance
adherence and persistence [41].
It is important for physicians to identify the
most appropriate therapy to meet their
patients’ needs, to educate patients about
the nature of their disease, and to provide
regular support during the course of their
treatment, thereby encouraging and
improving persistence with therapy. Patient
support may be achieved through external
programmes that complement patient–
physician interactions [20]. For example, a
12-week Patient Support Programme in the
UK, available to patients with OAB who are
prescribed solifenacin, has helped to
improve and maintain persistence with
solifenacin therapy (≥76% of patients were
still taking solifenacin at 3–12 months
after enrolment on the patient support
programme) [46]. There are no other
published data on the effectiveness of
patient support programmes for OAB in the
UK and at the time of this study, none was
in operation. Subsequently, a support
programme for fesoterodine has been
introduced by Pfizer. Patient support
programmes have also been successful at
improving persistence in other therapeutic
domains, for example in the context of
osteoporosis medication in postmenopausal
women. The PERSIST study showed that
once-monthly dosing with ibandronate,
coupled with the ibandronate patient
support programme, improved persistence
compared with once-weekly alendronate [47].
Adherence/persistence may also be enhanced
by simultaneously supporting the use of
non-pharmaceutical lifestyle modifications
and behavioural interventions [20].
These findings highlight the need for a
better understanding of non-persistent
patients and for the development of
initiatives to improve the quality of drug
therapy management [25,39]. Persistence
rates vary among antimuscarinics but
remain generally low in the UK and
elsewhere. Further studies are required to
investigate the reasons underlying this
trend, such as lack of efficacy, poor
tolerability or inconvenient dosing, why
patients are lost to follow-up, whether
symptoms resolve at some point during the
prescribed treatment, and whether lack of
patient understanding about the need for
long-term management is a factor.
ACKNOWLEDGEMENTS
This study was funded by Astellas Pharma
Europe, Ltd. Prescription data were provided
by CSD Ltd, Chertsey, UK. Writing and
editing assistance was provided by Tania
Kapoor and David Hallett of Darwin
Healthcare Communications, UK, and was
funded by Astellas.
CONFLICT OF INTEREST
Adrian Wagg is a speaker and researcher for
Astellas Pharma, Pfizer and Watson. Gerhard
©
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PERSISTENCE WITH ANTIMUSCARINIC THERAPY IN OAB
Compion, Amanda Fahey and Emad Siddiqui
are employees of Astella Pharma.
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Correspondence: Adrian Wagg, Divisional
Director, Geriatric Medicine, University of
Alberta, 300 Campus Tower, 8625 – 112
Street, Edmonton, AB, Canada T6G 1K8.
e-mail: [email protected]
Abbreviation: OAB, overactive bladder.
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