Supplements New Perspectives on Overactive Bladder: Quality of Life Impact, Medication Persistency, and Treatmen
Persistence With Overactive Bladder Pharmacotherapy in a Medicaid Population
To determine whether differences in persistence
by drug are statistically significant
after adjusting for age, sex, and race, a time-dependent
Cox model was constructed that
allowed different HRs before and after the
critical 30-day mark. Using the Cox model
without controlling for covariates, and only
the time variable, results showed that oxybutynin
IR had a significantly higher rate of
discontinuation than tolterodine ER within
the first 30 days (HR = 1.25; 95% confidence
interval [CI], 1.01-1.53). After this initially
poorer start, oxybutynin IR users discontinue
at statistically the same rate as tolterodine
ER users. This corresponds to the
unadjusted survival curve.
In a Cox model adjusting for age (<18
years, 18-40 years, >40 years), sex, and race
(Caucasian, African American, other), oxybutynin
IR is not significantly different
from tolterodine ER (HR = 1.09; 95% CI,
0.88-1.35) in the initial 30-day period
(Table 2). Table 2 shows the HRs of non-persistence of oxybutynin IR and oxybutynin
ER compared with tolterodine ER.
Because of the large drop in persistence for
any of the 3 drugs in the first 30 days, the
analysis is stratified by time period, differentiating
between trends in the first 30 days
and trends in the period after 30 days. The
effects are also shown on nonpersistence of
age, sex, and race. In the first 30 days, the
oxybutynin ER and tolterodine ER do not
differ statistically, in both adjusted (HR =
0.96; 95% CI, 0.60-1.53) and unadjusted
models (HR = 1.04; 95% CI, 0.80-1.35).
However, of the users who continue past 30
days, oxybutynin ER has a higher risk of discontinuation
in both the adjusted (HR =
1.47; 95% CI, 1.01-2.14) and unadjusted
models (HR = 1.50; 95% CI, 1.03-2.18).
Possession Time. The survival curves for
patient possession time with an MPR >30%
are shown by index drug in Figure 2. About
45% of those starting on oxybutynin IR and
55% of those starting on either tolterodine
ER or oxybutynin ER maintain possession
after 30 days. At 1 year, 16%, 22%, and 15%
are maintaining possession of oxybutynin
IR, tolterodine ER, and oxybutynin ER,
respectively. The shape of the possessiontime
survival curve points to a time-dependent
model that can handle different HRs
before and after 30 days of possession time.
No drug shows significantly different hazard
risk than another in either time period,
in both unadjusted and adjusted Cox models.
Detailed HR results are included in
In a comparison of the distributions for
persistence and possession time, it was
found that possession time is just 30 days
longer than persistence for 80% of patients.
On average, tolterodine ER and oxybutynin
ER users possess medication approximately
40 days longer than they persist. The mean
difference is greater for oxybutynin IR users,
which is approximately 60 days.
Switching. About 6% of the cohort
switched drugs before they were determined
to be otherwise nonpersistent or reached the
end of the enrollment period, with little difference
by index drug. Of those who did
switch, 44%, 56%, and 20% (tolterodine ER,
oxybutynin ER, and oxybutynin IR, respectively)
switched in the first 30 days. The corresponding
rates by 120 days were 50%, 80%,
Demographic and Clinical Predictors.
Table 2 includes HRs from the Cox multivariate
model, indicating how age, race, and
sex affect persistence and possession time.
Younger patients are half as likely to discontinue
their original therapy compared with
young adults aged 18 to 39 years (HR = 1.56;
95% CI, 1.33-1.82). Patients aged 40 to 64
years are significantly less likely to discontinue
therapy than the younger adults (HR =
0.85; 95% CI, 0.74-0.97). Age has a similar
effect on possession time.
African Americans and other minorities
were more likely than Caucasians to discontinue
or switch (HR = 1.22; 95% CI, 1.09-
1.36). At 90 days, only 15% of African
Americans remain persistent compared with
27% of Caucasians. Similar racial effects
held for possession time. Sex did not affect
long-term persistence; however, an interesting
difference shows up in the first 30 days.
If men were going to discontinue, they were
more likely than women to stop therapy in
the first 30 days (HR = 1.16; 95% CI, 1.01-1.34). Men who continue past 30 days are
less likely than women to stop (HR = 0.74;
95% CI, 0.56-0.94).
As might be expected, patients who had a
qualified diagnosis for OAB in the 6 months
before initiating medication were less likely
to discontinue than others (HR = 0.80; 95%
CI, 0.72-0.89; n = 715).
Because patients eligible for Medicare
were excluded and there is a high prevalence
of children in most Medicaid plans, the
cohort of OAB patients identified here was
younger than what might be expected in
terms of more typical OAB patients. Among
the 3 products of interest, oxybutynin IR use
is predominant at 76% of users. This is likely
a result of the preferred use of generic
drugs as a cost-containment measure in
many Medicaid plans.
Rates of persistence with OAB drugs were
found to be low among these Medicaid MCO
patients, with only 32% of the oxybutynin IR
users and 44% of users of either once-daily
agent refilling their first prescription at 30
days. The difference is associated with the
greater number of young adults in the oxybutynin
IR cohort, whose persistence is significantly
less than older adults. Of those
patients who did fill a second prescription,
persistence was significantly better for
patients receiving tolterodine ER compared
with oxybutynin ER; the significant difference
persists after adjusting for demographic
variables (HR = 1.47; 95% CI, 1.01-2.14).
In 2 clinical trials comparing the 2 longeracting
agents over a 12-week period, results
on relative efficacy were mixed, whereas
fewer tolterodine ER users experienced dry
mouth than did oxybutynin ER users.17,18
Thus, this difference may be a result of fewer
patients experiencing adverse effects, such
as dry mouth; however, a specific study that
tests this hypothesis would be needed for
After the initially poorer persistence for
oxybutynin IR users, those who do continue
after 30 days adhere at about the same rate
as tolterodine ER users. It is possible that
these patients experience more side effects
at the initiation of therapy. However, those
who do not experience these side effects are
able to persist without problems later. There
was less difference between index drugs, and
possession time lasted 1 to 2 months longer
than persistence on a mean basis. Like persistence,
possession time was lower among
younger or minority individuals.
Little data on persistence with OAB medication
has been published in peer-reviewed
journals, but research abstracts of other
claims studies also report low rates of persistence.
For immediate-release formulations,
Juzba and colleagues19 found that nearly half
(48.2%) of the patients in their 1999 claims
study failed to refill their first prescription,
and that continuation was more likely for
patients taking tolterodine ER than oxybutynin
IR (n = 436). Boccuzzi et al found 12-month persistence rates of 24% for
tolterodine ER patients, and 17% for oxybutynin
IR patients (n = 36 142).12 Chui et al9
and Yu et al10 reported similar 12-month
results also from studies of claims data. Zhou
et al reported an adjusted odds ratio of discontinuation
for tolterodine ER versus oxybutynin
IR users as 0.66 (P <.001; n =
Poor compliance can be attributed to a
variety of factors, including low levels of formal
education, cultural factors, side effects,
and financial barriers.15,16,20 Clinical studies
and patient surveys are necessary to better
understand reasons for nonpersistence with
OAB medications and to develop interventions
to improve persistence. Clinical trials
of transdermal patches for administration of
oxybutynin ER have indicated reduced incidence
of side effects, and studies of these
new therapies in routine clinical practice are
needed to replicate these findings in the real
A good patient education program favorably
impacts patient behavior, including compliance
with short-term therapies, long-term
management of chronic conditions, and preventive
lifestyle recommendations.23 It can
also build trust between healthcare providers
and reduce anxiety, thus favorably impacting
health outcome and patient satisfaction.24
Patient education programs have been carried
out in various settings and proved to be successful
in improving patient compliance.25-27
Because of its chronic nature, unpleasant side
effects, and chronic treatment, a behavior-modifying
education program would be of
essential value to patients with OAB, particularly
among those with lower educational status.
Further efforts are called for to design an
effective educational program specifically targeted
to this population.
There are limitations to assessing persistence
patterns from claims data, as done in
this study. Different methods are used to
measure persistency in patient populations.
The most commonly used method involves
obtaining information on pharmacy refill
records, often from third-party institutions.
These records are beneficial as an economical
method for tracking compliance on
large numbers of patients. However, they
may overestimate compliance in that they
represent prescriptions filled or refilled and
not medications actually taken.
It can be concluded that persistence with
OAB therapy in a Medicaid MCO population
is low. Research is needed to understand the
reasons for low persistence, so that interventions
can be developed to improve persistence
and compliance. Medicaid managed
care plans will continue to face demands for
reduced budgets and will continue to
explore different approaches to optimize
care and reduce risk. If low persistence with
OAB therapies increases total cost of care
for patients with OAB, it is critical that managed
Medicaid plans understand and address
this problem. Further studies are needed to
understand OAB drug treatment compliance
patterns in these populations as well as the
factors influencing these patterns.
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