Relationship between adherence to inhaled corticosteroids and poor outcomes among adults with asthma

Article (PDF Available)inJournal of Allergy and Clinical Immunology 114(6):1288-93 · February 2005with20 Reads
DOI: 10.1016/j.jaci.2004.09.028 · Source: PubMed
Abstract
Regular use of inhaled corticosteroids (ICSs) can improve asthma symptoms and prevent exacerbations. However, overall adherence is poor among patients with asthma. Objective To estimate the proportion of poor asthma-related outcomes attributable to ICS nonadherence. We retrospectively identified 405 adults age 18 to 50 years who had asthma and were members of a large health maintenance organization in southeast Michigan between January 1, 1999, and December 31, 2001. Adherence indices were calculated by using medical records and pharmacy claims. The main outcomes were the number of asthma-related outpatient visits, emergency department visits, and hospitalizations, as well as the frequency of oral steroid use. Overall adherence to ICS was approximately 50%. Adherence to ICS was significantly and negatively correlated with the number of emergency department visits (correlation coefficient [ R ] = -0.159), the number of fills of an oral steroid ( R = -0.179), and the total days' supply of oral steroid ( R = -0.154). After adjusting for potential confounders, including the prescribed amount of ICS, each 25% increase in the proportion of time without ICS medication resulted in a doubling of the rate of asthma-related hospitalization (relative rate, 2.01; 95% CI, 1.06-3.79). During the study period, there were 80 asthma-related hospitalizations; an estimated 32 hospitalizations would have occurred were there no gaps in medication use (60% reduction). Adherence to ICS is poor among adult patients with asthma and is correlated with several poor asthma-related outcomes. Less than perfect adherence to ICS appears to account for the majority of asthma-related hospitalizations.
Relationship between adherence to inhaled
corticosteroids and poor outcomes among
adults with asthma
L. Keoki Williams, MD, MPH,
a,b,c
Manel Pladevall, MD, MS,
b
Hugo Xi, MS,
b
Edward L. Peterson, PhD,
c
Christine Joseph, PhD,
c
Jennifer Elston Lafata, PhD,
b
Dennis R. Ownby, MD,
d
and Christine C. Johnson, PhD, MPH
b,c
Detroit,
Mich, and Augusta, Ga
Background: Regular use of inhaled corticosteroids (ICSs) can
improve asthma symptoms and prevent exacerbations.
However, overall adherence is poor among patients with
asthma.
Objective: To estimate the proportion of poor asthma-related
outcomes attributable to ICS nonadherence.
Methods: We retrospectively identified 405 adults age 18 to 50
years who had asthma and were members of a large health
maintenance organization in southeast Michigan between
January 1, 1999, and December 31, 2001. Adherence indices
were calculated by using medical records and pharmacy claims.
The main outcomes were the number of asthma-related
outpatient visits, emergency department visits, and
hospitalizations, as well as the frequency of oral steroid use.
Results: Overall adherence to ICS was approximately 50%.
Adherence to ICS was significantly and negatively correlated
with the number of emergency department visits (correlation
coefficient [R]=20.159), the number of fills of an oral steroid
(R = 20.179), and the total days’ supply of oral steroid
(R = 20.154). After adjusting for potential confounders,
including the prescribed amount of ICS, each 25% increase in
the proportion of time without ICS medication resulted in
a doubling of the rate of asthma-related hospitalization
(relative rate, 2.01; 95% CI, 1.06-3.79). During the study
period, there were 80 asthma-related hospitalizations; an
estimated 32 hospitalizations would have occurred were there
no gaps in medication use (60% reduction).
Conclusions: Adherence to ICS is poor among adult patients
with asthma and is correlated with several poor asthma-related
outcomes. Less than perfect adherence to ICS appears to
account for the majority of asthma-related hospitalizations.
(J Allergy Clin Immunol 2004;114:1288-93.)
Key words: Adherence, asthma, attributable risk, hospitalizations,
inhaled corticosteroids, emergency department visits
In 2001, an estimated 31.1 million adults in the United
States had a diagnosis of asthma.
1
Asthma is a leading
cause of preventable hospitalizations, and it accounts for
an estimated 14 million days of missed school and 100
million days of restricted activity yearly.
1
It has been
estimated that regular use of inhaled corticosteroids (ICSs)
could reduce asthma hospitalizations by as much as
80%,
2
and that the risk of death from asthma decreases
by 21% for each additional ICS canister used.
3
Despite
such potential, patients with asthma appear to adhere
poorly to prescribed ICS medications. For example,
Cochrane et al
4
found that patients with asthma took their
ICS as directed on only 20% to 73% of days. On 24% to
69% of days, patients took <50% of the prescribed dose.
Although routine use of ICS can markedly improve
symptoms and reduce asthma complications,
5-7
the con-
tribution of medication nonadherence to poor asthma
control has not been established. Therefore, the objective
of this study was to measure the association between
adherence to ICS and the frequency of asthma-related
outpatient visits, emergency department (ED) visits,
hospitalizations, and oral steroid use.
METHODS
This study was approved by the Institutional Review Board
and was in compliance with its Health Insurance Portability and
Accountability Act policy. Patients were all members of a large
health maintenance organization (HMO) in southeast Michigan, and
they received their care from a large, multispecialty medical group
consisting of approximately 800 physicians. Medical care claims data
From
a
the Department of Internal Medicine,
b
the Center for Health Services
Research, and
c
the Department of Biostatistics and Research Epidemiology,
Henry Ford Health System, Detroit; and
d
the Section of Allergy and
Immunology, Department of Pediatrics, Medical College of Georgia.
Supported in part by grants from the Fund for Henry Ford Hospital, the
National Institute of Allergy and Infectious Diseases (R01AI50681), and the
National Heart, Lung, and Blood Institute (R01HL068971).
Received for publication August 4, 2004; revised September 22, 2004;
accepted for publication September 24, 2004.
Reprint requests: L. Keoki Williams, MD, MPH, Center for Health Services
Research, 1 Ford Place, 3A CHSR, Detroit, MI 48202. E-mail: kwillia5@
hfhs.org.
0091-6749/$30.00
Ó 2004 American Academy of Allergy, Asthma and Immunology
doi:10.1016/j.jaci.2004.09.028
Abbreviations used
BHR: Bronchial hyperreactivity
CMA: Continuous, multiple-interval measure of
medication availability
CMG: Continuous, multiple-interval measure of
medication gaps
ED: Emergency department
HMO: Health maintenance organization
ICS: Inhaled corticosteroid
RR: Relative rate
1288
Asthma diagnosis and
treatment
were used retrospectively to identify individuals with asthma.
Individuals age 18 to 50 years with 1 or more of the following in
the index year (January 1, 1999, to December 31, 1999) were
considered to have asthma: (1) 1 or more hospitalizations with the
primary discharge diagnosis of asthma, (2) 1 or more ED visits with
the primary diagnosis of asthma, or (3) 4 or more outpatient visits
with asthma as a diagnosis. These criteria were adapted from claims-
based measures of asthma that have been reported elsewhere.
8-10
To
examine the relationship between medication adherence and out-
comes among adult patients with asthma, data had to be available
for the 2 years after the index year. Therefore, to be included in the
analyses, patients with asthma had to be continuously enrolled in the
HMO between January 1, 1999, and December 31, 2001; have both
medical and pharmacy benefit coverage during this time; and have
their care provided by physicians in the medical group. Patients were
excluded if they had a diagnosis of chronic obstructive pulmonary
disease or congestive heart failure at any outpatient visit, ED visit, or
hospitalization between January 1, 1999, and December 31, 2001.
The medical records of all individuals fulfilling these criteria
for asthma were abstracted for ICS use and dosage information.
Abstracted information was recorded and entered into an electronic
database by using TELEform (Cardiff Software, Vista, Calif) by
accredited medical record abstractors. These data were then linked
with prescription fill information from pharmacy claims data. The
number of days that a given fill of an ICS would last (ie, days
supplied) was calculated by dividing the canister size (ie, puffs per
canister) as derived from National Drug Codes in pharmacy claims
by the dosage information (ie, puffs per day) obtained in medical
records. The calculated days’ supply was used to estimate 2 measures
of adherence: (1) continuous, multiple-interval measure of medica-
tion availability (CMA), and (2) continuous, multiple-interval mea-
sure of medication gaps (CMG). The calculation of these indices is
discussed in detail by Steiner and Prochazka.
11
Briefly, CMA is
cumulative days’ supply/total number of days between refills during
the observation period, and CMG is total days of treatment gaps/total
number of days between refills during the observation period.
11
Although complementary, CMG indices assess the effect of lapses in
therapy (increases with increasing gaps or delays in refills), whereas
CMA indices assess the effect of cumulative drug dosage (increases
with increasing frequency of prescription fills).
11,12
These 2 indices
were calculated for each patient beginning with the first fill of an ICS
and ending with the last fill within the period of January 1, 2000,
through December 31, 2001. Therefore, ICS adherence could be
calculated only for individuals with at least 2 fills of an ICS in the
2-year observation period (n = 176). These calculations accounted
for changes in dosage and type of ICS. To ensure that gaps in ICS
refills were not a result of clinicians stopping medication, we also
abstracted provider notes for encounters in which an ICS was explicitly
stopped and another ICS was not started. Among patients for whom
adherence could be measured, we identified only 1 patient who had ICS
stopped while adherence was being measured and another ICS was not
started contemporaneously. Inclusion or exclusion of this patient did
not materially change the results; this individual was included in all
analyses.
Statistical analysis
Adherence indices were calculated as previously described.
Subjects for whom adherence could be calculated were compared
with individuals for whom adherence could not be calculated.
Differences in characteristics were assessed by using a x
2
test for
TABLE I. Characteristics of adults age 18 to 50 years with asthma by the availability of adherence information,
2000 to 2001
Characteristic Total (n = 405)
Patients with
adherence information (n = 176)
Patients without
adherence information (n = 229) P-value*
Age, y 6 SD 38.3 6 8.8 40.4 6 7.9 36.6 6 9.1 .001
Female (%) 270 (66.7) 119 (67.6) 151 (65.9) .751
Race .304
African American (%) 192 (47.4) 75 (42.6) 117 (51.1)
White (%) 200 (49.4) 94 (53.4) 106 (46.3)
Other (%) 13 (3.2) 7 (4.0) 6 (2.6)
Medication use in 2000-2001
1 ICS fill (%) 231 (57.0) 176 (100.0) 55 (24.0) .001
Mean ICS fills per person (6SD) 3.5 6 5.3 7.6 6 5.8 0.3 6 0.8 .001
1 inhaled b-agonist fill (%) 281 (69.4) 168 (95.5) 113 (49.3) .001
Mean inhaled b-agonist fills per
person (6SD)
7.4 6 9.6 13.5 6 10.8 2.6 6 4.7 .001
1 oral corticosteroid fill (%) 183 (45.2) 118 (67.1) 65 (28.4) .001
Mean oral corticosteroid fills
per person (6SD)
1.5 6 2.9 2.6 6 3.7 0.7 6 1.8 .001
Medical encounters in 2000-2001
1 ED visit for asthma (%) 101 (24.9) 49 (27.8) 52 (22.7) .248
Mean ED visits for asthma
per person (6SD)
0.5 6 1.2 0.6 6 1.5 0.4 6 1.1 .151
1 hospitalization for asthma (%) 38 (9.4) 23 (13.1) 15 (6.6) .038
Mean hospitalizations for asthma
per person (6SD)
0.2 6 0.8 0.3 6 1.1 0.1 6 0.4 .022
4 outpatient visits for asthma (%) 145 (35.8) 104 (59.1) 41 (17.9) .001
Mean outpatient visits for asthma
per person (6SD)
3.8 6 5.2 6.2 6 6.3 2.0 6 3.2 .001
*For the comparison of those with adherence information to those without such information.
Age on January 1, 1999.
J ALLERGY CLIN IMMUNOL
VOLUME 114, NUMBER 6
Williams et al 1289
Asthma diagnosis and
treatment
categorical variables and a nonparametric Mann-Whitney 2-sample
test for continuous variables.
The primary outcome measures were the number of asthma-
related outpatient visits, asthma-related ED visits, asthma-related
hospitalizations, and oral steroid uses during the period of January 1,
2000, through December 31, 2001. The outcome measures were
related to CMA and CMG by using a Spearman correlation
coefficient. Poisson regression methodology was then used to assess
the relationship between adherence indices and the frequency of
asthma-related outcomes.
13
A univariable model was fit, followed by
2 multivariable models. Multivariable models adjusted for potential
confounders including potential markers of disease severity, such as
the number of b-agonist fills,
8
the number of ICS fills, and the
prescribed number of ICS fills. The first multivariable model (model
1) adjusted for sex, race, age, number of b-agonist fills, and number of
ICS fills (log-transformed). The second multivariable model (model
2) replaced the number of ICS fills with prescribed number of ICS
fills. This last variable was computed as the number of ICS fills di-
vided by CMA (log-transformed). The model was fit with a correc-
tion for overdispersion. A relative rate (RR) was estimated in each
model for a 0.25 change in either CMA or CMG.
We adapted the methodology of Greenland and Drescher
14
to
calculate the proportion of hospitalizations attributable to non-
adherence. The coefficient estimates from the multivariable
Poisson model (model 2) were used to derive an asthma-related
hospitalization rate for each individual with adherence information
(n = 176) under conditions of perfect ICS adherence (ie, CMG set to
0). This approach allowed us to account for other individual risk
factors that could contribute to the rate of hospitalization. The
expected number of asthma-related hospitalizations among persons
with adherence information was therefore the sum of these individual
rates. The number of asthma-related hospitalizations attributable to
nonadherence was then calculated by subtracting the expected
number of asthma-related hospitalizations from the observed number
of hospitalizations among patients with adherence information.
The proportion of all asthma-related hospitalizations attributable to
nonadherence was estimated by dividing this difference by the total
number of asthma-related hospitalizations observed among the 405
adults studied (ie, persons with and without adherence information).
This calculation assumes that the only hospitalizations that could
have been prevented by improved adherence were among the 176
subjects for whom adherence was measured. The asthma-related
hospitalizations that occurred in the 229 (56%) patients without
adherence information were considered immutable and therefore
contributed only to the calculation of the denominator, the total
asthma-related hospitalizations, but not to the numerator, the number
of asthma-related hospitalizations preventable by improved adher-
ence. Statistical analyses were performed by using SAS v8.0 (SAS
Institute, Cary, NC).
15
RESULTS
In the year 1999, 2150 patients between the ages of 18
and 50 years met the study criteria for having asthma. Of
these adult patients with asthma, 461 were continuously
enrolled in the HMO; had both medical and pharmacy
benefits; and had their care provided by a group physi-
cian between January 1, 1999, and December 31, 2001.
Another 56 patients were excluded because they had
a diagnosis of chronic obstructive pulmonary disease or
congestive heart failure. The characteristics of the remain-
ing 405 patients are shown in Table I. Approximately
equal numbers were African American (n = 192) and
white (n = 200). Two-hundred thirty-one (57.0%) patients
had at least 1 ICS fill in either 2000 or 2001, whereas 281
(69.4%) had at least 1 prescription fill of an inhaled
b-agonist. The adherence measures, CMA and CMG,
could be calculated for 176 patients (ie, patients who had
at least 2 fills of an ICS in the years 2000 and 2001). Not
surprisingly, those for whom adherence could be mea-
sured had greater numbers of ICS fills compared with
those for whom adherence could not be measured. The
former also had other indicators of more severe asthma,
such as greater use of b-agonist inhalers, greater use of
oral corticosteroids, and more frequent asthma-related
hospitalizations. The mean CMA and CMG for ICS were
0.50 (SD, 60.37) and 0.54 (SD, 60.27), respectively. In
other words, overall adherence to ICS, as estimated by
CMA or 1-CMG, was approximately 50%.
As expected, CMA, a measure that increases when
patients fill their ICS prescriptions on time, was negatively
associated with poor asthma outcomes (Table II). Sim-
ilarly, CMG, which increases with increasing lapses or
delays in filling prescriptions, was positively associated
with poor asthma outcomes. Both CMA and CMG were
significantly correlated with the number of asthma-related
ED visits and the frequency of oral steroid use (both total
number of prescriptions filled and total number of days
treated). The weakest associations were seen for the
frequency of outpatient asthma visits, which did not
appear to be correlated with level of adherence. Slightly
stronger correlations were seen between adherence and
asthma outcomes when using CMG compared with CMA.
Because the relationships seen between adherence
indices and asthma outcomes could be reflective of
total ICS use rather than adherence alone, we simulta-
neously adjusted for inhaled steroid use, age, sex, race,
and b-agonist in the regression models ( Table III). In
TABLE II. Correlation between measures of adherence
to ICSs and asthma-related outcomes in adult patients
with asthma, 2000 to 2001
Variable 1 Variable 2 Correlation
CMA Asthma-related outpatient visits 20.015
Asthma-related ED visits 20.159*
Asthma-related hospitalizations 20.130
Fills of oral steroids 20.179*
Days of oral steroids 20.154*
CMG Asthma-related outpatient visits 0.030
Asthma-related ED visits 0.171*
Asthma-related hospitalizations 0.147
Fills of oral steroids 0.190*
Days of oral steroids 0.164*
CMA denotes continuous, multiple interval of medication availability
which is equal to the cumulative days’ supply of inhaled steroids divided
by the total number of days between refills for the period January 1, 2000
through December 31, 2001.
CMG denotes continuous, multiple-interval measures of medication gaps
which, on the basis of days’ supply of inhaled steroids, is equal to the total
number of days of without an inhaled steroid divided by the total days
between refills for the period January 1, 2000 through December 31, 2001.
*P<.05.
J ALLERGY CLIN IMMUNOL
DECEMBER 2004
1290 Williams et al
Asthma diagnosis and
treatment
model 1, we adjusted for the total number of ICS fills made
by individual patients in 2000 and 2001. Because the pre-
scribed ICS dose may be a proxy for disease severity, in
model 2, we adjusted by the total number of ICS fills that
an individual should have had in 2000 and 2001 (ie, total
number of ICS fills divided by CMA). As shown pre-
viously, nonadherence as measured by increasing CMG
was positively, albeit not always significantly, associated
with the rate of asthma-related ED visits, asthma-related
hospitalizations, and oral steroid use in both the un-
adjusted and adjusted regression analyses. In the un-
adjusted model and in model 2, CMG was significantly
associated with the rate of asthma-related hospitalizations.
Each 25% increase in the proportion of time without ICS
medication resulted in a doubling of the rate of asthma-
related hospitalization (model 2, RR, 2.01; 95% CI, 1.06-
3.79). CMG was also significantly associated with the rate
of fills of an oral steroid (model 1, RR, 1.49; 95% CI, 1.10-
2.02). Simultaneously adjusting models 1 and 2 for other
potential markers of disease severity, such as oral steroid
use and asthma-related hospitalizations, in 1999 did not
substantively change our results (data not shown). CMA
was similarly significantly associated with the rate of fills
of an oral steroid (model 1, RR, 0.75; 95% CI, 0.58-0.97),
meaning that each 25% increase in adherence to ICS as
measured by CMA was associated in a 25% reduction in
the rate of oral steroid fills (data not shown).
Between 2000 and 2001, there were 80 asthma-related
hospitalizations among the 405 adults with asthma. Fifty-
eight of asthma-related hospitalizations occurred among
the 179 patients for whom adherence could be measured,
and 22 hospitalizations occurred in those without adher-
ence information. Among those for whom adherence could
be measured, we estimate that the number of hospitaliza-
tions would have been reduced to 10.0 (82.8% reduction)
were there no lapses in medication use (ie, CMG = 0). In
other words, 60.0% of all asthma-related hospitalizations
could be attributed to less than perfect adherence to ICS.
DISCUSSION
A previous study by Donahue et al
8
found that patients
with asthma who filled a prescription for an ICS were 50%
less likely to be hospitalized for asthma compared with
patients who did not receive an inhaled steroid (relative
risk, 0.5; 95% CI, 0.4-0.6). However, the investigators did
not examine whether patients took their ICS as directed.
We find that apart from the total number of ICS fills, gaps
or lapses in adherence are an independent predictor of
asthma-related hospitalizations. In fact, we estimate that
60% of all asthma-related hospitalizations in our study
population could be attributed to less than perfect
adherence to ICSs.
These findings comport with trials showing that
cessation of ICSs can result in rapid declines in FEV
1
,
morning and evening peak expiratory flow, and quality
of life, as well as increases in bronchial reactivity, daily
asthma symptom scores, sputum eosinophils, and levels of
exhaled nitric oxide.
16,17
For example, Haahtela et al
16
showed that average FEV
1
and bronchial hyper-reactivity
(BHR) to methacholine did not change significantly in
individuals switched from budesonide at 1200 mg per day
to 400 mg per day, whereas switching to placebo resulted
in a significant drop in FEV
1
and a rise in BHR. Vathenen
et al
18
found that after 6 weeks of therapy with budeso-
nide, BHR returned to baseline within a week of
discontinuing treatment.
Although several studies have shown that overall
patient adherence to ICS is poor,
4,19-21
few have examined
the relationship between adherence and asthma outcomes.
In a small study by Milgrom et al,
20
adherence to ICS was
measured by using electronically monitored metered-dose
inhalers in 24 asthmatic children age 8 to 12 years. During
this 13-week study, children who required a burst dose of
oral corticosteroids had a median ICS adherence value of
13.7%, compared with a median ICS adherence of 68.2%
in children not requiring oral steroids (P = .008). In the
current study, we have also found a significant correlation
between the need for oral steroids and adherence to ICS.
We did not, however, find a significant relationship be-
tween adherence and outpatient visits for asthma, which is
not surprising, because the latter may not reflect poor
asthma control.
22
This study must be interpreted in light of its limitations.
First, the study population examined here consisted
of individuals with both medical and pharmaceutical
coverage. On the basis of studies showing a positive
TABLE III. Unadjusted and adjusted association between adherence and asthma-related outcomes in adults
age 18 to 50 years, 2000 to 2001
Per 25% increase in CMG
Outcome Unadjusted RR (95% CI) Model 1* RR (95% CI) Model 2y RR (95% CI)
Outpatient visit 1.07 (0.93-1.23) 1.13 (0.97-1.30) 0.96 (0.83-1.11)
Asthma-related ED visit 1.36 (0.97-1.92) 1.27 (0.85-1.77) 1.25 (0.84-1.85)
Asthma-related hospitalization 1.80 (1.04-3.14)à 1.27 (0.75-2.14) 2.01 (1.06-3.79)à
Fills of oral steroids 1.22 (0.99-1.50) 1.49 (1.10-2.02)à 1.26 (0.95-1.67)
Days of oral steroids 1.18 (0.88-1.59) 1.53 (1.00-2.36) 1.27 (0.85-1.88)
*Adjusted for sex, race, age, number of b-agonist fills from 2000 to 2001, and number of ICS fills from 2000 to 2001.
Adjusted for sex, race, age, number of b-agonist fills from 2000 to 2001, and prescribed number of ICS fills from 2000 to 2001 (ie, total number of ICS fills
divided by CMA).
àP<.05.
J ALLERGY CLIN IMMUNOL
VOLUME 114, NUMBER 6
Williams et al 1291
Asthma diagnosis and
treatment
relationship between both commercial insurance posses-
sion and household income and adherence,
19,23
our esti-
mates of overall adherence are likely to be greater than
those of the general population. Similarly, our measure-
ment of adherence was limited to persons with 2 or more
fills of an ICS during the study period, and therefore, these
estimates did not account for individuals who never filled
their ICS prescription or filled it only once. Watts et al
24
performed a study of primary nonadherence (ie, the
nonfilling of prescriptions) in Port Lincoln, South
Australia. Of the 359 asthma medication prescriptions
written, 108 (30%) were never filled in 6 months of
follow-up. Together, these data suggest that the proportion
of poor asthma outcomes attributable to nonadherence
may be greater than reported here. When estimating the
proportion of hospitalizations attributable to nonadher-
ence, we adjusted for other risk factors that could have
contributed to the rate of hospitalization. However, it is
also possible that persons who were nonadherent differed
from persons who were adherent in other unmeasured
ways, which could have accounted for some of the
difference in these rates. This may have resulted in an
overestimation of the proportion of hospitalizations
attributable to nonadherence. Before generalizing these
results, it is also important to note that our definition of
asthma may have identified patients with more severe
asthma who were more likely to benefit from continuous
ICS use. Because pharmacy claims data were used to
measure adherence, we could not assess daily patterns of
ICS use. Therefore, although CMG, a measure of gaps in
ICS refills, was the better predictor of poor asthma
outcomes, we could not distinguish protracted period off
therapy from chronic or intermittent underdosing. This
prevented us from being able to correlate specific patterns
and timing of use with adverse asthma outcomes. Last,
depending on the statistical method used, nonadherence
to ICS was significantly associated with different poor
asthma outcomes. However, the consistency of these asso-
ciations in both magnitude and direction across outcomes
suggests that statistical differences were a result of limited
power rather than a true lack of association. Despite this
limitation, nonadherence was still significantly associated
with oral steroid use and asthma-related hospitalizations
after adjusting for multiple potential confounders.
Although this study demonstrates the important re-
lationship between ICS adherence and asthma-related
outcomes, improving both is likely to be difficult. Bender
et al
25
recently reviewed interventions to improve adher-
ence among patients with asthma. The authors found
that few behavioral or educational interventions were
very effective at improving adherence and asthma control,
despite considerable time investment in some cases.
Similar disappointing results have been seen for adherence
interventions in other disease conditions.
26
However, recent data suggest that adherence can be
improved when patients know that adherence is being
measured and this information is regularly discussed with
them. Onyirimba et al
27
measured adherence to ICS by
using electronically monitored metered-dose inhalers in
19 patients with asthma over a 10-week period. Patients
who received regular adherence feedback from their
clinician had sustained levels of adherence >70% com-
pared with those in the control group whose adherence rate
fell below 30% by week 10. In a study by Reddel et al,
28
patients’overalladherence to peak expiratory flowmeasure-
ment was 89% over a period of 72 weeks when participants
were aware that peak expiratory flow meter use was being
electronically recorded and these results were discussed
with them regularly.
Our finding that ICS adherence, as measured by using
both medical records and pharmacy claims data, is associ-
ated with important asthma outcomes suggests that these
measures may be clinically useful. However, although
medical records and pharmacy claims data are ubiquitous,
patient adherence information is not, and to date, there are
few studies looking at its introduction in clinical prac-
tice.
29,30
Developing a mechanism to feed back adherence
information routinely to both clinicians and patients may
result in improved adherence and better asthma control.
Our demonstration that ICS adherence can be estimated by
using prescription refill information, and that these
measures are independently associated with important
asthma outcomes, is a first step in that direction.
We thank Lula Adams for her coordination of this project, as well
as Cheryl Spoutz, Rita Montague, and all of the medical record
abstractors whose help and hard work made this study possible.
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    • "Nearly 60% of patients with persistent asthma have suboptimal asthma control, a figure that has remained unchanged since 2000 in Canada and abroad123. Suboptimal asthma control is associated with preventable asthma symptoms, overuse of bronchodilators (i.e., rescue medication), functional impairment (e.g., work absenteeism), increased health service use (e.g., emergency visits), and even death [4,5]. The goal of asthma management is to control the disease so that patients may lead a normal active life and prevent long-term impairment. "
    [Show abstract] [Hide abstract] ABSTRACT: Although asthma morbidity can be prevented through long-term controller medication, most patients with persistent asthma do not take their daily inhaled corticosteroid. The objective of this study was to gather patients' insights into barriers and facilitators to taking long-term daily inhaled corticosteroids as basis for future knowledge translation interventions. We conducted a collective qualitative case study. We interviewed 24 adults, adolescents, or parents of children, with asthma who had received a prescription of long-term inhaled corticosteroids in the previous year. The one-hour face-to-face interviews revolved around patients' perceptions of asthma, use of asthma medications, current self-management, prior changes in self-management, as well as patient-physician relationship. We sought barriers and facilitators to optimal asthma management. Interviews were transcribed verbatim and transcripts were analyzed using a thematic approach. Patients were aged 2-76 years old and 58% were female. Nine patients were followed by an asthma specialist (pulmonologist or allergist), 13 patients by family doctors or pediatricians, and two patients had no regular follow-up. Barriers and facilitators to long-term daily inhaled corticosteroids were classified into the following loci of responsibility and its corresponding domains: (1) patient (cognition; motivation, attitudes and preferences; practical implementation; and parental support); (2) patient-physician interaction (communication and patient-physician relationship); and (3) health care system (resources and services). Patients recognized that several barriers and facilitators fell within their own responsibility. They also underlined the crucial impact (positive or negative) on their adherence of the quality of patient-physician interaction and health care system accessibility. We identified a close relationship between reported barriers and facilitators to adherence to long-term daily controller medication for asthma within three loci of responsibility. As such, patients' adherence must be approached as a multi-level phenomenon; moreover, interventions targeting the patient, the patient-physician interaction, and the health care system are recommended. The present study offers a potential taxonomy of barriers and facilitators to adherence to long-term daily inhaled corticosteroids therapy that, once validated, may be used for planning a knowledge translation intervention and may be applicable to other chronic conditions.
    Full-text · Article · Apr 2015
    • "Adherence to asthma medication is an important consideration during treatment as it is low irrespective of patient age [16, 17, 18], decreases further amongst those patients who present with difficult-to-control asthma [17, 19] , and is correlated with negative out- comes [17, 18, 20]. Following the approval and introduction of the budesonide/formoterol MRT in Europe, this observational study was undertaken to fulfil regulatory commitments and examine this new treatment regimen in real-life clinical practice. "
    [Show abstract] [Hide abstract] ABSTRACT: The efficacy and safety of budesonide/formoterol maintenance and reliever therapy (MRT) has been demonstrated in phase III clinical studies, but limited data are available in a real-life setting. We examined the pattern of maintenance and as-needed inhaler use in routine clinical practice among patients with asthma receiving budesonide/formoterol MRT (NCT00505388). This 12-month European observational study enrolled patients prescribed budesonide/formoterol MRT and grouped them based on regimen: 80/4.5 μg one inhalation twice daily (b.i.d.); 160/4.5 μg one inhalation b.i.d.; 160/4.5 μg two inhalations b.i.d. (all plus as needed). Patient data were collected daily using an interactive voice- or web-response system. The primary outcome measure was total number of budesonide/formoterol inhalations/day. Overall, 4,581 patients were included (64% female; mean age 48.4 years; regimen: 80/4.5 μg, n = 119; 160/4.5 μg, n = 3,106; 2 × 160/4.5 μg, n = 1,355). Mean (median) total numbers of budesonide/formoterol inhalations/day were 2.48 (2.11), 2.53 (2.14), and 4.27 (4.05) for 80/4.5 μg b.i.d., 160/4.5 μg b.i.d., and 2 × 160/4.5 μg b.i.d., respectively; corresponding mean (median) number of as-needed inhalations/day were 0.68 (0.17), 0.73 (0.26), and 1.08 (0.45), respectively. As-needed budesonide/formoterol use was generally low with a mean of 61 - 66% of reliever-free days; over 4 reliever inhalations/day occurred on a mean of 0.4 - 2.5% of days for all budesonide/formoterol MRT regimens. Inroutine clinical practice, all budesonide/formoterol MRT regimens were associated with a high proportion of reliever-free days and low incidence of high reliever-use days, indicating acceptable levels of asthma control with this symptom-adjusted controller regimen.
    Full-text · Article · Apr 2015
    • "Yet despite recommendations, there is a disappointingly low level of adherence to asthma controller therapies [9]. The average rate of adherence to inhaled corticosteroids for asthma is reported to be between 22 and 63%10111213141516. Medication regimens for asthma are particularly vulnerable to adherence problems because of the requirement for long-term use and the long periods of symptom remission experienced by patients [17]. "
    [Show abstract] [Hide abstract] ABSTRACT: Medication regimens for asthma are particularly vulnerable to adherence problems because of the requirement for long-term use and periods of symptom remission experienced by patients. Pharmacists are suited to impact medication adherence given their training, skills, and frequent contact with patients. The Empowering pharmacists in asthma management through interactive SMS (EmPhAsIS) trial involves an intervention leveraging mobile health (mHealth) technology to support community pharmacy practice with the hypothesis of improved medication adherence in asthma. This study is a pragmatic pharmacy-based, cluster, randomized controlled trial with 12 months of intervention delivery and follow-up. Pharmacies (the clusters) will be randomized at a 1:1 ratio to provide intervention or usual care. The EmPhAsIS intervention consists of patient asthma education, short message service (SMS)-based monthly assessment of adherence, and follow-up of non-adherent individuals by community pharmacists. There are no inclusion or exclusion criteria for pharmacies. Patients are eligible if they: are 14 years of age or older, fill a prescription for inhaled corticosteroid (either monotherapy or in a combination inhaler with long-acting beta-agonists), have been diagnosed with asthma, possess a mobile phone with SMS capabilities, and have no communication difficulties such as inability to communicate in English, or significant impairment in vision, hearing, or speech. The primary outcome is adherence to inhaled corticosteroids ascertained by the medication possession ratio, the ratio of the days of medication supplied to days in a given time interval. This study will also evaluate secondary outcomes including: asthma control, asthma-related quality of life, asthma-related hospital admissions, and use of reliever medications during the follow-up period. A nested economic evaluation using a probabilistic decision-analytic model will be used to perform a cost-effectiveness analysis from the societal perspective of the intervention compared with usual care over a 10-year time horizon. Considering the prevalence of asthma, the extent of the non-adherence problem in this disease, and the availability of effective treatments, there is a tremendous potential to reduce the burden of asthma through improving adherence. This is the first study of an intervention based on mobile communication technology involving community pharmacists in asthma management.Trial registration: ClinicalTrials.gov identifier: NCT 02170883; date of registration: 19 June 2014.
    Full-text · Article · Dec 2014
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