Rheumatol Int (2007) 27:743746

DOI 10.1007/s00296-006-0299-9
1 3
ORIGINAL ARTICLE
Factors aVecting drug treatment compliance in patients
with rheumatoid arthritis
Reyhan Tuncay Emel Eksioglu Banu Cakir
Eda Gurcay Aytul Cakci
Received: 12 September 2006 / Accepted: 16 December 2006 / Published online: 11 January 2007
Springer-Verlag 2007
Abstract We prospectively examined 100 rheuma-
toid arthritis (RA) patients to calculate drug compli-
ance rates, characteristics of compliant and non-
compliant patients, and changes in compliance over
time. Three assessments were obtained over a one-year
followup. Detailed drug history of RA and for con-
comitant disease was queried. Sedimentation rate, C-
reactive protein, and rheumatoid factor values, Ritchie
articular index, morning stiVness, and health assess-
ment questionnaire were evaluated. Twenty-six
patients (30.2%) were consistently compliant and 10
patients (11.6%) were consistently non-compliant.
Older age was associated with a greater likelihood of
compliance. Comparison of compliant and non-compli-
ant groups revealed no statistically signiWcant diVer-
ence in distribution of gender, disease duration, and
total number of pills taken for RA and/or total number
of pills taken for any reason. In conclusion, compliance
to drugs in RA patients is a common problem. Clinical
and laboratory activity of RA had less inXuence on
drug compliance. Older age is associated with a greater
likelihood of compliance.
Keywords Drug compliance Rheumatoid arthritis
Introduction
The main aim in rheumatoid arthritis (RA) therapy is
to reduce the symptoms and to inhibit joint deformities
and related functional loss. Success in RA therapy is
related to both drug eVectiveness and patient compli-
ance. Compliance has been deWned as extent to which
a persons behavior corresponds with recommenda-
tions from a health care provider [1].
A few studies have investigated the compliance to
drug treatment in RA. Considering that RA is a symp-
tomatic disease, patients are expected to be better
compliers than patients with rather asymptomatic con-
ditions, such as in hypertension and diabetes mellitus.
Reported rates for compliance to RA treatment have
been shown to range between 55.582% and 59.172%
for non-steroidal anti-inXammatory drugs (NSAID),
and disease-modifying anti-rheumatic drugs (DMARD),
respectively [2, 3].
In this study, we prospectively examined a total of
100 RA patients over a year to investigate their drug
compliance rates and to further examine the character-
istics of compliant and non-compliant patients, and the
changes in compliance over time.
Materials and methods
The study included 100 RA patients, consecutively
admitted to our Physical Therapy and Rehabilitation
Outpatient Clinic, between September 2002 and June
2003. Three assessments were completed over a one-
R. Tuncay E. Eksioglu (&) E. Gurcay A. Cakci
Department of Physical Therapy and Rehabilitation,
Ministry of Health, Ankara Diskapi Yildirim
Beyazit Education and Research Hospital,
57.sok 3/7 06510 Emek, Ankara, Turkey
e-mail: emeleksioglu@yahoo.com
B. Cakir
Department of Public Health,
Hacettepe University, Medical School,
Ankara, Turkey
744 Rheumatol Int (2007) 27:743746
1 3
year follow up: at baseline (T1) and 6 months apart
(T2 and T3). At each visit, the patients were inter-
viewed and examined by a physiatrist. Exclusion crite-
ria used were: grade 4 Steinbrocker classiWcations,
probable loss to follow-up, and not being under
DMARD therapy for the last 3 months. Standardized
data collection forms were used to collect information
on patients age, gender, disease duration (years), and
regularity of health insurance (regular, irregular). Of
note: all patients had social security insurance but
some had lapses in coverage. A detailed drug history
was obtained for both RA and concomitant disease (if
any). Blood tests were completed for sedimentation
rate, C-reactive protein (CRP), and rheumatoid factor
(RF) values. Disease activity was assessed using the
Ritchie articular index and morning stiVness (in min-
utes). The health assessment questionnaire (HAQ)
was used to evaluate functional activity. The treat-
ment regimen was recorded as NSAIDs, corticoster-
oids and DMARDs.
Compliance was evaluated at every visit, speciW-
cally for NSAIDs, corticosteroids, and DMARDs.
The patients were asked to respond regarding their
adherence to the prescribed dose and timing accord-
ing to a four-item scale: as, strictly, quite, not
really, or not at all. Patients were considered
compliant if they responded either strictly or
quite, regarding adherence to both the dose and the
timing of the prescribed medication. All other answers
were considered as non-compliance. Non-compli-
ance in any DMARDs among patients using combina-
tion therapy was also accepted as non-compliance. A
patient was considered as consistently compliant for
a given group of drugs (NSAIDs, DMARDs, corticos-
teroids), if she/he was compliant for both the dose and
timing of the prescribed medication over all the three
assessment visits.
Informed consent obtained from all of the patients
prior to the study and all procedures were in accor-
dance with the Helsinki Declarations of 1975.
Statistical analyses Analyses included frequency and
percent distributions. In comparative analysis of the
distribution of continuous variables, MannWhitney U
and KruskalWallis tests were used to compare and
contrast two and three groups, respectively. For cate-
gorical variables, diVerences between the groups were
analysed using Chi-square and Fishers exact tests, as
appropriate. Pearsons correlation coeYcients were
assessed to detect the relationship between continuous
variables. Level of statistical signiWcance was accepted
as 0.05 throughout the analyses. All analyses were con-
ducted using SPSS for Windows, version 11.0.
Results
At the end of 1 year, 86 of the 100 patients remained in
the cohort. All analyses were restricted to those 86
patients who remained in the study throughout the fol-
low-up period. 73 (84.9%) of the 86 patients were
female. Ages ranged between 25 and 74, with a mean
of 49.3 11.8 years. 78 (90.7%) patients had regular, 8
(9.7%) patients had irregular health insurance.
Reported disease duration ranged between 6 months
and 32 years, with an average of 9.2 7.1 years. When
the medication for concomitant diseases was consid-
ered, number of medications taken per day increased
up to 9.5 (min = 1, max = 22), on average. Half of the
patients (n = 43) were seropositive at the time of base-
line exam.
At baseline, all patients were under DMARD ther-
apy; 30 (34.8%), 62 (72.0%) and 53 patients (61.6%)
were using corticosteroids, NSAIDs, or combination
DMARD therapy at baseline, respectively. At the end
of the study, 26 patients (30.2%) were determined as
consistently compliant and 10 patients (11.6%) were
consistently non-compliant (Fig. 1). 36 patients
(41.8%) were consistently compliant with respect to
dose and 30 patients (34.8%) with respect to timing.
Characteristics of consistently complaint and non-com-
pliant patients are shown in Table 1.
Discussion
The success of the treatment of RA depends both on
the patient compliance and treatment eYcacy. A few
studies have examined compliance to drug treatment
among RA patients.
Compliance can be evaluated by assessing the dose
of various drugs and/or their metabolites in body Xuids,
but it is both an invasive and expensive method and
thus used infrequently [4]. Another compliance assess-
ment method is direct query of the patient regarding
whether or not she/he is taking the medicine as pre-
scribed [5].
In this study, 26 (30.2%) patients were consistently
compliant and 10 (11.6%) patients were consistently
non-compliant over the observation period of one year.
In a longitudinal study by Viller et al. [2] consistent
behaviour was recorded in 59.5% of RA cases; 35.7%
were consistently compliant and 23.8% consistently
non-compliant. In another study, in which 108 patients
with RA were interviewed, 39% were non-compliant to
the prescribed anti-rheumatic medication [6].
At baseline, self-reported non-compliance rate was
47.7% in our study cohort, and the percentage of
Rheumatol Int (2007) 27:743746 745
1 3
consistently compliant patients over one year was simi-
lar to that determined in the longitudinal study of Vil-
ler et al. [2].
Previous studies reported conXicting results on the
association between age and compliance results [2, 4].
Viller et al. [2] reported a positive correlation between
age and compliance and our results were conWrming
such a Wnding. Kauppi et al. [7] compared the self-
report functional capacity in patients with RA and
community controls, it was found that nonresponders
were younger. The present study showed no signiWcant
correlation between duration of disease and compliance
Fig. 1 General compliance
behaviour over one-year fol-
low up: T1, T2 and T3 corre-
spond to assessments at
baseline, 6th and 12th month
visits, respectively
+ -
+
+ Compliant
- Non-compliant
86
patients
36
80%
9
20%
26
72.2%
10
27.8%
3
33.3%
6
66.7%
45
52.3%
+
-
-
T1
T2
T3
41
47.7%
15
36.6%
18
69.2%
5
33.3%
10
66.7%
26
63.4%
30.2%
Consistently
compliant
11.6%
Consistently
non-compliant
-
8
30,3%
-
-
+
+
+
+
-
Table 1 Distribution
of patient characteristics
by compliance status
Characteristics Consistently
compliant
N = 26 (30.2%)
Consistently
noncompliant
N = 10 (11.6%)
P value
Gender 0.227
Male 3 (100.0%)
Female 23 (69.7%) 10 (30.3%)
Age (mean SD) (years) 52.42 10.18 37.80 9.34 0.003
Disease duration
(mean SD) (years)
9.40 7.56 6.20 4.13 0.380
Total number of pills
taken for RA (mean SD)
8 3.29 7.3 2.54 0.890
Total number of pills
taken (mean SD)
9.96 3.87 8.3 3.12 0.364
HAQ levels 0.85 0.67 0.63 0.47 0.610
Ritchie articular index 8.65 8.17 7.9 8.18 0.909
Morning stiVness 23.46 38.69 40 54.10 0.228
Sedimentation 35.38 22.89 26.60 15.71 0.618
CRP 21.12 6.09 9.53 8.23 0.629
Regularity of
health insurance
0.210
Regular 26 (78.7%) 7 (22.3%)
Irregular 3 (100%)
746 Rheumatol Int (2007) 27:743746
1 3
rates, as reported by Lee et al. [6] earlier. Previous
investigations have found that drug compliance was
inXuenced by the number of medications prescribed [8,
9]. In contrast, our Wndings suggested no signiWcant
association between compliance status and number of
medications used, or tablets taken per day. A similar
Wnding was also reported by Lee et al. [6] yet, the small
sample size of our cohort with consistent behaviour
regarding drug use might have hindered our detection
of such an association.
Problems with the health system environment and
Wnancial costs of medications are barriers to drug treat-
ment adherence in RA patients [8]. Yet, such an associ-
ation was not observed in our cohort. It is noteworthy;
on the other hand, that all our patients had some sort
of health insurance and had access to medical care
except occasional time gaps in coverage, due to late
payments for insurance and/or intermittent work
losses.
Our Wnding of a signiWcant association between dis-
ease activity and compliance in RA patients is in paral-
lel to that of Blackwell [9], suggesting disease activity
as the most important factor aVecting compliance.
Owen et al. [10] also indicated that patients with high
disease activity tend to be more compliant with treat-
ment than those with a low disease activity. Lee et al.
[6] on the other hand, reported that compared to
patients taking their medications regularly, non-com-
pliant patients had lower average joint counts and
lower average pain severity, indicating less severe
activity.
It is certain that physicians can better help their
patients with RA by improving their compliance with
the treatment. The reasons for compliance status are
manifold, and their identiWcation is important for tai-
loring appropriate treatment schemes for individual
patients.
Follow-up studies seem to be the best studies to
obtain valid epidemiological evidence with their ability
to study temporality, and to control for potential con-
founders. Our study is valuable for its longitudinal
design, yet, limited by its small sample size: it was very
expensive and labour-intense to follow 100 RA
patients for a year and it was hard to gather many RA
patients at regular time periods given that symptoms
per se avoided their access to medical care. Further
studies in larger cohorts and preferably with longer fol-
low-up periods would be quite beneWciary in determin-
ing personal, environmental, and/or disease-related
factors which reduce compliance rates. Once such fac-
tors are known, it would be easier to increase success
of the RA treatment. Finally, qualitative studies like
focus group discussions and in-depth interviews with
the patients would complement quantitative research
in this Weld.
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