Health-related quality of life in patients with rheumatoid arthritis and in patients with ankylosing spondylitis.
ABSTRACT In this review the influence of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) on a wide range of health-related quality of life (HRQoL) domains will be described. The domains most frequently studied are pain, functional disability, fatigue and mental problems. In addition, age and socio-economic aspects such as employment and economic status as well as education affect patient-reported HRQoL.Although many studies have assessed the impact on HRQoL of a single disease state, either RA or AS, few studies have focused on a direct comparison between those both diagnostic groups. In general, patients with RA and AS report significant decrements in HRQoL in comparison with the general population. It has been shown that the magnitude of the impairment is similar among both patients group.
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ABSTRACT: OBJECTIVE.: To describe the long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). METHODS.: Longitudinal data over a period of eleven years were collected from 882 patients with RA at study inclusion. Patient-reported outcomes were collected in 1997, 1998, 1999, 2002 and 2008. Physical functioning was measured with the Health Assessment Questionnaire and the Physical Component Scale of the Short Form-36 Health Survey. Somatic comorbidity was measured by a questionnaire including 13 chronic diseases. Comorbid depression was measured with the Center for Epidemiologic Depression Scale. We distinguished four groups of patients based on comorbidity at baseline. RESULTS.: 78% of the patients at baseline were women. The mean age was 59.3 (SD 14.8) years and the median disease duration was 5.0 (IQR 2.0-14.0) years. For the total group of patients with RA physical functioning improved over time. Patients with somatic comorbidity, comorbid depression or both, demonstrated worse physical functioning than patients without comorbidity, at all data collection points. Both groups with comorbid depression had the lowest scores. Only patients with both somatic comorbidity and comorbid depression showed significantly less improvement in physical functioning over time. CONCLUSION.: Both somatic comorbidity and comorbid depression were negatively associated with physical functioning during an eleven-year follow-up period. Furthermore, their combination seems to be especially detrimental to physical functioning over time. These results emphasize the need to take somatic comorbidity and comorbid depression into account in the screening and treatment of patients with RA. © 2013 by the American College of Rheumatology.Arthritis care & research. 01/2013;
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ABSTRACT: Fatigue is a frequent symptom during ankylosing spondylitis (AS) often under estimated which needs to be measured properly with respect to its intensity by appropriate measures, such as the multidimensional assessment of fatigue (MAF). The aims of this study were to translate into the classic Arabic version of the MAF questionnaire and to validate its use for assessing fatigue in Moroccan patients with AS. The MAF contains 16 items with a global fatigue index (IGF). The MAF was translated and back-translated to arabic, pretested and reviewed by a committee following the Guillemin criteria (J Clin Epidemiol 46:1417-1432, 1993). It was then validate on 110 Moroccan patients with AS. Reliability for the 3-day test-retest was assessed using internal consistency by Cronbach's alpha coefficient and the intra-class correlation coefficient (ICC). External construct validity was assessed by correlation with pain, activity of disease and other keys variable. The reproducibility of the 15 items was satisfactory with a kappa statistics of agreement superior to 0.6. The ICC for IGF score reproducibility was good and reached 0.98 (IC 95%, 0.96-0.99). The internal consistency was at 0.991 with Cronbach's alpha coefficient. The construct validity showed a positive correlation between MAF and the axial (r = 0.34) and peripheral (r = 0.32) visual analogical scale, the Bath ankylosing spondylitis disease activity index (BASDAI) (r = 0.77), the first item of BASDAI (r = 0.85), the functional disability by the Bath ankylosing spondylitis functional index (r = 0.64), the erythrocyte sedimentation rate (r = 0.43) and the C reactive protein (r = 0.30) (for all P < 0.001). There was no statistical correlation between MAF and the other variables. The Arabic version of the MAF has good comprehensibility, internal consistency, reliability and validity for the evaluation of Arabic speaking patients with AS.Rheumatology International 12/2011; · 2.21 Impact Factor
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ABSTRACT: To study the factors associated with withdrawal of the and tumor necrosis factor alpha (anti-TNFα) biologics in the treatment of rheumatic diseases. Data from the Hong Kong Biologics Registry were retrieved. The cumulative rates of withdrawal of different biological agents were studied by Kaplan-Meier plot and the incidence of serious adverse events (SAEs) was calculated. Factors associated with the withdrawal of the anti-TNFα agents were studied by Cox regression. Between 2005 and 2013, 2059 courses of biologics were used in 1345 patients. After 3454 patient-years, 1171 (57%) courses were terminated because of clinical inefficacy (38.1%), SAEs (22.3%) and financial reasons (15.9%). The most frequent SAEs (per 100-patient-years) were allergy (2.90), serious infections (1.34), tuberculosis (0.93) and infusion/injection site reaction (0.75). Among the anti-TNFα agents, the cumulative probability of drug withdrawal for either inefficacy or SAEs in 5 years was highest with infliximab (IFX) (64.5%), followed by etanercept (ETN) (44.2%) and adalimumab (ADA) (36.9%). The incidence of serious infections and tuberculosis (per 100 patient-years) for IFX, ETN and ADA users was 1.99, 0.85 and 0.63; and 1.68, 0.43 and 0.85, respectively. Infusion/injection site reaction was highest with IFX (1.38/100 patient-years). Cox regression revealed increasing age, female sex, not having a diagnosis of spondyloarthritis (SpA) and IFX use were significantly associated with drug withdrawal for either inefficacy or SAEs. Rheumatoid arthritis (RA) had the highest hazard ratio for drug withdrawal but SpA was favorable for drug retention, after adjustment for age, sex, disease duration and the choice of anti-TNFα agents. In our registry, the retention rate of the anti-TNFα agents was lowest but the incidence of tuberculosis, serious infections and infusion reaction was highest with IFX. Older female patients with RA and the use of IFX were independently associated with drug withdrawal.International Journal of Rheumatic Diseases 12/2013; · 1.65 Impact Factor
1Rheumazentrum Ruhrgebiet, St. Josefs-
Krankenhaus, Herne, Germany;
2Leiden University Medical Center, Leiden,
Uta Kiltz, MD
Désirée van der Heijde, MD
Please address correspondence to:
Uta Kiltz, MD,
44652 Herne, Germany.
Received and accepted on July 29, 2009.
Clin Exp Rheumatol 2009; 27 (Suppl. 55):
© Copyright CLINICAL AND
EXPERIMENTAL RHEUMATOLOGY 2009.
Key words: Ankylosing spondylitis,
health-related quality of life,
Competing interests: none declared.
In this review the influence of rheu-
matoid arthritis (RA) and ankylosing
spondylitis (AS) on a wide range of
health-related quality of life (HRQoL)
domains will be described. The do-
mains most frequently studied are pain,
functional disability, fatigue and mental
problems. In addition, age and socio-
economic aspects such as employment
and economic status as well as educa-
tion affect patient-reported HRQoL.
Although many studies have assessed
the impact on HRQoL of a single dis-
ease state, either RA or AS, few studies
have focused on a direct comparison
between those both diagnostic groups.
In general, patients with RA and AS
report significant decrements in HR-
QoL in comparison with the general
population. It has been shown that the
magnitude of the impairment is similar
among both patients group.
There is a growing interest in describ-
ing and assessing quality of life (QoL),
particularly in chronic disabling con-
ditions. Health status describes the
impact of illness on a person’s ability
to participate in life. While health and
functional situation are predominantly
related to the physical condition, the
term “quality of life” includes the wish-
es, expectations and emotional respons-
es of the individual related to his/her
health. Gill and Feinstein suggest that
QoL rather than being a description of a
patient’s health status is a reflection of
the way in which patients perceive and
react to their health status (1). QoL en-
compasses the concept of health-related
QoL (HRQoL) which describes extend
to which one’s usual or expected physi-
cal, emotional and social well-being are
affected by a medical condition and its
treatment (2). It is important to notice
that the concept of HRQoL differ from
that of functional status although these
two constructs may highly correlate
for patients (3). Thus, HRQoL can be
thought of as the overall impact of the
illness and its treatment on patients, and
their response to these impacts.
HRQoL is not a single parameter but
rather a collection of different health
concepts that together paint a picture
how a disease affects a patient in daily
life. Although there is general agreement
that HRQoL is multidimensional, there
is no formal consensus on the domains
that should be included. The domains
most frequently studied are physical,
social, psychological, and occupational
well-being items. Thus, most preva-
lent QoL concerns in rheumatologic
diseases included pain, functional dis-
ability, fatigue and mental problems. In
addition, age and socio-economic fac-
tors such as employment and economic
status as well as education affect pa-
tient-reported HRQoL. Consequently,
there is a need to explore the burden of
rheumatoid arthritis (RA) and ankylos-
ing spondylitis (AS) focusing on a wide
range of health dimensions.
Measurement of QoL
Two basic approaches to measure QoL
are available: generic instruments that
provide a summary of QoL applicable
to all people (healthy and any disease),
and specific instruments that focus on
problems associated with single dis-
ease states (2). Commonly used generic
health status instruments are the Medi-
cal Outcomes Study 36-Item Short Form
(SF-36), EuroQoL (EQ-5D), Health
Assessment Questionnaire (HAQ) and
Health Assessment Questionnaire for
the spondyloarthropathies (HAQ-S) (4-
7). As a specific QoL instrument in pa-
tients with RA, the RAQoL can be used
(8). The Ankylosing Spondylitis Quali-
ty of Life (ASQoL) questionnaire is the
best studied disease-specific measure
available to assess HRQoL in AS pa-
tients (9). Both specific questionnaires
have proven validity and sensitivity for
assessment of changes in QoL and are
Health-related quality of life in patients with rheumatoid
arthritis and in patients with ankylosing spondylitis
U. Kiltz1 and D. van der Heijde2
Health-related quality of life in patients with RA and AS / U. Kiltz & D. van der Heijde
based on the needs-based model (9,
10). In this model, QoL is defined as
the extent to which individuals are able
to meet their needs. By concentrating
on needs, items are more likely to be
relevant to all patients regardless of
age, gender or employment status.
An important advance in HRQoL re-
search is the concept of “minimum clin-
ically important difference” (MCID),
defined as the smallest difference in
score on an HRQoL instrument that
patients perceive as beneficial and that
would mandate, in the absence of trou-
blesome side effects and excessive cost,
a change in the patient’s management.
Differences in scores smaller than the
MCID are considered unimportant, re-
gardless of whether statistical signifi-
cance is reached (11). Values for MCID
in domain and SF-36 summary scores
have been derived in RA and AS based
on correlations with patients-reported
improvements in global disease activity
The challenge in HRQoL measurement
is its multidimensional nature, which
takes into account not only how a per-
son functions physically, mentally and
socially, but also incorporates an evalu-
ative component that assesses a per-
son’s satisfaction with his or her current
health status. Health status instruments
can be used to monitor outcomes in
clinical practice, to assess the impact of
different diseases on HRQoL, for indi-
vidual decision making processes and
as an end point in clinical trials. HRQoL
assessments are particularly important
in the absence of a cure for RA and AS
and to provide evidence that therapy re-
ally makes people feel better.
HRQoL in patients with RA
RA is traditionally considered to be a
disease with a major impact on all as-
pects of HRQoL and may result in sig-
nificant disability, morbidity and early
mortality if untreated or inadequately
treated. Almost all patients report about
pain and functional disability during the
course of their disease considerably in-
fluencing their HRQoL. In a cross-sec-
tional survey from Norway it has been
demonstrated that pain is the area in
which almost 70% of the patients with
RA most desired an improvement (14).
Pain increased slightly with the dura-
tion of RA (0.03 units on visual analog
scale (VAS) per year (95% CI 0.02-
0.03)), while anti-tumour necrosis factor
(TNF)-α blocker therapy improved pain
by 0.53 to 0.70 units on VAS (15). Pro-
gressive deterioration in physical func-
tion is reported in longitudinal series of
RA patients prior to the introduction of
the new disease-modifying antirheumat-
ic drugs (DMARDs). Scott et al. dem-
onstrated average increases of 0.033 per
year in HAQ scores (16). Women with
RA have been reported to have more
functional disability than men (17).
Fatigue has been consistently mentioned
as an important outcome by patients
with RA, but it is seldom included in
routine clinical assessments. Clinically
important levels of fatigue are present
in 40-80% in RA patients (18). From
the patient’s perspective, fatigue has
consequences on all aspects of QoL and
is seen as important because fatigue af-
fects other outcomes like work or social
activity. Fatigue has been identified as
the consequence of disease that differ-
entiates best on a series of QoL aspects
such as disability and well-being (19).
Nevertheless, overlap of depression pre-
senting with symptoms of fatigue may
additionally influence HRQOL. Depres-
sive symptoms are frequent in RA and
may occur with at least mild severity in
up to 42% of RA patients (20).
Although the physical domain might be
most affected, the significant effect of
RA on the mental health should not be
underestimated. RA patients above the
age of 40 years had worse overall scores
for mental component summary (MCS)
score of the SF-36. Comparison with
the general population revealed a re-
duction of -0.27 for mental health meas-
ured by standardized difference scores
(s-scores), indicating a low to moderate
disease effect for mental health (21).
However, patient’s psychological state
needs to be assessed as a variable, inde-
pendent of physical impairment.
An improvement in clinical response
criteria is well known in patients with
active RA when treating with DMARDs
and biologics. Meanwhile, meaningful
impact on HRQoL parameters have
been demonstrated in randomized
controlled trials with DMARDs and
especially with biologics as well. Nor-
mally, improvement in QoL parameters
is accompanied by improvement in
Persistent active disease may lead to re-
duced productivity and increased rates
of work disability resulting in a worse
quality of life. Patients with RA are at
risk of work disability from the very
start of their symptoms. Prospective
cohorts show that 20–30% of patients
with RA become permanently work dis-
abled during the first 2–3 years of the
disease (22). Work disability appeared
to be 4–15 times higher than in the gen-
eral population (23). Females with RA
had a fourfold increased risk of work
disability compared to men (24).
HRQoL in patients with AS
AS the main entity of the spondyloar-
thritides (SpA), is a chronic condition
with a variable disease course (25).
Since AS usually starts in early adult-
hood, the average duration of disease is
longer compared to RA. Consequently,
the impact of AS on HRQoL of patients
can be important. The burden of illness
of AS is less well defined than for RA,
but there is an increasing awareness
that the impact of AS on HRQoL is
comparable to that in RA.
Patients with AS report significantly
impaired health on all scales of the SF-
36 compared with the general popula-
tion. The most prevalent HRQoL con-
cerns include stiffness, pain, fatigue
and sleep problems (26). Functional
disability is the main contributor to the
burden associated with AS. Compared
with patients with other medical condi-
tions, patients with AS have the low-
est scores in the physical domains (27).
Ward has indicated that longer disease
duration and increasing age are associ-
ated with decreased functioning, where-
as performing back exercises and hav-
ing a greater degree of social support
improves functioning (28). In this pro-
spective longitudinal study the HAQ-
S increased over a median of 5 years
at an average rate of 0.0168 units per
year. In a study from Norway, women
with AS reported worse physical func-
tioning, more physical limitations, and
a greater reduction in vitality measured
by SF-36 than men (29). However, the
Health-related quality of life in patients with RA and AS / U. Kiltz & D. van der Heijde
crude effect of the disease is greater in
men as shown by standard difference
scores of SF-36 between AS group and
general population (30).
Pain is considerable influencing HRQoL
in AS patients. 83% of the patients re-
port about any problems with pain, for
one third of them it is very important
(26). Again, women were 2 to 3 times
more likely than men to have greater
pain. Patients with AS reported signifi-
cantly more back pain than the global
pain in patients with RA (44 versus 25
mm on VAS pain), but pain is compara-
ble in the peripheral joints for the two
Fatigue has been described as a major
symptom in AS, with up to 65% of the
patients reporting (32). Van Tubergen et
al. showed that scores on the BASDAI
fatigue question were significantly as-
sociated with scores on several dimen-
sions of the SF-36 and with the ASQoL,
suggesting that HRQoL is influenced
by the degree of fatigue (33).
Although the physical aspects of health
seem to be most severely affected,
the disease impact on mental health is
considerable. A study by Barlow et al.
showed that one third of the AS patients
reported a high level of depressive
symptoms undermining the stereotype
of the “typical” AS patient as being less
depressed than other people with other
forms of arthritis (34). In addition, dis-
ease status scores like BASDAI cor-
relates significantly with anxiety and
depression (35). The disease impact on
HRQoL is considerable especially in
those with less education (30). Thus,
special attention should be paid to this
aspect and educating patients about the
disease may play an important role in
coping with the disease.
In a variety of studies significant as-
sociation between HRQoL improve-
ments and clinical response criteria
has been shown in patients with active
AS receiving TNF-α blockers therapy
(27). As expected, the physical com-
ponent summary (PCS) of the SF-36
has changed more than the MCS due to
therapy in these studies.
The improvement of HRQoL dur-
ing treatment with TNF-α blockers is
accompanied by significant improve-
ment in productivity and reduced work-
day loss among employed patients with
AS (36). Nevertheless, AS may cause
work disability up to 36% primarily
depending on disease duration (37).
The dependence from disease duration
is important to notice since AS evolves
slowly and progressively mainly in pa-
tients in their 3rd decades. Employment
is 11% (OR: 0.82;95% CI: 0.78-0.87)
lower and work disability 15% (OR:
3.10; 95% CI: 2.77-3.42) higher than
expected in the general Dutch popula-
tion (38). Interestingly, while income
was not associated with reduced QoL,
income loss due to work disability re-
sulted in a worse HRQoL (39).
As stated above, pain and impaired mo-
bility as well as fatigue and depression
are common features of both RA and AS.
A direct comparison of HRQoL between
RA and AS has been made in only few
studies. According to a Dutch study the
impact on several dimensions of SF-36
in patients with RA and AS of working
age is comparable (40). In addition, the
level of fatigue and the way patients cope
with stressors of the disease (measured
by the Multidimensional Fatigue Inven-
tory (MFI) and the Coping with Rheu-
matic Stressors (CORS) instrument) is
also similar. In a recent study, patients
with RA and chronic arthritides includ-
ing patients with SpA reported the very
same poor HRQoL scores compared to
an age-standardized general population
(0.810 and 0.815 versus 0.903 on a 0-1
These findings confirm the conclusion
of the German rheumatological data-
base that RA and AS generate similar
amounts of disability, pain, and impact
on well-being (42). Patients with RA
and AS were equally disabled in func-
tions like washing and drying oneself
or standing in line. Comparison of pain
intensity between age and sex matched
groups of patients with RA and AS re-
vealed that for patients younger than
70 years there is little difference be-
tween both disease groups or between
women and men (severe pain (VAS≥7)
in female RA and AS patients: 33.8 and
34.2%, and male RA and AS patients:
33.1 and 32.7%). However, for higher
age groups there is a marked difference
between women and men in both diag-
nostic groups. This gender difference
is much more striking than the differ-
ence between AS and RA (severe pain
in female RA and AS patients: 40.8 and
44.6%, and male RA and AS patients:
27.0 and 29.8%).
Treatment is one of the most important
factors which can influence the HRQoL
of the patients. There is one retrospec-
tive meta-analysis on the efficacy of
TNF-blockers in RA versus AS. Larger
improvements in HRQoL in SpA pa-
tients have been attributed to the rela-
tively better efficacy of TNF-blockers
in the treatment of SpA (43).
The socio-economic consequences in
RA and AS have been compared recently
(44). Work loss is one of the most impor-
tant outcomes of chronic inflammatory
rheumatic diseases. In addition, work
status is after disease characteristics, the
most important determinant influenc-
ing HRQoL in patients with RA and AS
(40). The lowest standardized employ-
ment ratios (SER) of 0.78 (1.0=popu-
lation) has been calculated in patients
with RA compared to patients with AS
(0.94) in a study by Mau et al. (44). The
SER declined significantly with disease
duration. In female RA patients the SER
is 0.93 (95%CI: 0.90-0.95) after ≤5
years of disease and declined to 0.56
(95%CI: 0.54-0.59) after >10 years. No
significant difference from the popula-
tion is found in the SER in AS patients
with a disease duration ≤10 years. In pa-
tients with longer-lasting AS, there is a
slightly higher chance of employment in
AS compared to RA (SER 0.88, 95%CI:
0.83-0.92 for men; SER 0.91, 95%CI:
0.84-0.99 for women).
Patients with RA and AS report sig-
nificant reduction in HRQoL in com-
parison with the general population. It
has been shown that the magnitude of
the impairment is similar among both
patients group. The decreases in HR-
QoL are attributed to various domains,
mainly pain, impairment in physical
function, fatigue and mental health.
These domains and the strategies pa-
tients use to cope with disease burden
influence socioeconomic factors. Thus,
maintenance of physical function is no
longer the only treatment goal for RA
and AS but also to improve, restore, and
Health-related quality of life in patients with RA and AS / U. Kiltz & D. van der Heijde
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