Rheumatology 1999;38:878–882
Defining disease activity in ankylosing
spondylitis: is a combination of variables (Bath
Ankylosing Spondylitis Disease Activity Index)
an appropriate instrument?
A. Calin, J.-P. Nakache1, A. Gueguen1, H. Zeidler3, H. Mielants4
and M. Dougados2
Royal National Hospital for Rheumatic Diseases, Bath, UK, 1Hôpital National
de Saint Maurice, avenue du Vals d’Osne, 94410 Saint-Maurice, 2Hôpital
Cochin, 75014 Paris, France, 3Division of Rheumatology, School of Medicine,
Hannover, D-3000 Hannover 61, Germany and 4Department of Rheumatology,
University Hospital, Ghent, Belgium
Abstract
Objective. Disease activity has been defined using a self-administered instrument, focusing
on fatigue, axial pain, peripheral pain, enthesopathy and morning stiffness [Bath Ankylosing
Spondylitis Disease Activity Index (BASDAI )]. This validated instrument is simple and takes
40 s to complete, but whether the index is an accurate expression of the component parts, or
whether additional weighting would enhance its efficacy, is unclear.
Methods. Four hundred and seventy-three patients with ankylosing spondylitis received
placebo or active non-steroidal anti-inflammatory drug (NSAID) for 6 weeks, and changes
between entry and completion were captured by BASDAI and the individual components.
Principle component analysis (PCA) was used to explore the best combinations of variables in
decreasing order of explained total dispersion and to assess whether a single sum (or algebraic
expression) best defined disease activity status.
Results. At entry, the correlation between BASDAI and the first axis was 0.99, 0.11 with
the second, and zero thereafter. Data at study end and relating to change revealed a 100%
correlation (R = 1) between the first axis and the sum, with zero for the remainder.
Conclusions. The data support BASDAI as being a valid and appropriate composite to
define disease activity in ankylosing spondylitis. Developed as a simple sum of its components,
BASDAI has excellent content validity.
K : Ankylosing spondylitis, Disease activity, Bath Ankylosing Spondylitis Disease
Activity Index, Content validity.
Defining outcome in chronic disease is notoriously
difficult. In rheumatological practice, relevant end
points, such as loss of renal function in systemic lupus
erythematosus, may exist, whilst in other conditions,
such as rheumatoid disease, laboratory variables may
be surrogate markers for underlying disease activity
[1–4]. By contrast, in ankylosing spondylitis, the situation is more complicated, given that process markers
are frequently absent [e.g. erythrocyte sedimentation
rate ( ESR)] and few end points are clearly defined. No
consensus exists as to how many variables are required
to provide a full clinical picture and the relative attrib-
utes between individual outcomes, or composite indices
combining a variety of variables, remain unclear [5].
Many single-component measures have been used in the
assessment of ankylosing spondylitis in terms of evaluating mobility, disease activity, radiological status and
other variables. More recently, a series of validated,
composite indices have been developed which focus on
different aspects of disease (i.e. function [6, 7], metrology [8], radiology [9], global status [10] and disease
activity [11–14]). Finally, validated outcome reference
curves for ankylosing spondylitis have now been
developed [15].
Disease activity has been evaluated by assessment of
pain, fatigue, stiffness and discomfort. Specifically, the
Bath Ankylosing Spondylitis Disease Activity Index
(BASDAI ) [14] was developed as a composite index
( Fig. 1), consisting of an evaluation on a visual analogue
Submitted 16 July 1998; revised version accepted 1 April 1999.
Correspondence to: A. Calin, Royal National Hospital for
Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK.
878
© 1999 British Society for Rheumatology
Defining disease activity in ankylosing spondylitis
879
F. 1. The Bath Ankylosing Spondylitis Disease Activity Index.
scale (0–10) of fatigue, axial pain, peripheral pain,
stiffness and enthesopathy. More recently, the instrument has been translated into several languages and has
now been validated in French [16 ]. However, it remains
unclear whether the index is an accurate expression of
the component parts, or whether weighting would provide enhanced efficacy.
The purpose of the present study was to analyse,
prospectively, disease activity in two cohorts of patients
over a 6 week period. One group received placebo and
the other, active non-steroidal anti-inflammatory drug
(NSAID).
Patients and methods
Patient population
Out-patients with active disease fulfilling the modified
New York criteria [17] for ankylosing spondylitis were
recruited. Active disease was defined by the requirement
of daily intake of NSAID during the preceding month.
The characteristics of the 473 cases are summarized
in Table 1. Only individuals with axial disease were
accepted. Those with active peripheral involvement were
excluded from the study.
Study design
The investigation was a longitudinal study of 6 weeks
duration, during which a complete examination was
performed by the same investigator at baseline, and 1,
3 and 6 weeks thereafter. Following a wash-out, patients
who flared by 30% over baseline received one of two
NSAIDs (piroxicam or meloxicam) or a placebo. The
double-blind, placebo-controlled study was of 6 weeks
duration [18].
A. Calin et al.
880
T 1. Characteristics of patients
Total (n = 473)
Placebo (n = 121)
NSAID (n = 352)
78
42.6
12.2
28
27
27
86
72
40.1
11.9
30
26
26
90
80
43.5
12.3
27
28
28
85
Male (%)
Age (yr)
Disease duration (yr)
Peripheral joint disease (%)a
Uveitis (%)a
Family history (%)
HLA B27 (%)
aRefers to past history.
T 2. Assessment criteria
Outcome measurements
Patient global ( VAS )
Physician global ( VAS )
Overall pain ( VAS)
Spinal pain
Cervical
Dorsal
Lumbar
Night pain
Morning stiffness
Functional status
BASFI ( VAS)
ASFI
Disease Activity Index
BASDAI
0–100 mm
0–100 mm
0–100 mm
Metrology
Schober
Finger to floor
Occiput
Chest wall
Laboratory tests
CRP
Haemoglobin
Platelets
Analgesic consumption (no. of pills/day)
0–3
0–3
0–3
0–3
Minutes
cm
cm
cm
cm
0–10
0–60
0–10
VAS, visual analogue scale; ASFI, functional index of Dougados et al. [6 ]; BASFI, Bath Ankylosing Spondylitis Functional Index [7];
BASDAI, Bath Ankylosing Spondylitis Disease Activity Index [14].
T 3. Changes during the study in the evaluated variables by treatment groups (placebo = 121 patients, NSAID = 352 patients)
Treatment group
Placebo
Variables
Global assessment
Patient ( VAS)
Doctor ( VAS )
Pain
VAS
Cervical
Spinal pain
Dorsal
Lumbar
Inflammation
Night pain
Morning stiffness
CRP
Haemoglobin
Platelets
Functional disability
ASFI
BASFI
Range of motion
Schober test
Finger to floor distance
Occipital to wall
Chest expansion
BASDAI (total score)
Analgesic consumption
Number of pills/day
NSAID
Baseline
Changes
Baseline
Changes
62 ± 20
57 ± 20
−7 ± 30
−7 ± 27
64 ± 19
58 ± 18
−29 ± 27
−24 ± 26
0.0001
0.0001
1.6 ± 1.1
−0.0 ± 0.9
1.6 ± 1.1
−0.5 ± 1.0
0.0001
1.7 ± 1.1
5.6 ± 2.5
−0.1 ± 1.0
−0.1 ± 1.2
1.2 ± 1.1
5.8 ± 2.5
−0.6 ± 1.1
−0.9 ± 1.1
0.0001
0.0001
2.8 ± 0.7
88 ± 77
11.2 ± 11.0
8.6 ± 0.7
276×103 ± 69×103
−0.0 ± 0.9
−7 ± 29
4.2 ± 13.6
0.0 ± 0.5
2 ± 36
2.7 ± 0.7
93 ± 151
14.2. ± 7.1
8.7 ± 1.0
274×103 ± 68×103
−0.7 ± 0.9
−22 ± 31
0.4 ± 13.7
0.1 ± 0.7
4 ± 39
0.0001
0.0001
0.0075
0.5417
0.1589
15.7 ± 6.9
51 ± 24
+0.5 ± 6.3
+0.4 ± 20.4
12.1 ± 7.9
51 ± 21
−3.0 ± 5.9
−12.7 ± 20.1
0.0001
0.0001
12.8 ± 1.5
24.8 ± 17.0
5.6 ± 5.5
3.8 ± 2.2
317 ± 274
+0.1 ± 1.4
+0.5 ± 11.0
+0.1 ± 1.9
−0.2 ± 1.5
−22 ± 74
12.7 ± 1.6
26.2 ± 15.4
6.1 ± 5.9
3.6 ± 2.1
258 ± 89
+0.3 ± 1.2
+3.5 ± 9.7
−0.5 ± 3.4
+0.4 ± 1.7
−76 ± 105
0.0775
0.0006
0.0161
0.0002
0.0002
2.2 ± 2.1
1.9 ± 2.1
1.1 ± 1.6
0.9 ± 1.5
0.0001
P
Defining disease activity in ankylosing spondylitis
Assessment criteria
The outcome assessments are summarized in Table 2.
Disease activity was assessed with the BASDAI [14], a
self-administered instrument with six questions relating
to individual domains of fatigue, spinal pain, joint pain
and symptoms, together with perception of pain relating
to the entheses (i.e. tender bony sites around the body)
and two aspects of morning stiffness (quantity and
quality) (Fig. 1). In addition, the individual components
relating to pain, stiffness, fatigue and discomfort were
analysed separately.
Statistical approach
In order to compare the baseline data and results at the
last visit, t-tests were performed.
The internal consistency of the BASDAI instruments
was evaluated using Cronbach coefficient a (CCA).
This provides an indication of the correlation existing
between all the components of a given index. By convention, 0.70 is the minimum value for an acceptable level
of agreement.
A principle component analysis (PCA) was used to
explore the best combination of variables and to assess
whether a simple sum (as opposed to an algebraic
expression) would best define global disease activity
status. For this purpose, the PCA has been performed
on the components of the BASDAI. The principal axes
of the PCA which are, by construction, the best combinations of these components were then correlated with
the BASDAI.
Results
Patients and study design
Of the 603 screened patients, 473 were included in the
study. During the 6 weeks of the study, 110 patients
withdrew either due to lack of efficacy and/or toxicity
or for other reasons.
The main characteristics of the patients by treatment
group are summarized in Table 1. There was no statistically significant difference between the two groups apart
from an age difference (40.1 vs 43.5 yr).
Table 3 provides the mean and the .. of the changes
(0 time and last visit) of the variables for the two
treatment groups and the P values resulting from the
comparison of these changes.
Internal consistency of the BASDAI instruments was
good with a CCA of 0.84 for the changes in this index
( Table 4). The CCA values were 0.76 and 0.90 when
dealing with the values between 0 and 6 weeks,
respectively.
Table 5 provides the results of the PCA performed on
the changes in the components of the BASDAI, revealing
a correlation of one between BASDAI and the first
principal axis, and a practically zero correlation with
the remaining axes. Two separate PCA analyses were
also performed at zero time and at last visit, providing
similar results: correlations (0.99, 0.10, 0.0, −0.01,
881
T 4. Internal consistency of the BASDAI instrument (analysis of
the changes between 0 and 6 weeks)
Cronbach coefficient alpha: 0.84
Deleted sub-component
Correlation with total
Alpha
0.66
0.75
0.47
0.66
0.68
0.80
0.78
0.85
0.80
0.80
Fatigue
Axial pain
Peripheral pain
Discomfort
Stiffness, swell
T 5. Correlations between the variables and the principal axes
(PCA performed on the changes in the variables)
Principal axes
Variables
Fatigue
Axial pain
Peripheral pain
Discomfort
Stiff, swelling
BASDAI
F1
F2
F3
F4
F5
0.79
0.87
0.62
0.79
0.82
1.00
−0.12
−0.17
0.76
0.03
−0.32
0.03
0.48
0.13
0.05
−0.49
−0.16
−0.01
0.33
−0.21
−0.15
0.36
−0.33
0.00
−0.14
0.40
−0.06
0.06
−0.30
−0.01
−0.03) at zero time and correlations (1.0, 0.01, −0.01,
0.01, 0.0) at last entry.
The five components of the BASDAI and the
BASDAI itself on the best principal plane accounted
for 76% of the total variance.
Discussion
Over recent years, there has been increased interest in
outcomes research in the rheumatic diseases, culminating
in a series of OMERACT meetings [1–4]. Parallel to
this, attempts by individual groups have been made to
address the various components of disease status in
ankylosing spondylitis with various publications from
The Netherlands, the UK and France [5–16 ]. Indeed,
we have recently produced reference centile charts for
measures of outcome in this disease [15]. Moreover,
preliminary core sets for end points in ankylosing spondylitis were recommended following a delphi/consensus
approach—agreement reached after discussion with academics, clinicians and patients with ankylosing spondylitis [5].
Herein, we have had the opportunity of studying
several hundred patients over a 6 week period.
Individuals received either placebo or an NSAID. The
data support BASDAI as being valid and an appropriate
composite to define disease activity in ankylosing spondylitis. Developed as a simple sum of its components,
BASDAI has excellent content validity.
Acknowledgements
This study would not have been possible without the
generous support of Boehringer Ingelheim, who allowed
us to analyse numerous outcome measurements during
their controlled evaluation of meloxicam, an active
comparator and placebo in ankylosing spondylitis. Also,
882
A. Calin et al.
the support of the Colonel W. W. Pilkington Charitable
Trust and the John Coates Charitable Trust is gratefully
acknowledged.
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