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,
1 Hôpital National de Saint Maurice, avenue du Vals d'Osne, 94410 Saint-Maurice,
2 Hôpital Cochin, 75014 Paris, France,
3 Division of Rheumatology, School of Medicine, Hannover, D-3000 Hannover 61, Germany and
4 Department of Rheumatology, University Hospital, Ghent, Belgium
Correspondence to:
A. Calin, Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK.
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Abstract
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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.
KEY WORDS: Ankylosing spondylitis, Disease activity, Bath Ankylosing Spondylitis Disease Activity Index, Content validity.
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Introduction
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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 [14]. 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 attributes 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 [1114]). 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 scale (010) 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).
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Patients and methods
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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].
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
(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.
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Results
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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 S.D. 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.
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TABLE 3. Changes during the study in the evaluated variables by treatment groups (placebo = 121 patients, NSAID = 352 patients)
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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, -0.03) at zero time and correlations (1.0, 0.01, -0.01, 0.01, 0.0) at last entry.
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TABLE 5. Correlations between the variables and the principal axes (PCA performed on the changes in the variables)
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The five components of the BASDAI and the BASDAI itself on the best principal plane accounted for 76% of the total variance.
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Discussion
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Over recent years, there has been increased interest in outcomes research in the rheumatic diseases, culminating in a series of OMERACT meetings [14]. 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 [516]. 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 approachagreement 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.
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Acknowledgments
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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, the support of the Colonel W. W. Pilkington Charitable Trust and the John Coates Charitable Trust is gratefully acknowledged.
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Submitted 16 July 1998;
revised version accepted 1 April 1999.