A longitudinal study of disease activity and functional status in a hospital cohort of patients with ankylosing spondylitis
L. P. Robertson and
M. J. Davis1
Rheumatology, Bristol Royal Infirmary, Bristol and 1 Rheumatology, Royal Cornwall Hospital, Truro, Cornwall, UK.
Correspondence to: L. P. Robertson. E-mail: lindsay.robertson{at}ubht.swest.nhs.uk
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Abstract
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Objective. To evaluate changes in functional status and disease activity and their determinants in patients with ankylosing spondylitis (AS) attending hospital, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI).
Methods. Patients completed BASDAI and BASFI questionnaires annually from 1996 to 2001. Demographic and clinical data were collected. The mean first and last recorded scores were compared. The change per year and area under the curve per year for the BASDAI and BASFI were calculated. Relationships between demographic, clinical and longitudinal BASDAI/BASFI data were examined. Subgroup analyses were performed using the cross-sectional and longitudinal data.
Results. Two hundred and seventy-nine BASDAI and 322 BASFI questionnaires were analysed. The BASFI increased [mean change 6.15, 95% confidence interval (CI) 1.9, 10.3, P = 0.005] but the BASDAI did not (mean change 0.87, 95% CI 3.96, 5.7, P = 0.71). First recorded scores were the best predictors of the cumulative scores per year. Patients with peripheral joint (P = 0.01) and hip (P<0.001) disease had higher mean BASFI scores. Males (P<0.001) and patients with spinal disease alone (P = 0.0014), iritis (P = 0.005) and late-onset AS (P = 0.002) became more functionally impaired over time.
Conclusions. Disease activity in this AS cohort remained relatively constant but there was functional decline. Initial BASDAI/FI can predict a severe disease course. PJD patients with peripheral joint disease were more functionally impaired, but deteriorated less than spinal disease alone patients. Iritis and late onset disease may be severity markers for functional impairment.
KEY WORDS: Ankylosing spondylitis, BASDAI, BASFI
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Introduction
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Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease affecting the sacroiliac joints, spine, peripheral joints and entheses. There is a paucity of published data describing the natural history, course and prognosis of AS. It is a difficult area to study because of the heterogeneous nature of AS, long disease duration and, until recently, lack of appropriate, validated outcome measures.
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) [1, 2] are standardized, reproducible and validated measures of disease activity and functional impairment. They have principally been used in cross-sectional studies. This study examined serial measures of the BASDAI and BASFI in a hospital cohort of AS patients. These were collected retrospectively and recorded over a 5-yr period. The aim of this study was to provide information on the course and natural history of AS.
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Materials and methods
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Patient sample
Patients attending the AS specialist clinic at the Royal Cornwall Hospital, Truro, diagnosed with AS (modified New York criteria) [3] were sampled.
Patient selection and criteria for admission to study
Patients completed the BASDAI and BASFI questionnaires annually from 1996. Patients with AS who had completed three or more BASDAI and/or BASFI questionnaires on separate occasions from 1996 to 2001 were included (Table 1). Patient case notes were reviewed. Information not available from the clinical notes was obtained from patients at clinic appointments. Informed patient consent was not required or obtained for the study. Ethical approval from the Cornwall Local Research Ethics Committee was granted.
Data collection
Demographic data were collected: age, sex, disease duration (taken from when symptoms first began) and age at onset of AS. The clinical characteristics were recorded (Table 2). BASFI and BASDAI scores were calculated. The visual analogue scores of the BASDAI/BASFI were scored out of 100 rather than 10. This was done for ease of data handling so that the values of the change per yr scores were not extremely small.
Data analysis
BASDAI and BASFI data were analysed cross-sectionally and longitudinally for the whole cohort and subgroups. The KolmogorovSmirnov test was used to assess normality of distribution with the significance level of 0.05. For cross-sectional analysis, unpaired t-tests were used. For the longitudinal analysis, paired t-tests, the change per year (change/yr) and area under the curve per year (AUC/yr) were calculated.
To examine possible relationships between demographic and/or clinical data and the longitudinal BASDAI/BASFI data, stepwise linear regression analysis was used to identify the independent impact of selected findings on the AUC/yr. P values of less than 0.05 were considered significant. Data were analysed using Microsoft Excel 2001 and SPSS software version 11.0 (SPSS, Woking, UK).
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Results
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Demographic and clinical data
A total of 112 patient case notes were screened. Seventy-four patients were included. Thirty-eight patients were excluded because they had not completed the required number of questionnaires. Table 1 shows how many assessments patients completed over the 5-yr period. Of the 74 study patients, 56 were male and 18 female (M:F ratio = 3.1:1), mean age was 48.5±11.24 yr, disease duration 21.1±10.63 yr and age at disease onset 27.9±9.04 yr.
Table 2 gives the clinical characteristics of the cohort. Nine out of the eleven joint arthroplasties were for hip disease, two patients had bilateral hip replacements and one patient had bilateral knee replacements. Patients with hip disease were more likely to be attending regular hydrotherapy [odds ratio 3.39, 95% confidence interval (CI) 1.4, 11.1]. Of the 11 joint replacements, six were carried out in four patients during the 5-yr period when the data were collected. Of these patients, only one had a large fall in his BASDAI after hip replacement (from 68.2 to 53.4). This patient unfortunately did not have BASFI scores completed after surgery. The other three patients BASDAI/BASFI scores remained relatively unchanged. Of the 58 patients taking NSAIDs, 12 were taking cyclooxgenase 2 (COX-2)-selective inhibitors. The majority of patients taking NSAIDs were doing so continuously.
BASDAI and BASFI data
Whole cohort
Two hundred and seventy-nine BASDAI scores and 322 BASFI scores were recorded, with a total follow-up time of 314 and 306 patient years respectively. There was no difference between the mean first and last recorded BASDAI for the whole cohort (mean change 0.87, 95% CI 3.96, 5.7, P = 0.71; mean change/yr 0.06, 95% CI 1.14, 1.26). The mean BASFI increased over the study period [mean change 6.15, 95% CI 1.9, 10.3, P = 0.005 (Table 3), mean change/yr 1.26, 95% CI 0.13, 2.39]. Figures 1 and 2 illustrate the mean scores over time and the AUC.
In the regression analysis for the AUC/yr BASDAI, the first BASDAI (ß = 0.54, P<0.0001), first BASFI (ß = 0.202, P<0.001) and iritis (ß = 5.555, P = 0.041) gave the best-fit model. The proportion of the variance explained (R2) was 75.1%. For the AUC/yr BASFI, first BASFI (ß = 0.86, P<0.0001) and age at onset (ß = 0.29, P = 0.07) gave the best fit. The proportion of the variance explained (R2) was 82.4%. Repeat regression analysis for age of onset subgroups did not give a better fit for the data than the models for the sample as a whole.
Subgroups
There were no differences in the mean first BASDAI scores between the patient subgroups, with the exception that employed patients had a lower mean first BASDAI than unemployed patients (41.90±23.48 vs 54.91±26.99, P = 0.035). The mean first BASFI scores in patients with peripheral joint disease (PJD) were higher than those in patients without PJD (54.66±31.57 vs 38.01±26.67, P = 0.01), those with hip disease (64.19±30.78 vs 39.42±27.21, P<0.001) and those with total joint replacement (TJR) (77.94±36.19 vs 41.92±28.29, P<0.001). Employed patients had a lower mean first BASFI than unemployed patients (30.44±25.80 vs 61.73±26.66, P<0.001).
There were no differences between the mean first and last recorded BASDAI scores and the mean change/yr BASDAI for the subgroups. However the mean AUC/yr BASDAI in patients with TJR was higher than that in those without TJR (61.82±11.91 vs 45.13±22.46, P = 0.002) and lower in employed patients compared with those who were unemployed (38.29±20.23 vs 56.03±20.31, P<0.001).
There were increases in BASFI over the study period in males, patients with onset at
30 yr, patients with iritis, patients without PJD, patients without hip disease, patients without TJR and patients not attending regular hydrotherapy, and in the unemployed (Table 3). The NSAID and non-NSAID users BASFI scores worsened over time, the latter more than the former, although this difference was not significant (P = 0.34).
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Discussion
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Whole cohort
When considering the results of this study, it should be born in mind that the patients in our cohort were attending a specialist clinic and therefore were at the severe end of the disease spectrum of AS. Milder cases were unlikely to be included. Disease activity remained relatively constant. This has also been found using a disease activity score that formed the basis of the BASDAI [4]. The BASFI scores increased over time and the whole cohort, on average, was more functionally impaired at the end of the study period. This indicates that, despite disease activity being relatively stable in patients with AS, there is still the capacity for function to decline.
The first recorded scores were the best predictors of the cumulative scores per year, with little influence of other disease parameters. The presence of iritis appeared to decrease the BASDAI (negative ß value), which does not correspond to the functional data results. However, iritis only just reached significance in the regression analysis and therefore the overall effect is likely to be small. Furthermore, it is possible that the presence of a history of iritis may interfere with the association between the BASDAI and the BASFI, so that increased disease activity does not necessarily mean increased functional impairment and vice versa.
Subgroups
Our data support the generally accepted concept that females have less severe disease than males [5] but are in disagreement with BASDAI and BASFI centile charts using the Bath AS database. This showed that females had greater disease activity and functional impairment than males [6]. However, the population used to construct these charts was a mixture of hospital-attending and non-hospital-attending patients. This makes direct comparison of the results difficult.
The differences in the mean first BASFI between patients with and without PJD, hip disease and TJR are in keeping with the known more severe prognosis in these patient groups [7, 8]. It has been demonstrated that patients with hip disease as measured by the Bath Ankylosing Spondylitis Radiology Index (BASRI) have more severe spinal disease than those without hip involvement [9]. Patients with total hip arthroplasty have also been reported to have higher BASFI scores than those without [10]. The functional scores of the patients with PJD did not change significantly over the study period as they did in the groups with spinal disease alone. It is possible that a ceiling effect is an explanation for this. Alternatively, joint arthroplasties during the study period may have prevented some of the PJD patients deteriorating further. However, inspection of the actual BASDAI/BASFI scores of the arthroplasty patients does not support this.
It is generally accepted that patients with a younger disease onset have a more severe disease evolution than those with older onset. However, some of the data upon which this is based did not assess patients from a functional point of view [11]. Cross-sectional data from the Bath AS database suggest that age at onset of AS influences disease activity but does not affect functional severity [8]. Our results differ in that there was no influence on disease activity and the later onset group became more functionally impaired over the study period compared with the younger onset group. Therefore, in our hospital-attending AS population an older age at onset was not a marker for milder disease and the younger onset group did not progress as much as expected.
Iritis has been associated with restricted mobility of the spine [12] and with more widespread spinal disease [13]. More recently, AS patients with iritis were found to have a more severe radiological outcome than those without iritis [14]. Kirwan et al. suggested there may be two distinct disease groups of AS patients: those with and without frequent extraspinal manifestations [15]. The BASFI data from this cohort are in agreement with these observations.
The hip disease group improved functionally, although the difference was not significant. Some of these patients underwent hip arthroplasty during the follow-up period, which may explain this finding. Alternatively, by attending regular hydrotherapy (which they were more likely to be than those without hip disease) their functional deterioration was slowed.
The number of patients taking COX-2-selective inhibitors was small and insufficient for us to draw any conclusions from their effect in AS compared with standard NSAIDs. A recent study has highlighted the possible importance of NSAIDs as disease-modifying drugs in AS [16]. Our functional data lend support for this, but the support is weakened by the lack of significant change in the BASDAI.
The follow-up time for the study was, on average, 4 yr for each patient. This is a relatively short period in the disease course of AS. Therefore, studies with longer follow-up are required, ideally with an inception cohort, although the logistic difficulties of such long-term follow-up are considerable. Carette et al. suggested that it is the first 10 yr of disease that predicts the further disease course over time [12]. It is only prospective data from baseline that will be able to confirm this with further certainty.
The authors have declared no conflicts of interest.
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Submitted 5 January 2004;
revised version accepted 23 July 2004.