A simplified version of Ankylosing Spondylitis Disease Activity Score (ASDAS) in patients with ankylosing spondylitis

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1 DOI /s ORIGINAL ARTICLE A simplified version of Ankylosing Spondylitis Disease Activity Score (ASDAS) in patients with ankylosing spondylitis Fernando A. Sommerfleck & Emilce E. Schneeberger & Emilio E. Buschiazzo & José A. Maldonado Cocco & Gustavo Citera Received: 5 May 2012 /Revised: 17 July 2012 /Accepted: 2 August 2012 # Clinical Rheumatology 2012 Abstract This study aimed to develop a simplified version (ASDAS). The study included consecutive patients with ankylosing spondylitis according to modified New York and/or Assessment in Ankylosing Spondylitis 2009 criteria. Sociodemographic data and characteristics of the disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing Spondylitis Quality of Life (ASQoL)) and erythrocyte sedimentation rate (ESR) were collected. ASDAS simplified version (SASDAS) was calculated as the simple linear sum of the five components of ASDAS which include: patient global assessment using visual analogue scale, back pain (BASDAI question no. 2), peripheral pain and swelling (BASDAI question no. 3), morning stiffness (BASDAI question no. 6), and ESR in millimeters per hour, divided by 10 so as to make it equivalent to the other scale's components. Eighty-six patients were included: 69 (80.2 %) were men with a median age F. A. Sommerfleck : E. E. Schneeberger : E. E. Buschiazzo : J. A. Maldonado Cocco : G. Citera (*) Section of Rheumatology, Instituto de Rehabilitación Psicofísica, Echeverría 955, 1428 Buenos Aires, Argentina gustavocitera@gmail.com F. A. Sommerfleck fersommer@yahoo.com.ar E. E. Schneeberger eschneeb@gmail.com E. E. Buschiazzo emilio.buschiazzo@gmail.com J. A. Maldonado Cocco Maldonado.cocco@fibertel.com.ar of 46 years and median disease duration of 19 years. SAS- DAS showed an excellent correlation with the ASDAS (r0 0.93). SASDAS also showed a good correlation with night pain (r00.60), global pain (r00.69), ASQoL (r00.70), BASFI (r00.75), and BASDAI (r00.96). Using ASDAS cut-off values previously suggested, the corresponding cutoff values for SASDAS were as follows: from 0 to 7.8 (inactive disease), from 7.9 to 13.8 (moderate disease activity), from 13.9 to 27.6 (high disease activity), and above 27.6 (very high disease activity) with optimum sensitivity and specificity. SASDAS showed an excellent correlation with conventional clinical measures of disease activity, and it can be easily calculated and is simple to use in daily clinical practice. Keywords Ankylosing spondylitis. Disease activity. Monitoring disease Introduction Ankylosing spondylitis (AS) is the prototype of the spondyloarthritis and is characterized for affecting mainly young adults between 15 and 30 years old [1 4]. The course of AS is usually progressive with consequent functional deterioration and disability associated with spinal ankylosis and compromise of hip joints which leads to a decrease in the quality of life and a high socioeconomic impact for the patient and the society [5 7]. Therefore, a stringent monitoring of disease activity is essential and, for this purpose, we have several tools, among which the two most frequently used are bath ankylosing spondylitis disease activity index (BASDAI) [8] and, more recently,

2 ankylosing spondylitis disease activity score (ASDAS) [9]. The ASDAS was developed by Assessment in Ankylosing Spondylitis (ASAS) group. It is a composite index made up of three BASDAI questions, patient global assessment using visual analogue scale (VAS), and also an objective laboratory variable such as erythrocyte sedimentation rate (ESR) or C-reactive protein. Though several studies showed that the ASDAS is reliable and reproducible, and in some cases better than BASDAI [10, 11], it is difficult to calculate without using a calculator and therefore arduous to use during daily clinical practice. Currently, there are no simplified indexes to follow-up patient with AS; nevertheless, for measuring disease activity in rheumatoid arthritis patients, Smolen et al. developed the Simplified Disease Activity Index (SDAI) [12]. The SDAI is the sum of five outcome parameters. It is comparable with the DAS28, which easier to calculate and does not require a calculator. Therefore, we decided to develop a simplified version (SASDAS), correlate it with the ASDAS and with conventional clinical measures of disease activity, and establish cut-off points based on the preestablished ASDAS cut-off points [13]. Material and methods The study included consecutive ambulatory patients, older than 16 years old, male and female, and diagnosed with AS according to modified New York [14] and/or ASAS 2009 [15] criteria for axial spondyloarthritis from the Department of Rheumatology of Instituto de Rehabilitación Psicofísica between November 2008 and August Data for each patient were collected on a preselected template. Sociodemographic data (age and gender), disease characteristics, disease duration, and treatments received were recorded. A full physical examination was performed and measures of disease activity such as morning stiffness, night pain, global pain, and BASDAI were performed. Furthermore, Ankylosing Spondylitis Quality of Life (ASQoL) [16] was used to assess the quality of life and the Bath Ankylosing Spondylitis Functional Index (BASFI) [17] was used to assess the functional capacity. The BASFI, BASDAI, and ASQoL questionnaires and the ASDAS index were previously translated and/or validated at our center [7, 18, 19]. Blood samples were taken to determine the ESR by the Westergren method. SASDAS was calculated by the simple linear addition of ASDAS which includes five components: patient global assessment (VAS 0 10 cm), back pain (BAS- DAI question no. 2, 0 10 cm), peripheral pain and swelling (BASDAI question no. 3, 0 10 cm), duration of morning stiffness (BASDAI question no. 6, 0 10 cm), and ESR in millimeters per hour, divided by 10 so as to make it equivalent to the other scale's components. For statistical analysis, descriptive statistics were performed. Correlation between ASDAS and other disease assessment measures was performed by Spearman's test. A multiple linear regression analysis was made using SAS- DAS as dependent variable to assess its main associated variables. Tolerance and variance inflator factor were included in the analysis. Continues variables were compared by ANOVA with Levene's test for homogeneity of variances and pos hoc analysis by Games Howell test. SASDAS cutoff values for different disease stages were analyzed using receiver operating characteristic (ROC) curves. A p value< 0.05 was considered significant. SPSS version 15 statistical package was used for all statistical analysis. Results We included 86 patients: 69 (80.2 %) were men with a median age of 46 years (interquartile range (IQR) 32 58) and a median disease duration of 19 years (IQR 13 31). SASDAS showed an excellent correlation with the ASDAS (r00.93; Fig. 1). SASDAS also showed a good correlation with other classical measures such as global pain and nocturnal pain, BASFI, and BASDAI (Table 1). In multiple linear regression model using SASDAS as dependent variable, variables significantly associated with SASDAS were BASFI and global pain. Age, disease duration, and gender did not show any effect and seem not have any influence on SASDAS values (Table 2). Using the ASDAS cut-off values suggested by ASAS, we divided our group of patients according to those categories. Using ROC curves and those preset cut-off values, we investigated the corresponding cut-off points for the SAS- DAS. Sensitivity and specificity for the new SASDAS cutoffs were determined. The corresponding cut-off values for SASDAS were as follows: inactive disease from 0 to 7.8, moderate disease activity from 7.9 to 13.8, high disease activity from 13.9 to 27.6, and very high activity above Cut-off values showed a high discriminative capacity with 82 % sensitivity and 99 % specificity to differentiate inactive disease from the moderate activity, 90 % sensitivity and 99 % specificity to differentiate moderate activity from high activity, and 93 % sensitivity and 100 % specificity to differentiate high activity from very high activity. When the distribution of BASDAI was analyzed in relation to different SASDAS cut-off points, an upward distribution with a significant difference among the disease stages was observed (Fig. 2).

3 Fig. 1 Correlation between SASDAS and ASDAS 6.00 Spearman Rho: 0.93 ASDAS SIMPLIFIED ASDAS Discussion Main symptoms in AS are pain, stiffness, reduction of spinal mobility, and fatigue. Inflammatory symptoms as well as structural damage generate functional limitations, which affect patients' quality of life. In a study performed at our unit, functional disability correlated positively with disease activity, depression, fatigue, and quality of life and negatively with level of education [7]. Several studies have shown that disease activity correlates with functional capacity and high disease activity is the main cause of functional deterioration in patient with AS. These data show the importance of controlling disease activity in order to ensure an adequate quality of life in the future. BASDAI and ASDAS are the tools to monitor disease activity in patient with AS. Table 1 Correlation of the SASDAS with measures of disease assessment Variables r p BASDAI BASFI Global pain (VAS) Nocturnal pain (VAS) ASQoL BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, VAS Visual Analogue Scale, ASQoL Ankylosing Spondylitis Quality of Life The BASDAI is a self-administered questionnaire and reflects the disease activity. It takes into account the patient vision and is a very useful to measure disease activity in axial spondyloarthritis. The ASAS group developed a composite index, ASDAS, in order to get a more objective measure, including a lab parameter. ASDAS, recently developed, showed that it is a reliable and reproducible, and in accordance with some authors, it would be better than the BASDAI [9 11]. There are two versions: ASDAS-PCR and ASDAS- ESR. Pedersen et al. [10] showed that ASDAS-PCR has higher correlation with the physician and patient global assessment than the BASDAI. In another study, Nas et al. [11] showed that ASDAS-PCR and ASDAS-ESR had Table 2 Multiple linear regression model Variables r standardized coefficient Beta t Significance ASQoL BASFI Global pain (VAS) Age Disease duration Gender Association of SASDAS with different variables of the disease. Dependent variable: SASDAS ASQoL Ankylosing Spondylitis Quality of Life, BASFI Bath Ankylosing Spondylitis Functional Index, VAS Visual Analogue Scale

4 Fig. 2 Distribution of BASDAI as regards different SASDAS cut-off points ANOVA (GAMES-HOWELL) p= better discrimination between high and low activity than BASDAI and acute phase reactants. Others studies found that ASDAS was well correlated with patient's and physician's assessment but was similar to BASDAI [20 22]. We believe that a composite index as ASDAS can reflect and include the different aspects of disease activity. However, the ASDAS presents a composite formula which requires, for its calculation, the use of a scientific calculator or Internet access. For this reason, although we believe in the importance of ASDAS and its excellent correlation with measures of disease activity, given the complexity of its formula, we have retained the five items proposed by ASAS for the formulation of ASDAS but we developed our simplified version. Currently, there are no simplified indexes to follow-up patient with AS. Nevertheless, for measuring disease activity in rheumatoid arthritis patients, several composite indexes which can be simply calculated were developed such as SDAI, Clinical Disease Activity Index, and Indice de Actividad Simplificado [12, 23, 24]. These indexes exhibited an excellent correlation with DAS28 and they have the advantage of not requiring a calculator. This simplified version of the ASDAS is the first simplified composite index for AS and has shown an excellent correlation with ASDAS and other measures of disease activity such as BASDAI and VAS for pain. Regression analysis confirmed the association with disease activity measures and also showed that SASDAS has not been influenced by sex, age, or disease duration. Our study has some limitations. The number of patients included in our study is not large enough so that it will be tested in a larger group of patients and validated in other cohorts. ASAS's recommended formula is ASDAS-PCR and they take ASDAS-ESR as a second option. We decided to simplify the ASDAS-ESR formula in our study. We understand that this would be a minor problem based on thevalidityofbothversions.themainreasonforthis decision was economics; ESR is 10 times cheaper than PCR. Cut-off values for ASDAS were developed by an expert opinion and clinical trials, so we decided to extrapolate these values which showed excellent sensitivity and specificity [12]. However, it would be desirable to test the cut-off values in a larger group of patients including expert opinion and other measures of disease activity. In the same way, sensitivity to change has not been tested in this study and it should be tested in the future. Summing up, the results of our study show that SASDAS is a simple and practical tool to assess disease activity in patient with AS and it can be easily used in clinical practice. Key messages 1. A stringent monitoring of disease activity is essential in patients with ankylosing spondylitis. 2. ASDAS has proved to be a reliable tool to measure disease activity in patients with ankylosing spondylitis. 3. A simplified version of ASDAS is a practical tool to measure disease activity in AS patients and it can be easily to use in clinical practice.

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