A total of 151 consecutive patients of Chinese ethnicity were prospectively recruited from two rheumatology specialist clinics between May to December 2017 and subsequently reassessed at a follow-up of 6 months later (November 2017 to June 2018). All recruited patients fulfilled either the Assessment of Spondyloarthritis international Society (ASAS) axial SpA criteria (13, 14) or peripheral SpA criteria (15) for diagnosis. All recruited patients were 18 years old or above. Patients who did not give consent for participation, non-Chinese, illiterate and unable to comprehend the instruments were excluded. Subjects who consented were interviewed for a panel of sociodemographic and disease-associated parameters, disease activity and severity factors, and HRQoL scores that highlight the functional and mental health status. Both baseline and follow-up interviews were conducted in person at the consultation clinic. At the follow-up interview, subjects were assessed by the same research personnel for a reassessment of the same study questionnaires as well as the global rating of change scale. To provide good quality of psychometric evidence, sample size of at least 100 was recommended by Terwee et al(16). Ethics was approved by the local institutional review board. All methods were carried out in accordance with relevant guidelines and regulations.
Sociodemographic and disease-associated data
Patients’ smoking and drinking habits, education level, income and occupation were recorded. Disease-associated data including disease duration, presence of back pain and/or peripheral arthritis, dactylitis, enthesitis, and extra-articular manifestations such as uveitis, psoriasis, and IBD were collected. Baseline treatment including the use of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (cox-2) inhibitors, disease modifying anti-rheumatic drugs (DMARDs) and biologics and any subsequent change in treatment after 6 months were documented. Physical examination was performed to determine the number of tender joint count and swollen joint count, the dactylitis and enthesitis scores. Antero-posterior radiograph of the lumbosacral spine was utilized for grading of sacroiliitis according to the modified New York criteria(17) by a rheumatologist (HYC) who was blinded to the clinical data. Radiological sacroiliitis was graded as: 0, normal; 1, suspicious; 2, minimal sclerosis with some erosions; 3, erosion with widening of joint space and possible partial ankyloses; 4, complete ankyloses. Bilateral sacroiliitis of grade 2 or above, or unilateral sacroiliitis of grade 3 or above was defined as AS. Patients were treated by the attending rheumatologist according to their disease activity and severity.
Disease activity and severity scores
All recruited patients filled in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(18) and BASFI(19) to determine the disease activity and functional disability respectively. Spinal mobility was assessed clinically to determine the Bath Ankylosing Spondylitis Metrology Index (BASMI) score (20). The Bath Ankylosing Spondylitis Global Index (BASGI)(21) and C-reactive protein (CRP) were measured for calculation of the Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP)(22), which is a composite disease activity measure of SpA. Human leucocyte antigen (HLA) B27 status was also checked as a poor prognostic marker.
Functional and mental health status
The SF-36(23-25) was used for assessment of mental and physical health and as a comparable generic questionnaire marker of EQ-5D changes. Hospital Anxiety and Depression Scale (HADS)(26) is a fourteen-item scale with seven items each for anxiety and depression subscales. It has been validated in Chinese axial SpA patients and is found to useful in screening for depressive and anxiety disorders in SpA.(27)
The main study parameter was the EQ-5D which is a standardized measure of health status developed by the EuroQoL group that allows a generic assessment of health status for clinical and economic appraisal(10). It has been useful in assessing the HRQoL in patients with musculoskeletal problems.(28-32) It consists of a 2-page questionnaire, the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system is comprised of 5 domains, including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. There are 2 versions of EQ-5D, namely the EQ-5D-3 level (EQ-5D-3L) and the EQ-5D-5 level (EQ-5D-5L) versions. For the EQ-5D-3L, each domain will be scored by 3 levels (no problem, some problem and extreme problem). We utilized the EQ-5D-5L version for this study and each domain of this parameter was scored by 5 levels with 1 representing no problem and 5 representing extreme problem. Previous studies published by EuroQoL group have shown that the 5 level version could significantly increase reliability and sensitivity while maintaining the feasibility of the test and it could potentially reduce ceiling effects(10). The scores of the 5 domains are combined into a 5-digit number which is converted into a single index value. The EQ-VAS allows patients to self-report their own perceived quality of life from a scale of 0 (worst) to 100 (best). We applied Chinese-specific EQ-5D-5L value set ranging from -0.391 for the worst health status (‘55555’) to 1 for the best health status (‘11111’) to estimate EQ score.(33)
Generic and Clinical Anchors
It was necessary to include an external anchor to act as a reference for indicating patient improvement or deterioration. To test the responsiveness of EQ-5D, this anchor represented the patient-reported assessment of health change over time and thus indicate whom change in health occurred(34). The global rating of change (GRC) scale is a single-item outcome measure for independent scoring of self-perceived improvement in a patient retrospectively and has been used in musculoskeletal research(35). All subjects answered the question “Compared to the previous visit, how would you rate your overall health now?”.(35) The response scale was a seven-point Likert scale ranging from -3 to 3 corresponding to the ‘much worse’ to the ‘much better’ options with 0 for ‘no change’. Three groups were defined using this scale: ‘worse’ (-3 to -1), ‘unchanged’ (0) and ‘improved’ (1 to 3). Such re-grouping or categorization was applied in previous studies to evaluate responsiveness.(29, 36)
The GRC was a generic anchor used to test the overall patient improvement or deterioration. Clinical anchors were also applied namely BASDAI and ASDAS-CRP to assess the changes in disease activity. These differences were more representative of actual improvement or deterioration in the disease as compared to the GRC scale which may be subjected to mental and psychological influences.
Statistical analysis
Overall descriptive characteristics were reported with mean ± standard deviation (SD). Any differences between baseline and follow-up were compared using independent t-test and Chi-squared test where appropriate. The responsiveness of the EQ-5D was assessed using the effect size statistics. Differences between baseline and follow-up of the utility score was evaluated by standardized effect size (SES) and standardized response mean (SRM) separately for GRC, BASDAI and ASDAS-CRP. BASDAI of <4 is considered low disease activity and a BASDAI ≥4 represents high disease activity by expert consensus.(18) Change in disease activity either to the low disease activity group (improved) or high disease activity group (worsened) was studied. Those that stayed within their baseline groups at follow-up was considered “unchanged”. ASDAS-CRP is categorized as inactive disease (<1.3), moderate disease activity (1.3-<2.1), high disease activity (2.1-<3.5), and very high disease activity (>3.5). A change of 1.1 is considered as clinically significant change.(37) The SES and SRM results were interpreted as trivial for values <0.2, small for values ≥0.2 to <0.5, moderate for values ≥0.5 to <0.8, and large for values ≥0.8(38).
Spearman’s correlation was performed to assess the relationship between changes in EQ-5D scores with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ASDAS-CRP, ASDAS-ESR, BASDAI, BASFI, SF-36, and HADS. Spearman’s correlation was used because the data was not normally distributed as reviewed by the Shapiro-Wilk normality test. All statistical analyses were conducted using STATA version 13.0. A p-value of <0.05 was considered as statistically significant and 95% confidence intervals (CIs) were listed as appropriate.