ASAS-endorsed Disease Activity Score Research Articles

POS0369 ELEVATED EXPRESSION OF TIM-3 ON NEUTROPHILS CORRELATES WITH DISEASE ACTIVITY AND SEVERITY OF ANKYLOSING SPONDYLITIS

Background:Ankylosing spondylitis (AS) is a type of common, chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints, causing inflammatory low back pain and progressive spinal stiffness, over time some patients develop spinal immobility and ankylosis which can lead to a decrease in quality of life. The last few decades, evidence has clearly indicated that neutrophil also plays key roles in the progression of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear.Objectives:In this study, we investigated the expression of Tim3 on neutrophils in AS patients and explored the correlation between the level of Tim3-expressing neutrophils and the disease activity and severity of AS.Methods:Patients with AS were recruited from Guangdong Second Provincial General Hospital (n=62). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The mRNA expression of PD-1 and Tim-3 was determined by real-time PCR. The levels of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with the markers of inflammation such as ESR,CRP,WBC and neutrophil count(NE), as well as disease activity and severity of AS. The expression of Tim3 on neutrophils was monitored during the course of treatment (4 weeks).Results:The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). However, significant difference was observed in the frequency of PD-1-expressing neutrophils between AS patients and HC (Figure 1B). The expression analysis of Tim-3 mRNA, but not PD-1, confirmed the results obtained from flow cytometry (Figure 1C). The level of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1D). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS<1.3) (Figure 1E). As shown in Figure 1F, the frequency of Tim3-expressing neutrophils decreased after the treatment.Conclusion:Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients.

AB0693 TIM-3-EXPRESSING NEUTROPHILS AS A NOVEL INDICATOR TO ASSESS DISEASE ACTIVITY AND SEVERITY IN ANKYLOSING SPONDYLITIS

Background:Ankylosing spondylitis (AS) is a type of chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints. Many studies have shown that neutrophils play an important roles in the inflammatory process of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear.Objectives:In this study, we investigated the expression of Tim3 on neutrophils in AS patients and analyzed the correlation between the level of Tim3-expressing neutrophils and the disease activity of AS.Methods:AS Patients were recruited from Guangdong Second Provincial General Hospital (n=49). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The frequencies of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with markers of inflammation ESR and CRP, disease activity and severity of AS.Results:The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). The frequency of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1B). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS<1.3) (Figure 1C).Conclusion:Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients.

Evaluation of quality of life in patients with axial spondyloarthritis and its association with disease activity, functionality, mobility, and structural damage.

To evaluate quality of life (QoL) in patients with axial spondyloarthritis (axSpA) and its association with disease activity, functionality, structural damage, and spinal mobility, using patient-reported outcomes. This was an observational, cross-sectional, and single-center study in which 100 consecutive patients with axSpA were included. We obtained from all patients' sociodemographic data and values related to disease activity, functionality, structural damage, mobility, and quality of life. The Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) was considered as the primary outcome. Pearson r statistic, Student's T test, and univariate and multivariate linear regressions were performed to relate ASQoL with the studied covariates. Mean ASQoL score in all patients was 4.02 ± 2.81, with statistically significant differences between male and female (3.61 ± 2.80 vs. 4.83 ± 2.70). Patients with high disease activity (measured by the ASAS-endorsed Disease Activity Score, ASDAS > 2.1) showed higher mean score in ASQoL than those with low disease activity (ASDAS ≤ 2.1) (3.21 ± 0.74 vs. 1.43 ± 0.43, p < 0.001). ASQoL presented a significant linear correlation with BASDAI, BASFI, and ASDAS (r > 0.60). However, disease duration was not significantly correlated with ASQoL. Finally, the 68.9% of the ASQoL variability (R2 = 0.689) was determined by BASDAI, BASFI, and mSASSS, presenting mSASSS a negative regression coefficient (- 0.035). In our study, the impairment of QoL was mainly associated with disease activity (BASDAI) and worsening of functionality (BASFI). However, there is an inverse relationship between the worsening of QoL and structural damage. In addition, disease duration does not seem to influence the patient's welfare.

Vitamin D Deficiency and Sub-Clinical Osteomalacia in Axial Spondyloarthropathy

Objectives: The role of bone disease in spondyloarthropathy (SpA) remains of great interest with evidence of an increased risk of bone fragility and fracture. The effects of lifestyle factors such as sun light exposure and vitamin D deficiency on SpA remain uncertain. The study was to examine those factors on skeletal integrity in axial spondyloarthropathy (axSpA) patients associated with sub-clinical osteomalacia. Material and Methods: 95 axSpA patients and 74 healthy controls in the same season were enrolled. ASAS-endorsed disease activity score (ASDAS), 25-hydroxyvitamin D, parathyroid hormone (PTH), bone turnover biomarkers procollagen type 1 N-terminal peptide (PINP) and osteocalcin(OC), serum C-telopeptides of type I collagen (sCTX), serum alkaline phosphatase (sALP), adjusted calcium, C-reactive protein, bone minimal density (BMD) of total proximal femur and lumbar spine were measured. Questionnaires on daily sun exposure time and other factors were ascertained. Results: axSpA patients were with significantly decreased vitamin D and raised sALP levels than controls (p<0.001). 74% of axSpA patients had vitamin D deficiency. Their vitamin D levels were inversely related to the disease duration (r=-0.234, p<0.05) but positively to daily sunlight exposure time and calcium (r=0.064, p<0.001, respectively). axSpA patients had significantly higher bone turnover biomarkers sCTX and OC (p<0.05), and significantly lower femoral neck T and Z scores in BMD than controls (p=0.000). Conclusion: Vitamin D insufficiency exist in most (74%) of axSpA patients. axSpA patients exhibited significantly lower vitamin D and raised ALP levels, and with significantly higher bone turnover biomarkers and low BMD than controls, which indicated that subclinical biochemical osteomalacia associated with most axSpA patients.

AB0922 Disease activity assessment in ankylosing spondylitis: Basdai or asdas?

BackgroundRecently, a new index, the Ankylosing Spondylitis Disease activity Score (ASDAS), has been shown to be a validated and highly discriminatory instrument in assessing disease activity.ObjectivesTo evaluate the performance of...

SAT0263 Validity of ankylosing spondylitis disease activity score (ASDAS) in patients with early spondyloarthritis

BackgroundRecently, a Working Group of the SpondyloArtrhitis International Society (ASAS) has proposed a composite disease activity score, the Ankylosing Spondylitis Disease Activity Score (ASDAS), for patients with ankylosing spondylitis (AS),...

AB0891 Correlation of ASDAS and BASDAI with disease activity in axial spondyloarthritis

BackgroundThe Spondyloarthritis International Society (ASAS) published a new measurement tool to help in the assessment of disease activity in Ankylosing Spondylitis (AS) patients and as an instrument to assess treatment...

Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to anti-TNF therapy? A multicentre retrospective observational study.

IntroductionThe aim of this study was to evaluate, under real-life conditions, the safety and efficacy of tocilizumab in patients having failed anti-TNFα therapy for spondyloarthritis.MethodsFrench rheumatologists and internal-medicine practitioners registered on the Club Rhumatismes et Inflammations website were asked to report on patients given tocilizumab (4 or 8 mg/kg) to treat active disease meeting Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral spondyloarthritis, after anti-TNFα treatment failure. Safety and efficacy after 3 and 6 months were assessed retrospectively using standardised questionnaires.ResultsData were obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age, 42 years; disease duration, 11 years; HLA-B27-positive, 92.3%) and eight with peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10 years; HLA-B27-positive, 62.5%). No patients with axial disease had at least a 20 mm decrease in the BASDAI, nor a BASDAI50 response or major ASAS-endorsed disease activity score improvements after 3 or 6 months; an ASAS-endorsed disease activity score clinically important improvement was noted at month 3 in five of 13 patients and at month 6 in one of four patients. A good DAS28 response was achieved in four patients with peripheral disease, including one in EULAR remission at month 3. Four patients were still taking tocilizumab at month 6, including one in EULAR remission and one with a good DAS28 response. Tocilizumab was well tolerated, with no serious adverse events. Initially elevated acute-phase reactants declined during tocilizumab therapy.ConclusionIn patients having failed anti-TNFα therapy, tocilizumab decreased acute-phase reactants but failed to substantially improve axial spondyloarthritis and was inconsistently effective in peripheral spondyloarthritis.

The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a cross-sectional analysis

SummaryOsteoporosis is a well recognized complication of ankylosing spondylitis (AS). This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis, and that bone turnover markers (BTM) are valuable markers to detect bone loss in AS.IntroductionThe aim of this study was to elucidate the pathophysiology of AS-related osteoporosis by investigating the relation between bone mineral density (BMD), BTM, vitamin D, and clinical assessments of disease activity and physical function, as well as to identify parameters that are related to low BMD (osteopenia or osteoporosis) in AS patients with active disease.MethodsOne hundred twenty-eight consecutive Dutch AS outpatients were included in this cross-sectional study. Bath AS Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), C-reactive protein, ASAS-endorsed disease activity score (ASDAS), Bath AS Functional Index (BASFI), bone formation markers procollagen type 1 N-terminal peptide (PINP) and osteocalcin (OC), bone resorption marker serum C-telopeptides of type I collagen (sCTX), 25-hydroxyvitamin D (25OHvitD), lumbar spine and hip BMD, and vertebral fractures were assessed. Z-scores of BTM were calculated using matched 10-year cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover.ResultssCTX Z-score, OC Z-score, BASDAI, age, and gender were independently related to low BMD. In addition, PINP Z-score, ESR, 25OHvitD, age, and gender were independently related to sCTX and/or OC Z-score.ConclusionsThis study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis. Furthermore, sCTX and OC Z-scores seem to be valuable markers to detect bone loss in AS patients in daily clinical practice where BMD of the lumbar spine, measured by DXA, may be overestimated due to osteoproliferation in patients with advanced AS.

Critères de réponse dans les spondylarthropathies : définition d’un répondeur

Therapy upsets of the ten last years have made necessary a better assessment of spondylarthropathies. Since the appearance of anti-TNFα drugs, it became determinant to assess disease activity and therapeutic response, both in real life and studies. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is considered as the gold standard to assess disease activity for fifteen years. National and international recommendations use it to define the minimal disease activity required before the beginning of anti-TNFα drugs. Moreover, therapeutic response is defined by a variation of at least 20 mm by 100 or at least 50% of its initial value. Other response criteria as Assessment of SpondylArthritis international Society (ASAS) criteria have been created; initially ASAS 20 have been developed from NSAID studies, but ASAS 40 and 70 are more conformed to the frequency and the amplitude of response observed with anti-TNFα. Partial remission, as defined by ASAS group, charge even more and more interest and signification with these new treatments. Recently, a new disease activity score called ASAS-endorsed disease activity score (ASDAS) have been developed, with the same process than the Disease Activity Score (DAS) in rheumatoid arthritis. Contrary to BASDAI, it takes into account the biological inflammatory parameters. It should shortly permit to define reliable disease activity levels, and then, from variation of these levels, response criteria in the manner of European League Against Rheumatism (EULAR) response in rheumatoid arthritis.

Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis

Objectives:To develop a new index for disease activity in ankylosing spondylitis (ASDAS) that is truthful, discriminative and feasible, and includes domains/items that are considered relevant by patients and doctors.Methods:Eleven candidate...