The Prevalence of MRI-Defined Sacroiliitis and Classification of Spondyloarthritis in Patients with Acute Anterior Uveitis: A Longitudinal Single-Centre Cohort Study

Background: Acute anterior uveitis (AAU) is a relatively common extra-musculoskeletal manifestation of axial spondyloarthritis (axSpA); however, data on the prevalence of active sacroiliitis in patients with AAU are limited. Methods: 102 patients with AAU and 39 healthy subjects (HS) underwent clinical assessment and sacroiliac joint MRI. Patients with absence of active sacroiliitis were reassessed after two years. International Spondyloarthritis Society (ASAS) classification criteria for axSpA (regardless of patient’s age) and expert opinion for definitive diagnosis of axSpA were applied. Results: Although chronic back pain was equally present in both groups, bone marrow edema (BME) in SIJ and BME highly suggestive of axSpA was found in 52 (51%) and in 33 (32%) patients with AAU compared with 11 (28%) and none in HS, respectively. Out of all AAU patients, 41 (40%) patients fulfilled the ASAS classification criteria for axSpA, and 29 (28%) patients were considered highly suggestive of axSpA based on clinical features. Two out of the 55 sacroiliitis-negative patients developed active sacroiliitis at the two-year follow-up. Conclusions: One-third of patients with AAU had active inflammation on SIJ MRI and clinical diagnosis of axSpA. Therefore, patients with AAU, especially those with chronic back pain, should be referred to a rheumatologist, and the examination should be repeated if a new feature of SpA appears.

HLA Allele Prevalence in Disease-Modifying Antirheumatic Drugs-Responsive Enthesitis and/or Arthritis Not Fulfilling ASAS Criteria: Comparison with Psoriatic and Undifferentiated Spondyloarthritis

Spondyloarthritis (SpA) is a group of inflammatory rheumatic diseases characterized by common clinical features, such as inflammatory enthesitis, arthritis and/or back pain. SpA is strongly associated with human leukocyte antigen (HLA) class I allotype B27. Ankylosing spondylitis has historically been the SpA subgroup with one of the strongest, best-proven associations with HLA-B27. The remaining SpA subgroups, namely psoriatic arthritis (PsA), inflammatory bowel diseases-associated arthritis/spondylitis, reactive arthritis, and undifferentiated SpA (uSpA), have also been associated with HLA allotypes other than HLA-B27. In this retrospective study, we analyzed the association between the HLA class I and II haplotypes and the susceptibility to enthesitis and/or arthritis (E/A). Special attention was paid to E/A responding to disease-modifying antirheumatic drugs (DMARDs) not fulfilling ASAS classification criteria (ASAS−), as compared to ASAS+ forms including PsA and uSpA. The whole E/A group showed significant independent associations with HLA-A28(68), B27, Cw3, Cw12, and DQ1; taken singly, PsA was associated with HLA-B27 and DQ1, uSpA with HLA-B16(38,39) and B27, and E/A ASAS− with HLA-A28(68), Cw8, and Cw12. This study identified novel risk HLA allotypes for different SpA subgroups in an Italian population. HLA typing could aid the diagnosis and treatment of E/A subgroups, including DMARDS-responsive forms not fulfilling ASAS classification criteria.

Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol

Axial spondyloarthritis (SpA), is a major cause of chronic pain and disability that profoundly alters the quality of life of patients. Nearly half of patients with SpA usually develop drug resistance. Non-pharmacological treatments targeting inflammation are an attractive alternative to drug administration. Vagus nerve stimulation (VNS), by promoting a cholinergic anti-inflammatory reflex holds promise for treating inflammatory disease. Inflammatory reflex signaling, which is enhanced by electrically stimulating the vagus nerve, significantly reduces cytokine production and attenuates disease severity in animal models of endotoxemia, sepsis, colitis, and other preclinical models of inflammatory diseases. It has been proposed that vagal efferent fibers release acetylcholine (Ach), which can interact with α7-subunit-containing nicotinic receptors expressed by tissue macrophages and other immune cells to rapidly inhibit the synthesis/release of pro-inflammatory cytokines such as TNFα, IL-1β, IL-6, and IL-18. External vagal nerve stimulation devices are now available that do not require surgery nor implantation to non-invasively stimulate the vagal nerve. This double-blind randomized cross-over clinical trial aims to study the change in SpA disease activity, according to Assessment in Ankylosing Spondylitis 20 (ASAS20) definition, after 12 weeks of non-invasive VNS treatment vs. non-specific dummy stimulation (control group). One hundred and twenty adult patients with drug resistant SpA, meeting the ASAS classification criteria, will be included in the study. Patients will be randomized into two parallel groups according to a cross over design: either active VNS for 12 weeks, then dummy stimulation for 12 weeks, or dummy stimulation for 12 weeks, then active VNS for 12 weeks. The two stimulation periods will be separated by a 4 weeks wash-out period. A transcutaneous auricular vagus nerve stimulator Tens Eco Plus SCHWA MEDICOTM France will be used in this study. The active VNS stimulation will be applied in the cymba conchae of the left ear upon the auricular branch of the vagus nerve, using low intensity (2–5 mA), once à week, during 1 h. Dummy stimulation will be performed under the same conditions and parameters as active VNS stimulation, but at an irrelevant anatomical site: the left ear lobule. This multicenter study was registered on ClinicalTrials.gov: NCT04286373.

AB0835 IS BASELINE VITAMIN D STATUS RELATED WITH THE RESPONSE TO BDMARDS IN SPONDYLOARTHRITIS PATIENTS?

Background:Vitamin D is thought to have an important role in immune regulation and is being subject of research in several autoimmune diseases. Some data suggest that vitamin D deficiency is common in Spondyloarthritis (SpA) and may be associated with disease activity and structural damage.Objectives:To evaluate if there is a relation between baseline vitamin D status and the response to biologic disease-modifying antirheumatic drugs (bDMARDs) in a SpA monocentric cohort.Methods:Retrospective study including all the SpA patients (ASAS classification criteria) followed at our Rheumatology Department, registered in the national database and treated with bDMARD between June 2008 and July 2020. Demographic, clinical and laboratorial data (including 25-hydroxyvitamin D [25-OHvitD]) at baseline and disease activity measures at 6 and 12 months of treatment with the first bDMARD were collected. Correlations between variables were evaluated by Spearman rank test, Mann-Whitney U test was used to the comparison analysis between groups and univariate logistic regression was used in the prediction analysis.Results:A total of 195 SpA patients were included: 103 (52.8%) females, 47 (24.1%) smokers and 91 (46.7%) HLA-B27 positive; 139 (71.3%) had Ankylosing Spondylitis, 18 (9.2%) had Inflammatory Bowel Disease Associated SpA and 38 (19.5%) had Undifferentiated SpA. At the time of the first bDMARD, the mean age was 43.5 years (±9.6) and the median disease duration was 12.4 years (0.7-52.7). The mean ASDAS-CPR (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) was 3.9 (±0.8) and, in addition, 61 (31.3%) patients had 25-OHvitD levels below 30 ng/mL and 12 (6.2%) had 25-OHvitD levels below 20 ng/mL. Fifty-three patients (27.2%) were taking NSAIDs (nonsteroidal anti-inflammatory drugs), 77 (39.5%) were under csDMARDs (conventional synthetic disease-modifying antirheumatic drugs). Adalimumab (56%) and golimumab (33.3%) were the most frequently initiated bDMARDs in the first line.There were no statistically significant correlations between baseline 25-OHvitD levels and ASDAS-CRP at 6 (r=0.031; p=0.714) and 12 months (r=0.035; p=0.672) of bDMARD.In the subgroup analysis: there were no statistically significant differences in the response to bDMARD at 6 and 12 months evaluated by ASDAS response and ASAS 20, 40 and 70 responses according to the baseline 25-OHvitD levels (25-OHvitD <20ng/mL vs ≥20ng/mL; 25-OHvitD <30ng/mL vs ≥30ng/mL); and there were no statistically significant differences in the baseline 25-OHvitD levels at baseline according to the response to bDMARD at 6 and 12 months of bDMARD (ASDAS: no response vs clinically important improvement or major improvement; ASAS 20: no response vs response).In the line of these previous results, baseline 25-OHvitD levels did not predict the ASDAS response at 6 (OR 0.97 [0.95-1.00], 95% CI) or 12 (OR 0.98 [0.95-1.01], 95% CI) months of bDMARD.Conclusion:Despite some data that suggest that lower levels of 25-OHvitD may be associated with higher disease activity in SpA, our results failed to demonstrate that the baseline 25-OHvitD levels can be related or predict treatment response after 6 and/or 12 months of therapy with the first bDMARD in real-life SpA patients.Disclosure of Interests:None declared

POS1387 QUANTIFICATION OF BONE MARROW EDEMA BY MRI OF THE SACROILIAC JOINTS IN PATIENTS DIAGNOSED WITH AXIAL SPONDYLOARTHRITIS: RESULTS FROM THE ESPERANZA COHORT

Background:The present study analyzes the added value of quantification by MRI of SI joints by comparing it to the standard interpretation with ASAS criteria for the classification of patients with axSpA of recent onset and a six-year follow-up.Objectives:To evaluate if the quantification of bone marrow edema (BME) of the sacroiliac (SI) joints by magnetic resonance imaging (MRI) improves capacity for axial spondyloarthritis (axSpA) classification in comparison to the assessment of sacroiliitis by means of ASAS classification criteria.Methods:Prospective study from the ESPeranza cohort involving 66 subjects with an available MRI of the SI joints at baseline. This subgroup includes patients with axSpA (n=28), peripheral spondyloarthritis (n=10) and a group with other diagnoses that were not spondyloarthritis (n=28). Measures of diagnostic usefulness (area under the curve (AUC), sensitivity, specificity, Youden’s J statistic, LR+ and LR-) were calculated for MRI of the SI joints according to ASAS criteria and for MRI quantified by means of SCAISS (Spanish tool for semi-automatic quantification of sacroiliac inflammation by MRI in spondyloarthritis). This analysis was stratified in patients who were HLA-B27 positive and negative.Results:Out of a total of 66 MRI of the SI joints, 20 (30.3%) were positive according to ASAS criteria. Out of these 20 subjects, 18 patients with final diagnosis of axSpA had a positive MRI, and 2 patients did not have axSpA. Out of the 66 patients of the cohort, 23 (34.8%) patients were HLA-B27 positive and 42 (63,6%) were negative. AUC value with bone marrow edema (BME) quantification was 0.919 (CI95% 0.799-1) for HLA-B27 positive patients and 0.884 (CI95% 0.764-1) for HLA-B27 negative patients. A SCAISS cutoff point of 80 units obtained a specificity of 94.4% and LR+ 7.5, while assessment by ASAS criteria showed a specificity value of 90% and LR+ 6.4.Conclusion:For patients with suspected axSpA, quantification of BME improves the predictive capacity of MRI of the SI joints, for both HLA-B27 positive and negative patients.Disclosure of Interests:None declared

POS1411 EARLY IDENTIFICATION OF AXIAL SPONDYLOARTHRITIS IN A MULTI-ETHNIC ASIAN POPULATION

Background:To facilitate earlier diagnosis of spondyloarthritis (SpA), we have previously cross-culturally adapted a self-administered screening questionnaire.Objectives:We aimed to improve the sensitivity of this questionnaire as a screening tool by comparing various scoring methods.Methods:Subjects newly referred to a rheumatology clinic self-administered the questionnaire before seeing a rheumatologist. Identification of axial SpA by the questionnaire using original scoring (Method A) and scoring based on Assessment of SpondyloArthritis International Society (ASAS) inflammatory back pain (IBP) criteria (Method B), ASAS referral criteria (Method C), ASAS classification criteria (Method D) and a combination of ASAS referral and classification criteria (Method E) were compared to classification by the ASAS classification criteria and diagnosis by rheumatologist. Since Methods B-E were based on SpA features, we compared self-reported vs rheumatologist-documented features in subjects with axial SpA.Results:Of 1418 subjects (age: 54 ± 14 years, female: 73%), 39 were classified as axial SpA cases by classification criteria. Methods A-E yielded sensitivities of 39%, 72%, 67%, 49% and 85%, respectively, among patients newly referred to the rheumatology clinic (Table 1). Rheumatologist-documented clinical SpA features exceeded self-report for IBP (62 vs 44%) and uveitis (15 vs 5%). The reverse was true for arthritis (21 vs 80%), enthesitis (28 vs 33%), dactylitis (3 vs 18%), good response to NSAIDs (33 vs 41%) and family history for SpA (5 vs 10%).Table 1.Performance of the five scoring methods for the cross-culturally adapted Hamilton axial SpA questionnaire.Scoring methodSensitivity(95% confidence interval)Specificity(95% confidence interval)Positive predictive value(95% confidence interval)Negative predictive value(95% confidence interval)Method A38.5(23.4 – 55.4)93.7(92.3 – 94.9)14.7(8.5 – 23.1)98.2(97.3 – 98.8)Method B71.8(55.1 – 85.0)73.1(70.7 – 75.4)7.0(4.7 – 10.0)98.9(98.1 – 99.5)Method C66.7(49.8 – 80.9)77.8(75.5 – 80.0)7.8(5.2 – 11.3)98.8(98.0 – 99.4)Method D48.7(32.4 – 65.2)74.9(72.5 – 77.2)5.2(3.2 – 8.0)98.1(97.1 – 98.8)Method E84.6(69.5 – 94.1)37.2(34.6 – 39.8)3.7(2.5 – 5.1)98.8(97.5 – 99.6)Method A: the original scoring defined by the questionnaire developers; Method B: a scoring based on the ASAS IBP criteria; Method C: a scoring based on the ASAS referral criteria; Method D: a scoring based on the ASAS classification criteria for axial and peripheral SpA; Method E: a scoring based on a combination of the ASAS referral and classification criteria.Conclusion:A self-administered questionnaire scored based on a combination of ASAS referral and classification criteria achieved high sensitivity in identifying axial SpA in subjects referred to a rheumatology clinic. This supports its evaluation as a screening tool for axial SpA in the general population.References:[1]Xiang L, Teo EPS, Low AHL, Leung YY, Fong W, Xin X, et al. Cross-cultural adaptation of the Hamilton axial spondyloarthritis questionnaire and development of a Chinese version in a multi-ethnic Asian population. Int J Rheum Dis. 2019;22(9):1652-60.[2]Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Annals of the rheumatic diseases. 2009;68 Suppl 2:ii1-44.[3]Poddubnyy D, van Tubergen A, Landewe R, Sieper J, van der Heijde D. Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Annals of the rheumatic diseases. 2015;74(8):1483-7.[4]Rudwaleit M, van der Heijde D, Landewe R, Akkoc N, Brandt J, Chou CT, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Annals of the rheumatic diseases. 2011;70(1):25-31.Acknowledgements:This work was supported by a Health Services Research Grant (HSRG) from the Singapore Ministry of Health National Medical Research Council [grant number: NMRC/HSRG/0075/2017].Disclosure of Interests:None declared

Exploring the Prevalence and Factors Associated With Fatigue in Axial Spondyloarthritis in an Asian Cohort in Singapore

Aim: To evaluate the prevalence of fatigue and the factors associated with fatigue among patients with axial spondyloarthritis (axSpA) within an Asian population.Method: We used the baseline data from a clinic registry in a tertiary referral center. All patients fulfilled the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA. Severe fatigue was defined as Bath Ankylosing Spondylitis Disease Activity Index-fatigue (BASDAI-fatigue) ≥5/10 and vitality domain of Short Form-36 Health Survey (SF-36 VT) ≤10th percentile of the general population.Results: We included 262 consecutive patients with axSpA (79% men, 82.4% Chinese). The mean (standard deviation, SD) age and duration of disease were 41.7 (13.7) and 10.1 (8.3) years, respectively. 145 (55.3%) and 52 (31.1%) patients reported severe fatigue by the BASDAI-fatigue and SF-36 VT criteria, respectively. Patients with severe fatigue had worse scores across all disease activity assessments and disease impact measures compared to those without severe fatigue. Using principal component analyses, disease activity and impact were associated with BASDAI-fatigue, while disease activity and impact, and disease chronicity were associated with SF-36 VT. In the univariable analyses, all disease activity assessments and disease impact measures correlated with both BASDAI-fatigue and SF-36 VT. In the multivariable analyses, BASDAI-axial pain, BASFI, BAS-G, and ethnicity were associated with BASDAI-fatigue, while ASQoL and BASDAI-morning stiffness were associated with SF-36 VT.Conclusion: Fatigue is prevalent amongst patients with axSpA in Asia and is associated with disease activity, disease impact as well as patient related factors.

The role of lymphocyte-monocyte ratio on axial spondyloarthritis diagnosis and sacroiliitis staging

Background: Axial spondyloarthritis (axial SpA) is a chronic inflammatory disorder could lead to disability due to the failure of timely treatment. The role of lymphocyte-to-monocyte ratio (LMR) in axial SpA remains unclear. The aim of this study was to investigate the role of LMR in axial SpA diagnosis, disease activity classification and sacroiliitis staging.Methods: Seventy-eight axial SpA patients [51males and 27 females; mean age 41.0 (29–52) years] and 78 healthy controls (HCs) [55males and 23 females; mean age 40 (30-53) years] were enrolled in this study. The diagnosis of axial SpA was performed according to the New York criteria or the Assessment of Spondyloarthritis international Society (ASAS) classification criteria, whereas the staging of sacroiliitis in axial SpA patients was determined by X-ray examination. Comparisons of LMR levels between groups were performed using t test. Pearson or Spearman correlation analysis were used to assess correlations between LMR and other indicators. Receiver operating characteristic (ROC) curves were used to determine the role of LMR in the diagnosis of axial SpA.Results: Higher neutrophil-to-lymphocyte ratio(NLR), red blood cell distribution width(RDW), platelet-to-lymphocyte ratio(PLR), mean platelet volume(MPV), erythrocyte sedimentation rate (ESR), and C-reactive protein(CRP) levels and lower red blood cell (RBC), hemoglobin (Hb), Hematocrit (Hct), LMR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin/globulin (A/G) levels were noted in axial SpA patients compared to HCs. Positive correlations were observed between LMR and RBC, Hb, Hct and A/G, whereas negative correlations were found between LMR and NLR, PLR, AST, and TBIL (P< 0.05). ROC curves showed that the area under the curve (AUC) for LMR in the diagnosis of ankylosing spondylitis was 0.803 (95% CI =0.734-0.872) with a sensitivity and specificity of 62.8% and 87.2%, respectively, and the AUC (95% CI) for the combination of ESR, CRP and LMR was 0.975 (0.948-1.000) with a sensitivity and specificity of 94.9% and 97.4%, respectively. LMR levels were lower (P<0.05) and significant differences in LMR values were observed among different stages (P<0.05).Conclusions: Our study suggested that LMR might be an important inflammatory marker to identify axial SpA and assess disease activity and X-ray stage of sacroiliitis.

The role of lymphocyte-monocyte ratio on axial spondyloarthritis diagnosis and sacroiliitis staging

Background Axial spondyloarthritis (axial SpA) is a chronic inflammatory disorder could lead to disability due to the failure of timely treatment. The role of lymphocyte-to-monocyte ratio (LMR) in axial SpA remains unclear. The aim of this study was to investigate the role of LMR in axial SpA diagnosis, disease activity classification and sacroiliitis staging. Methods Seventy-eight axial SpA patients [51males and 27 females; mean age 41.0 (29–52) years] and 78 healthy controls (HCs) [55males and 23 females; mean age 40 (30–53) years] were enrolled in this study. The diagnosis of axial SpA was performed according to the New York criteria or the Assessment of Spondyloarthritis international Society (ASAS) classification criteria, whereas the staging of sacroiliitis in axial SpA patients was determined by X-ray examination. Comparisons of LMR levels between groups were performed using t test. Pearson or Spearman correlation analysis were used to assess correlations between LMR and other indicators. Receiver operating characteristic (ROC) curves were used to determine the role of LMR in the diagnosis of axial SpA. Results Higher neutrophil-to-lymphocyte ratio(NLR), red blood cell distribution width(RDW), platelet-to-lymphocyte ratio(PLR), mean platelet volume(MPV), erythrocyte sedimentation rate (ESR), and C-reactive protein(CRP) levels and lower red blood cell (RBC), hemoglobin (Hb), Hematocrit (Hct), LMR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin/globulin (A/G) levels were noted in axial SpA patients compared to HCs. Positive correlations were observed between LMR and RBC, Hb, Hct and A/G, whereas negative correlations were found between LMR and NLR, PLR, AST, and TBIL (P < 0.05). ROC curves showed that the area under the curve (AUC) for LMR in the diagnosis of ankylosing spondylitis was 0.803 (95% CI = 0.734–0.872) with a sensitivity and specificity of 62.8 and 87.2%, respectively, and the AUC (95% CI) for the combination of ESR, CRP and LMR was 0.975 (0.948–1.000) with a sensitivity and specificity of 94.9 and 97.4%, respectively. LMR levels were lower (P < 0.05) and significant differences in LMR values were observed among different stages (P < 0.05). Conclusions Our study suggested that LMR might be an important inflammatory marker to identify axial SpA and assess disease activity and X-ray stage of sacroiliitis.

The role of lymphocyte-monocyte ratio on axial spondyloarthritis diagnosis and sacroiliitis staging

Background: Axial spondyloarthritis (axial SpA)is a chronic inflammatory disorder involving the sacroiliac joints, that could lead to disability due to the failure of timely treatment. The lymphocyte-to-monocyte ratio (LMR) is an indicator of disease progression. However, its role in axial SpA remains unclear. The aim of this study was to investigate the role of LMR in axial SpA diagnosis, disease activity classification and sacroiliitis staging. Methods: Seventy-eight axial SpA patients and 78 healthy controls (HCs) were enrolled in this study. The diagnosis of axial SpA was performed according to the New York criteria or the Assessment of Spondyloarthritis international Society (ASAS) classification criteria, whereas the staging of sacroiliitis in axial SpA patients was determined by X-ray examination. Comparisons of LMR levels between groups were performed using t test. Pearson or Spearman correlation analysis were used to assess correlations between LMR and other indicators. Receiver operating characteristic (ROC) curves were used to determine the role of LMR in the diagnosis of axial SpA.Results: Higher neutrophil-to-lymphocyte ratio(NLR), red blood cell distribution width(RDW), platelet-to-lymphocyte ratio(PLR), mean platelet volume(MPV), erythrocyte sedimentation rate (ESR), and C-reactive protein(CRP) levels and lower red blood cell (RBC), hemoglobin (Hb), Hematocrit (Hct), LMR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin/globulin (A/G) levels were noted in axial SpA patients compared to HCs. Positive correlations were observed between LMR and RBC, Hb, Hct and A/G, whereas negative correlations were found between LMR and NLR, PLR, AST, and TBIL (P< 0.05). ROC curves showed that the area under the curve(AUC) for LMR in the diagnosis of ankylosing spondylitis was 0.803 (95% CI =0.734-0.872) with a sensitivity and specificity of 62.8% and 87.2%, respectively, and the AUC (95% CI) for the combination of ESR, CRP and LMR was 0.975 (0.948-1.000) with a sensitivity and specificity of 94.9% and 97.4%, respectively. LMR levels were lower (P<0.05) and significant differences in LMR values were observed among different stages (P<0.05). Conclusions: Our study suggested that LMR might be an important inflammatory marker to identify axial SpA and assess disease activity and X-ray stage of sacroiliitis.