SpondyloArthritis International Society Classification Criteria Research Articles

Absence of overexpression of KIR3DL2 on CD4+ T cells and NK cells in patients with axial spondyloarthritis.

Dear Editor, Chan et al. described an overexpression of KIR3DL2, a receptor for HLA-B27 homodimer, on NK cells and CD4+ T cells in patients with axial SpA (axSpA) [1, 2]. HLA-B27:05 expressing cells have also been shown to promote KIR3DL2+ NK cells, with more NK cells and CD4+ T cells expressing KIR3DL2 in patients with axSpA [3]. However the overexpression of KIR3DL2 was not confirmed in another population of patients with active axSpA [4]. All these studies were conducted in patients carrying the HLA-B27 antigen. We aimed to assess the expression of KIR3DL2 in patients with axSpA, according to the presence or not of HLA B27. We included 20 patients with axSpA [16 with AS and 4 with non-radiographic axSpA (nr-axSpA)] fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria [5] and 5 healthy controls. Stratification according to the presence or not of HLA-B27 was applied. The axSpA main characteristics were: 11 HLA-B27+, 9 HLA-B27-, 14 males, mean disease duration 15.2 years and mean BASDAI of 4.7/10; all were synthetic and biologic DMARD naïve. We analysed by flow cytometry whole blood and peripheral blood mononuclear cell samples using fluorescent antibodies against CD45, CD14, CD3, CD19, CD4, CD8, gamma-delta-TCR, CD56, CD16, CD45RA, CXCR3, CCR6, KIR3DL1, KIR3DL2, IL-17A, IL-22, IL-2 and IFN-gamma. Positivity thresholds were set using control isotypes. Overnight pharmacological stimulation was performed with PMA/Ionomycin. All statistical analyses were performed using Graph Pad Prism (GraphPad Software, San Diego, CA, USA). Paired data were analysed with Wilcoxon test, and unpaired data with Mann–Whitney test. P-values <0.05 were considered to be significant. The study was approved by local ethics committee and conducted in accordance with the Declaration of Helsinki.

Anti-CD74 IgA antibodies show diagnostic potential for axial spondyloarthritis but are not associated with microscopic gut inflammation.

Gut inflammation commonly occurs in axial SpA (axSpA), and is linked to disease activity and outcome. Given the role of IgA in mucosal immunity, we explored the association between anti-CD74 IgA antibodies, gut inflammation and axSpA. Anti-CD74 IgA was measured by ELISA in serum samples of axSpA patients, fulfilling the 2009 Assessment of SpondyloArthritis international Society classification criteria. A group of fibromyalgia (FM) and RA patients served as non-inflammatory and inflammatory controls. Newly diagnosed axSpA patients underwent ileocolonoscopy; mucosal biopsies were histopathologically assessed as normal, acute or chronically inflamed. Optimal anti-CD74 IgA cut-off values were determined with a receiver operating characteristics curve. axSpA patients (n = 281) showed higher anti-CD74 IgA levels [mean (s.d.) 18.8 (12.4) U/ml] compared with 100 FM patients [10.9 (5.0) U/ml, P < 0.001] and 34 RA patients [13.7 (9.6) U/ml, P = 0.02]. The area under the receiver operating characteristics curve for diagnosis (axSpA vs FM) was 0.70, providing a sensitivity of 60% and specificity of 87% (cut-off 15 U/ml). Antibody concentrations were not significantly different between axSpA patients with (n = 40) and without (n = 69) gut inflammation (P = 0.83), yielding an area under the receiver operating characteristics curve of 0.51. Anti-CD74 IgA levels were not associated with degree of bone marrow oedema on MRI of the sacroiliac joints, CRP or any other disease-specific feature such as the use of NSAIDs or biological treatment. Serum anti-CD74 IgA is a potentially useful diagnostic biomarker for axSpA. However, antibody levels do not correlate with any phenotypical feature, including microscopic gut inflammation, suggesting this to be a disease-specific rather than an inflammatory marker.

Predictors of not Achieving Remission or Low Disease Activity in Axial Spondyloarthritis Patients from Middle Eastern Countries: A Prospective, Multicenter, Real-world Study.

ObjectivesWe sought to identify the predictors of not achieving remission or low disease activity (LDA) among axial spondyloarthritis (SpA) patients in four Middle Eastern countries.MethodsIn this multicenter prospective real-world study, adult patients with axial SpA diagnosed clinically during January–June 2019, and who met the Assessment of SpondyloArthritis International Society classification criteria for axial SpA, were enrolled from the participating centers of four countries—Lebanon, Oman, Qatar, and the UAE. Patient demographics, disease history, comorbidities, treatment, and compliance data were obtained at baseline. The primary outcome was to determine the percentage of patients who did not achieve the clinical target of remission or LDA as indicated by Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) < 2.1 after a three-month follow-up period. Secondary outcomes were assessing the demographic and clinical characteristics of ‘achievers’ and ‘non-achievers’ and to study the predictors of ASDAS-CRP ≥ 2.1 in different clinical subsets.ResultsThe participants were 309 patients of both sexes, with a median age of 43 years. Women had a slight majority (53.7%). At the end of the study, 72.2% of patients achieved the clinical target of ASDAS-CRP < 2.1. Non-achievers were significantly more likely to have enthesitis, positive human leukocyte antigen B 27 status, psoriasis, peripheral involvement, fibromyalgia, and a lower score on Compliance Questionnaire for Rheumatology (CQR). Multiple regression analysis showed that low CQR score, enthesitis, psoriasis, and family history of SpA were independent predictors of ASDAS-CRP ≥ 2.1.ConclusionsThis real-world study suggests that low compliance, positive human leukocyte antigen B 27 status, peripheral involvement, and presence of enthesitis, psoriasis, and fibromyalgia are predictors of not achieving remission or LDA in axial SpA patients.

OP0149 RADIOGRAPHIC PROGRESSION FROM NON-RADIOGRAPHIC TO RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: RESULTS FROM A 5-YEAR MULTICOUNTRY PROSPECTIVE OBSERVATIONAL STUDY

BackgroundPatients (pts) with axial spondyloarthritis (axSpA) are classified into radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) based on the presence or absence of radiographic sacroiliitis. Approximately 20% to 80% of newly diagnosed axSpA pts have nr-axSpA and 8% to 40% progress to r-axSpA over the next 2 to 10 years.ObjectivesTo evaluate progression from nr-axSpA to r-axSpA over 5 years in a prospective multicentre cohort.MethodsPROOF was a global, real-world, prospective, observational study conducted in rheumatology clinical practices in 29 countries across 6 different geographic regions.1 The study enrolled adults with chronic back pain for ≥3 months and onset before 45 years of age. This analysis included pts diagnosed with axSpA who also fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA. Study visits occurred at baseline (BL) and yearly thereafter. Baseline and follow-up radiographs of sacroiliac joints (SIJ) were evaluated for pts with initial nr-axSpA diagnosis independently by 2 central readers according to the modified New York criteria. In the case of disagreement on the classification (nr- or r-axSpA), images were adjudicated by a third reader. Radiographic progression from nr-axSpA to r-axSpA over 5 years was evaluated by Kaplan-Meier analysis. Cox proportional hazards regression analyses for time to radiographic progression from nr-axSpA to r-axSpA were conducted. For model 1, ‘imaging arm vs clinical arm’ was used as an independent variable, and for model 2, ‘active inflammation on magnetic resonance imaging highly suggestive of sacroiliitis associated with SpA’ was used. Further, potential predictive factors included in the models were age, gender, back pain duration, number of SpA parameters, smoking status, CRP, good response to NSAIDs, HLA-B27 status, and current use of NSAIDs and TNF inhibitors.ResultsAmong 2633 enrolled pts, 2165 (82%) were diagnosed with axSpA and fulfilled the ASAS classification criteria. Among these, 1612 (74%) were classified as having r-axSpA (1050 [65%]) or nr-axSpA (562 [35%]) by central reading. The majority of nr-axSpA pts (77%) fulfilled the ASAS classification criteria due to positive findings on imaging (plus ≥1 SpA feature) and 23% were classified according to the clinical arm. A total of 246 nr-axSpA pts who had ≥1 follow-up SIJ radiograph were included in this analysis. Among these 246 pts, progression from initial nr-axSpA to r-axSpA at any of the follow-up visits was observed in 40 pts (16%) over 5 years. Mean time to radiographic progression was 2.4 years (ranging from 0.9 to 5.1 years) in descriptive analysis (Kaplan-Meier curve shown in Figure 1). In model 1 of the Cox regression analysis, male gender (hazard ratio [HR]: 3.16 [95% CI: 1.22–8.17]; P=0.0174), fulfilment of the imaging arm (HR: 6.64 [1.37–32.25]; P=0.0188), and good response to NSAIDs, (HR: 4.66 [1.23–17.71]; P=0.0237), were significantly associated with progression to r-axSpA (Figure 1). In model 2, HLA-B27 positivity showed a significant association with progression (HR: 3.99 [1.10–14.49]; P=0.0353; Figure 1).ConclusionIn this study, 16% of nr-axSpA pts progressed to r-axSpA within 5 years. The mean time to disease progression was 2.4 years. Predictors of radiographic progression were male gender, good response to NSAIDs, and fulfilment of the imaging arm as well as HLA-B27 positivity.

Prevalence and risk factors for uveitis in spondyloarthritis.

To determine the prevalence and risk factors for uveitis in spondyloarthritis (SpA) patients. A total of 225 patients who fulfilled Assessment of Spondyloarthritis International Society classification criteria for axial and peripheral SpA were enrolled. The diagnosis of uveitis was confirmed by an ophthalmologist. From medical records and from clinical evaluation associated information like disease duration, and human leukocyte antigen B27 was collected. Relevant laboratory tests were done and disease severity was assessed using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score - erythrocyte sedimentation rate and C-reactive protein. Characteristics of uveitis positive and uveitis negative groups were compared. Multivariate logistic regression analysis was done for the risk factors, and P values <.05 were considered significant. Prevalence of uveitis was 18.7%. The disease duration was 9.3±7years and 5.4±4.5years in uveitis and no uveitis groups respectively (P≤.001). Family history of SpA was positive in 45.2% in the uveitis group (P≤.001). The frequency of axial SpA was 92.9% and 73.8% in the uveitis and no uveitis groups respectively (P≤.008). The mean BASDAI was 2.4±1.9 and 3.3±2.8 in uveitis and no uveitis groups respectively (P=.050). In multivariate logistic regression analysis, among the selected variables, family history of SpA (odds ratio [OR] =3.697; 95% CI =1.616-8.457; P=.002) and duration of disease (OR =1.089; 95% CI =1.004-1.181; P=.039) were independently associated with the occurrence of uveitis. The prevalence of uveitis was 18.7%. The family history and the disease duration of SpA were independently associated with uveitis.

Factors Associated With Diagnostic Delay of Axial Spondyloarthritis in Colombian Patients.

The diagnostic delay of axial spondyloarthritis (axSpA) is globally reported to be between 3 and 11 years. Early diagnosis and treatment have long-term benefits for patients and the health care system. Several international studies have evaluated some factors associated with diagnostic delay, but there are no known studies in the Colombian population. This study assesses the factors associated with diagnostic delay of axSpA in a rheumatology center in Bogota, Colombia. This monocentric analytical cross-sectional study was done in a specialized rheumatology center. Patients who fulfilled the 2009 Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axSpA were included. Information was obtained from medical records and a phone call. Bivariate and multivariate analyses were done to assess the associated factors with diagnostic delay. One hundred one patients were included, 54 were women (53.5%). The median diagnostic delay was 2 years (interquartile range, 1-7). The bivariate analysis showed that a younger age at diagnosis (p = 0.042) and previous diagnosis of lumbar degenerative disease (p = 0.029) were associated with a longer diagnostic delay. The logistical regression showed that previous lumbar degenerative disc disease (odds ratio, 2.8; 95% confidence interval, 1.09-7.53) and fibromyalgia (odds ratio, 4.0; 95% confidence interval, 1.2-13.1) diagnosis were both associated with a longer diagnostic delay. Factors associated with a longer diagnostic delay were previous diagnosis of lumbar degenerative disc disease and fibromyalgia. Additional studies are needed so that the reasons for diagnostic delay are understood and early diagnosis and management of axSpA are enabled.

Characteristics of patients with axial spondyloarthritis by geographic regions: PROOF multicountry observational study baseline results.

ObjectivesTo compare demographic and clinical characteristics of patients with axial SpA (axSpA) across geographic regions.MethodsPatients With Axial Spondyloarthritis: Multicountry Registry of Clinical Characteristics (PROOF) is an observational study that enrolled recently diagnosed (≤1 year) axSpA patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria from rheumatology clinical practices in 29 countries across six geographic regions. Demographics and disease-related parameters were collected. Here we present baseline data for patients who were classified as radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA) confirmed by central reading.ResultsOf the 2170 patients enrolled, 1553 were classified based on central evaluation of sacroiliac radiographs [r-axSpA: 1023 (66%); nr-axSpA: 530 (34%)]. Patients with nr-axSpA had a significantly higher occurrence of enthesitis (40% vs 33%), psoriasis (10% vs 5%) and IBD (4% vs 2%) vs r-axSpA patients. Significant differences in axSpA characteristics were observed between geographic regions. The highest occurrence of peripheral arthritis (60%), enthesitis (52%) and dactylitis (12%) was in Latin America, and the lowest was in Canada (9%, 9% and 2%, respectively). The occurrence of uveitis and psoriasis was highest in Canada (18% and 14%, respectively) and lowest in China (6% and <1%, respectively). IBD was highest in Arabia (21%), and no cases were observed in China. In multivariable analysis adjusted for factors potentially affecting peripheral and extramusculoskeletal manifestations, geographic regions still exhibited significant differences in frequencies of uveitis (P < 0.01), psoriasis (P < 0.0001) and peripheral arthritis (P < 0.0001).ConclusionThe multinational PROOF study of axSpA patients showed significant regional differences in peripheral and extramusculoskeletal manifestations of SpA, which could be considered in management guidelines and clinical trials.

Whole-body magnetic resonance imaging vs. clinical evaluation of enthesitis in patients with spondyloarthritis

Whole-body magnetic resonance imaging vs. clinical evaluation of enthesitis in patients with spondyloarthritis

Adult-onset Still's disease or systemic-onset juvenile idiopathic arthritis and spondyloarthritis: overlapping syndrome or phenotype shift?

Systemic-onset JIA (SJIA) and adult-onset Still's disease (AOSD) are the same sporadic systemic auto-inflammatory disease. SpA is a group of inflammatory non-autoimmune disorders. We report the observations of eight patients with SJIA/AOSD who also presented features of SpA during their disease evolution and estimate the prevalence of SpA in SJIA/AOSD. This was a retrospective national survey of departments of paediatric and adult rheumatology and internal medicine. To be included, SJIA patients had to fulfil the ILAR criteria, AOSD patients the Yamaguchi or Fautrel criteria, and all patients the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial or peripheral SpA, ESSG criteria for SpA or Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA. The data were collected with a standardized form. Eight patients (five adults) were identified in one paediatric and two adult departments. In all but one patient, SpA manifestations occurred several years after SJIA/AOSD onset [mean (s.d.) delay 6.2 (3.8) years]. Two patients had peripheral and three axial SpA, and four later exhibited PsA and one SAPHO syndrome. The prevalence of SpA in an adult cohort of 76 patients with AOSD was 6.58% (95% CI 2.17, 14.69), greater than the prevalence of SpA in the French general population (0.3%; 95% CI 0.17, 0.46). The prevalence of SpA in an SJIA cohort of 30 patients was 10% (95% CI 2.11, 26.53), more than that reported in the general population of industrialized countries, estimated at 0.016-0.15%. While the temporal disassociation between SpA and AOSD in most cases might suggest a coincidental finding, our work raises the possibility of an SpA/AOSD spectrum overlap that needs further study.

Quantification of Bone Marrow Edema by MRI of the Sacroiliac Joints in Patients Diagnosed with Axial Spondyloarthritis: Results from the ESPeranza Cohort

Objective: To evaluate whether the quantification of bone marrow edema (BMO) of the sacroiliac (SI) joints by magnetic resonance imaging (MRI) improves capacity for axial spondyloarthritis (axSpA) classification in comparison with the assessment of sacroiliitis by Assessment of SpondyloArthritis international Society (ASAS) classification criteria. Method: This prospective study from the ESPeranza cohort involved 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 other diagnoses that were not spondyloarthritis (n = 28). Measures of diagnostic usefulness [area under the curve (AUC), sensitivity, specificity, Youden’s J statistic, positive and negative likelihood ratios (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 human leucocyte antigen (HLA)-B27 positive and negative. Results: The AUC value with BMO quantification was 0.919 [95% confidence interval (CI) 0.799–1] for HLA-B27-positive patients and 0.884 (95% CI 0.764–1) for HLA-B27-negative patients. A SCAISS cut-off 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 BMO improves the predictive capacity of MRI of the SI joints, for both HLA-B27-positive and HLA-B27-negative patients.Axial spondyloarthritis (axSpA) has a dramatic impact on physical function and quality of life (1). Despite its significant impact, patients with axSpA are normally diagnosed several years after presenting symptoms (2). In this respect, magnetic resonance imaging (MRI) of the sacroiliac (SI) joints has gained significance over the past decade, particularly in the early stages of the disease. Nowadays, imaging tests and human leucocyte antigen (HLA)-B27 testing are among the most important diagnostic procedures for patients with suspected axSpA.

Aksiyal Spondiloartritte Fibromiyaljinin Hastalık Aktivitesi Değerlendirilmesine ve Tedavi Yanıtına Etkisi

Aim: Spondyloarthritis represents a group of diseases with common clinical features. When axial symptoms are predominant, the disease is called axial SpA (axSpA). Fibromyalgia frequently accompanies rheumatological diseases and affects the evaluation of disease activity measurements and treatment responses. In this study, we aimed to compare axSpA patients with and without accompanying fibromyalgia syndrome (FS). &#x0D; Material and Method: The patients with axSpA were retrospectively reviewed according to the Assessment of Spondyloarthritis international Society classification criteria. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate, and C-reactive protein data were used to evaluate disease activity. The Bath Ankylosing Spondylitis Functional Index (BASFI) was used to evaluate the functional status of the patients.&#x0D; Results: The study included a total of 300 patients, including 162 (54%) males and 138 (46%) females. The median age of the patients (25%-75% IQR) was 35 (30-46) years. In the comparison of the two axSpA groups with and without FS, age, BASFI, ESR and CRP levels, and the rate of receiving biological therapy were similar. In the FS group, female gender was dominant (n = 46, 92%; p = 0.000) and the rates of peripheral arthritis and BASDAI were significantly higher (p = 0.024 and p = 0.004, respectively).&#x0D; Conclusion: AxSpA is frequently accompanied by FS, especially in women. The symptoms of FS cause an increase in disease activity scores. Therefore, it is evaluated as low treatment response. The disease activity of FS and axSpA should be carefully evaluated to lower treatment costs and apply more accurate treatment.

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

BackgroundAxial 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.MethodsSeventy-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.ResultsHigher 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).ConclusionsOur study suggested that LMR might be an important inflammatory marker to identify axial SpA and assess disease activity and X-ray stage of sacroiliitis.

Secukinumab in axial spondyloarthritis: a narrative review of clinical evidence.

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease characterized by inflammation and new bone formation in the axial skeleton. AxSpA is considered a spectrum of disease that includes two subtypes identified by the Assessment in SpondyloArthritis International Society classification criteria, namely, radiographic (r-axSpA usually referred to as ankylosing spondylitis) and non-radiographic axSpA (nr-axSpA). Although the burden of disease appears similar between the two classified subtypes, the degree of inflammation, as assessed by magnetic resonance imaging and C-reactive protein, and the degree of new bone formation are significantly higher in r-axSpA than in nr-axSpA. Nevertheless, axSpA is considered one disease with different courses. International guidelines for the management of axSpA have outlined treatment goals focused on control of signs and symptoms, inflammation, prevention of progressive structural damage, preservation of physical function, normalization of social participation and improvement of quality of life. The pathogenesis of axSpA has not been completely elucidated to date. A strong link between human leukocyte antigen B27 and axSpA, however, has been identified, and the success of anti-tumour necrosis factor and anti-interleukin (IL)-17A therapy has highlighted some of the key pro-inflammatory cytokines involved. The anti-IL-17A monoclonal antibody secukinumab is approved for the treatment of ankylosing spondylitis and nr-axSpA in the European Union and United States. In this narrative review, we discuss data for secukinumab in axSpA from randomized controlled trials, including MEASURE trials in AS and PREVENT in nr-axSpA, and real-world evidence.

Assessment of plasma microRNA potentials as a non-invasive biomarker in patients with axial spondyloarthropathy.

It is assumed that abnormally expressed MicroRNAs (miRNAs) may be present in the plasma of patients with radiographic axial spondyloarthropathy (rad-AxSpA). Thus, the present study was conducted with the aim of investigating the expression profile of miRNAs in patients with rad-AxSpA. A total of 15 patients diagnosed with rad-AxSpA according to the Assessment of the SpondyloArthritis International Society (ASAS) classification criteria and nine healthy controls matched for age and gender were included in the study. Demographic data were collected, and disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Peripheral blood samples were collected, and miRNAs were extracted. The expression of microRNAs was analyzed using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) by the miScript miRNA PCR Array Human Inflammatory Response and Autoimmunity. A total of 84 miRNA profiles were evaluated, and expressions in the study and control groups were compared. When compared to the control group, 6 miRNAs (miR-125b-5p, miR-144-3p, miR-19a-3p, miR-20a-5p, miR-29c-3p, miR-30b-5p) were detected to be upregulated, and 42 miRNAs were detected to be downregulated in the rad-AxSpA group. A p-value < 0.05 was accepted as statistically significant. A significant association was found between miR-145-5p and BASDAI (p = 0.04941). MiR-144-3p, miR-302b-3p, miR-381-3p, miR-497-5p, miR-511-5p, and miR-9-5p were found to be significantly upregulated in the HLA-B27+ patients (p = 0.03063). Abnormal miRNA expressions were detected in the plasma of the patients with rad-AxSpA. It was concluded that comprehensive studies should be continued to define these miRNAs as diagnostic biomarkers for rad-AxSpA in order to detect its association with Ankylosing Spondylitis disease activity.

Diagnostic performance of sacroiliac joint MRI and added value of spine MRI to detect active spondyloarthritis

PurposeTo investigate the diagnostic performance of sacroiliac joint (SIJ) magnetic resonance imaging (MRI) and the incremental value of spine MRI to “predict” clinical disease activity in patients with axial spondyloarthritis (axSpA). Materials and methodsThis cross-sectional study included adult patients with known axSpA according to the SpondyloArthritis International Society (ASAS) classification criteria, radiological arm. MRI disease activity was scored semi-quantitatively for SIJ and total spine MRI in each patient. Two cut-off levels (≥ 1.3 and ≥ 2.1) for ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP) were considered for clinical disease activity categorization. MRI scores were first evaluated individually. Then, SIJ score was combined with the score from a spine segment (lumbar, cervical, thoracic or total spine) to build a bi-parametric model using a classification tree. Receiver operating characteristic (ROC) curves were constructed to evaluate the classification performance according to disease activity category of these models. ResultsForty-four patients (30 men, 14 women; mean age, 37 years±10 [SD] [range: 17–64 years]) with a mean disease duration of 5 years±8 (SD) (range: 0–35 years) were included. Thirty-six patients (36/44; 82%) had ASDAS-CRP≥1.3 and 27 patients (27/44; 61%) had ASDAS-CRP≥2.1. The most frequently involved spinal segment was mid-thoracic (T7-T8). The SIJ MRI score was an informative model to identify active axSpA (AUC≥0.7, regardless of the cut-off level on ASDAS-CRP). Performance of bi-parametric models based on “SIJ+thoracic spine” (for detecting patients with ASDAS-CRP≥1.3) or “SIJ+total spine” (for detecting patients with ASDAS-CRP≥2.1) outperformed that of the individual SIJ score (P<0.05). ConclusionThe combination of MRI of the SIJ and spine allows to accurately discriminate between active and inactive axSpA, outperforming SIJ MRI alone.

Elevated Tenascin-C Serum Levels in Patients With Axial Spondyloarthritis.

This study aimed to examine serum tenascin C (TNC) in different subsets of axial spondyloarthritis (axSpA) patients. Sixty-one patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA and 20 healthy subjects (HS) were included in study. Based on imaging, patients were classified as non-radiographic (n=16) and radiographic (n=45) axSpA. TNC serum levels were determined by ELISA. Disease-related factors including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP) levels, were determined. TNC levels were elevated in axSpA patients [535.3 (457.7-677.2) ng/ml] compared to HS [432.1 (329.1-565.9) ng/ml, p=0.007]. Dividing axSpA into radiographic and non-radiographic subsets, the difference in TNC was observed between the radiographic subset and HS [535.3 (434.5-677.2) vs. 432.1 (329.1-565.9) ng/ml, p=0.022]. TNC levels did not correlate with disease activity measures (serum CRP or BASDAI). Nevertheless, the weak correlation of TNC levels with different disease stages (r=0.25, p=0.025) was found, with the highest levels in patients with syndesmophytes. TNC levels are elevated across various subsets of axSpA, and although not related to systemic disease activity, TNC levels might reflect chronic structural spinal changes in axSpA patients. However, its specific role in bone metabolism should be elucidated in further studies.

Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE.

IntroductionAchievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP.MethodsC-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years’ symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48).ResultsIn total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious.ConclusionsOver 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified.Trial RegistrationNCT02505542.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00214-7) contains supplementary material, which is available to authorized users.

Prevalence of Spondyloarthritis Among Patients Who Underwent Lumbar Disc Herniation Surgery.

This study aims to estimate the prevalence of spondyloarthritis (SpA) among patients who had been surgically treated for lumbar disc herniation (LDH), according to the modified New York (mNY) criteria for the diagnosis of ankylosing spondylitis and Amor, the European Spondyloarthropathy Study Group (ESSG), the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for SpA. The study included 321 patients (142 males, 179 females; mean age 49±10.8 years; range, 18 to 79 years) who underwent LDH surgery between April 2008 and May 2012 in the neurosurgery clinic of our hospital. Patients were contacted by phone on at least two attempts. Totally, 123 patients accepted to come to the outpatient clinic, while the remaining 198 agreed to be interviewed on the phone. Patients who agreed to come to the outpatient rheumatology clinic underwent clinical examination, and pelvic X-ray and magnetic resonance imaging (MRI) scan of the sacroiliac joints when indicated. Inflammatory back pain was diagnosed in 108 patients (34%) and 40 patients (13%) according to Calin criteria and the ASAS criteria, respectively. Prevalence of SpA among all patients was estimated as 17.7% according to the ESSG criteria, and 8.7% according to Amor criteria. Five of the 308 pelvic radiographs had definite radiographic sacroiliitis as required by the mNY criteria. Four patients had a characteristic pattern of bone marrow edema on MRI examination in accordance with the ASAS definitions. The overall prevalence of sacroiliitis (MRI sacroiliitis+X-ray sacroiliitis) among the patients who came to the clinic was 7.3% ([4+5]/123). The relatively increased prevalence of SpA among patients who underwent LDH surgery indicates the necessity of increasing awareness on the new concept of axial SpA for specialists treating patients with low back pain.

The Association Between Age and Clinical and Radiological Activity in Axial Spondyloarthritis

Objective: To investigate the associations between age and clinical and radiological disease activities in axial SpA. Methods: One hundred and twenty-one patients fulfilling the Assessment of SpondyloArthritis International Society Classification Criteria for axial SpA were included in analyses. Patient demographics, disease activity and radiographic scores, as well as magnetic resonance imaging (MRI) with diffusion weighted imaging derived apparent diffusion coefficient values (DWI(ADC)), were compared between patients aged &gt; 40 and [Formula: see text] 40 years at a cross-sectional level. Variables with significant differences in univariate analyses were used as dependent variables in multivariate linear regression models adjusted for potential confounding/contributing factors. Results: Multivariate analysis showed that increasing age was significantly associated with higher Bath Ankylosing Spondylitis Functional Index (B = 0.04, p &lt; 0.01) and Bath Ankylosing Spondylitis Metrology Index scores (B = 0.04, p &lt; 0.01); as well as higher modified Stoke Ankylosing Spondylitis Spine Score (B = 0.41, p &lt; 0.01). On MRI, increasing age was associated with a lower DWI(ADC) (B = (-0.01), p &lt; 0.01) of the SI joints, but higher DWI(ADC) values of the axial spine (B = 0.01, p = 0.01). Conclusion: Increasing age in SpA was associated with greater functional impairment and structural damage, more inflammation of the axial spine, but less inflammation of the SI joints. Our findings are consistent with the traditional belief that SpA is an “ascending disease” and highlights the importance of different modalities of MRI in the diagnosis and disease monitoring of SpA.