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Background: In axial spondyloarthritis (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), enthesitis is a hallmark clinical feature that can be assessed by the SPARCC index, LEI, MASES and MEI. These indices evaluate different locations, which may identify different numbers of patients with enthesitis among SpA subtypes. Thus, the aim of this study was to evaluate whether the proportion of patients with at least one enthesitis across these three most prevalent SpA subtypes differs according to the index used and to evaluate the level of agreement among indices in detecting patients with enthesitis., Methods: A total of 4185 patients (2719 axSpA, 433 pSpA and 1033 PsA) from the international and cross-sectional ASAS-PerSpA study were included. The proportion of patients with enthesitis identified by the indices was evaluated across the three diseases. Pairwise agreement between indices was computed using Cohen's kappa., Results: The prevalence rates of patients with at least one enthesitis according to the MEI, MASES, SPARCC index and LEI were 17.2%, 13.5%, 10.7%, and 8.3%, respectively. In axSpA, the indices that identified the most patients with enthesitis were the MEI and MASES (98.7% and 82.4%, respectively); in pSpA and PsA, the indices that identified the most patients with enthesitis were the MEI and SPARCC index (MEI: 100% and SPARCC: 84.6%; MEI: 97.3% and SPARCC: 77%, respectively). In the total population, the MASES vs. MEI showed the strongest agreement (absolute agreement 96.3%; kappa: 0.86); similar results were obtained in axSpA patients (97.3%; 0.90). In pSpA and PsA patients, the SPARCC vs. MEI (97.2%; 0.90 and 95.4%; 0.83, respectively) showed the strongest agreement., Conclusions: These results suggest that the prevalence of patients with enthesitis across SpA subtypes differs depending on the disease and the index used. The MEI and MASES appeared best for assessing enthesis in SpA and axSpA, while the MEI and SPARCC index appeared best for assessing enthesitis in pSpA and PsA., (© 2023. The Author(s).)

Background: An inverse association between alcohol consumption and disease activity and functional impairment has been observed in patients with spondyloarthritis (SpA). However, neither this association nor the influence of smoking has been investigated in peripheral manifestations of SpA., Objectives: The objective of this study was to analyze the association between smoking and alcohol consumption and the presence of peripheral musculoskeletal manifestations (arthritis, enthesitis or dactylitis) and to determine the specific location of these manifestations., Methods: Patients from the worldwide cross-sectional ASAS-PerSpA study with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or psoriatic arthritis (PsA) according to their rheumatologist were included. Generalised linear mixed models used peripheral manifestation (or location) as a dependent variable, smoking status and alcohol consumption as fixed effects and country as a random effect. The interaction between smoking and alcohol was tested. Analyses were performed for each diagnosis (axSpA, pSpA and PsA)., Results: A total of 4181 patients were included. In axSpA patients, smoking was associated with a lower prevalence of any peripheral manifestation, and current alcohol consumption was associated with a lower prevalence of both current arthritis and current enthesitis. In pSpA patients, current alcohol consumption was associated with a lower prevalence of current arthritis or enthesitis. In PsA patients, a significant association was found for arthritis with smoking and for enthesitis with alcohol consumption, and current alcohol consumption was associated with a lower prevalence of current arthritis or enthesitis., Conclusion: Taking into account the country, smoking and alcohol are associated with a lower prevalence of peripheral manifestations., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA)., Methods: This is a cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected., Results: 888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs., Conclusion: Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA)., Methods: This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection., Results: 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients., Conclusion: Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To describe the time of onset of acute anterior uveitis (AAU) relative to the appearance of rheumatic symptoms and to determine its association with the evolution of the spondyloarthritis (SpA) in terms of activity, structural damage, functional ability and treatment., Methods: This was a cross-sectional study with data extracted from the REGISPONSER (SpA Registry of the Spanish Rheumatology Society). Thirty-one centres participated, and patients with SpA according to the ESSG criteria were included from 2004 to 2007. Patients were classified according to the time of uveitis appearance with regard to rheumatic symptom onset (before, concomitant with, or after rheumatic symptom onset). We compared the clinical characteristics, disease activity, radiographic damage and functional ability between "AAU before or concomitant with rheumatic symptoms" and "AAU after rheumatic symptoms onset". Finally, we compared whether the time of appearance of AAU had an impact on the use of conventional and biological disease-modifying antirheumatic drugs (csDMARDs and bDMARDs, respectively)., Results: A total of 2367 patients were included in REGISPONSER, with an AAU prevalence of 16.2% (379 patients). Patients with AAU before/concomitant with rheumatic symptom onset (n=59) exhibited better functional ability (BASFI, OR 0.85 [0.73-0.99]) and less structural damage (spinal BASRI, OR 0.88 [0.79-0.99]). Additionally, this group of patients was older at SpA symptom onset (OR 1.05 [1.02-1.09]) and had a shorter diagnosis delay (OR 0.90 [0.84-0.96]) compared patients with AAU after rheumatic symptom onset (n=229). No statistically significant differences in the use of DMARDs were noted (27.9% vs 23.2% for csDMARD use and 15.3% vs 20.3% for bDMARD use in patients with AAU before or concomitant with rheumatic symptom onset vs after rheumatic symptom onset, respectively)., Conclusion: Patients presenting with a first episode of AAU before/concomitant with the onset of rheumatic symptoms had less severe disease (better functional ability and less structural damage) and a shorter diagnosis delay; however, the time of AAU onset did not impact the treatments received., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objectives: To compare the atherosclerosis disease burden between ankylosing spondylitis (AS) and non-radiographic (nr) axial spondyloarthritis (axSpA) and establish a model that allows to identify high-cardiovascular (CV) risk in axial spondyloarthritis patients., Methods: Cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort aimed to study atherosclerosis in axSpA. Carotid ultrasound (US) was performed to determine the carotid intima-media wall thickness (cIMT) and detect the presence of carotid plaques. The European cardiovascular disease risk assessment model, the Systematic COronary Risk Evaluation (SCORE), was also applied., Results: A set of 639 patients with AS and 167 patients with nr-axSpA without history of CV events were recruited. AS patients were older showing more CV risk factors and higher values of C reactive protein and erythrocyte sedimentation rate (ESR) than those with nr-axSpA. However, no difference in the prevalence of carotid plaques or in the cIMT was found between both groups in the adjusted analysis. The percentage of patients reclassified from the low and moderate CV risk categories to the very high-risk category due to the presence of carotid plaques was comparable in AS and nr-axSpA (10.7% versus 10.1% and 40.5% versus 45.5%, respectively). A model containing age, BASFI and ESR applied to moderate risk axSpA patients identified 41% of these patients as having very high-risk patients with high specificity (88%)., Conclusion: The atherosclerosis burden is similar in nr-axSpA and AS. As occurred for AS, more than 40% of axSpA patients included in the category of moderate CV risk according to the SCORE are reclassified into very high risk after carotid US, and a clinically relevant proportion of them can be detected by applying a model containing age, BASFI and ESR., Competing Interests: Declaration of Competing Interest I am pleased to inform that the authors of this manuscript have no competing interests to declare, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory form of arthritis in which tumor necrosis factor (TNF)-α, a potent inducer of inflammatory response and a key regulator of innate immunity and of Th1 immune responses, plays a central role. NETosis is a mechanism of innate immune defense that is involved in diverse rheumatology diseases. Nevertheless, spontaneous NETosis generation in r-axSpA, its association to disease pathogenesis, and the NETosis involvement on anti-TNF-α therapy's effects has never been explored., Methods: Thirty r-axSpA patients and 32 healthy donors (HDs) were evaluated. Neutrophil extracellular trap (NET) formation, mediators of signal-transduction cascade required for NETosis induction and cell-free NETosis-derived products were quantified. An additional cohort of 15 r-axSpA patients treated with infliximab (IFX) for six months were further analyzed. In vitro studies were designed to assess the effects of IFX in NETosis generation and the inflammatory profile triggered., Results: Compared to HDs, neutrophils from r-axSpA patients displayed augmented spontaneous NET formation, elevated expression of NET-associated signaling components, nuclear peptidylarginine deiminase 4 translocation and increased citrullinated histone H3. Furthermore, patients exhibited altered circulating levels of cell-free NETosis-derived products (DNA, nucleosomes and elastase). Additional studies revealed that cell-free NETosis-derived products could be suitable biomarkers for distinguish r-axSpA patients from HDs. Correlation studies showed association between cell-free NETosis-derived products and clinical inflammatory parameters. Besides, nucleosomes displayed potential as a biomarker for discriminate patients according to disease activity. IFX therapy promoted a reduction in both NETosis generation and disease activity in r-axSpA patients. Mechanistic in vitro studies further unveiled the relevance of IFX in reducing NET release and normalizing the augmented inflammatory activities promoted by NETs in mononuclear cells., Conclusions: This study reveals that NETosis is enhanced in r-axSpA patients and identifies the NETosis-derived products as potential disease activity biomarkers. In addition, the data suggests the potential role of NET generation analysis for assessment of therapeutic effectiveness in r-axSpA.