Background: Cartilage degradation is a hallmark in both osteoarthritis (OA) and rheumatoid arthritis (RA). Ex vivo cartilage models offer the potential to study disease processes butare surprisingly rarely used. Objectives: Here we investigate the effect of synovial tissue and stimulation with TNF-α on cartilage degradation in a physiologically relevant coculture-model of synovial membrane andcartilage. Methods: Cartilage andsynovial membranewere collected frompatientswith RA and OA who underwent joint replacement. Cartilage was cultivated either alone or with synovial membrane in medium with or without TNF α as a stimulant for up to 28 days. The
Background Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. An inception cohort prospectively followed for 6 and 14 months was studied to validate the results in early cases and analyze if cluster assignment was modified with time. Results Four clusters were identified Three aberrant clusters were ‘acute phase inflammatory’, ‘T cell immunity’, and ‘interferon’, each including all diagnoses, were defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern, to which 74% of healthy controls clustered with patients. The inception cohort showed that most patients were either assigned always to the same cluster or moved from the healthy-like cluster to a single aberrant cluster resembling the relapsing-remitting dynamic of these diseases, showing that single aberrant molecular signatures characterize each individual patient. Conclusions Patients with SADs share molecular signatures and can be therefore stratified into three disease clusters differentiating each patient into a specific molecular disease pathway. Such assignment is stable with time. These results have important implications for understanding disease progression and therapy design marking a paradigm shift in our view of SADs. Acknowledgment This work has been supported through a grant from the Innovative Medicines Initiative Joint Undertaking No. 115565 and in-kind and in-cash contributions from the EFPIA partners. G.B. is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry), through the Sara Borrell subprogram (CD18/00153). The authors would like to particularly express their gratitude to the patients, nurses and many others who helped directly or indirectly in the consecution of this study.
Objective. To develop an alternative Ankylosing Spondylitis Disease Activity Score (ASDAS) to be used in research settings in axial SpA (axSpA) when Patient Global Assessment (PGA) is unavailable in databases.Methods. Longitudinal data from four axSpA cohorts and two randomized controlled trials were combined. Observations were randomly split in a development (N = 1026) and a validation cohort (N = 1059) . Substitutes of PGA by BASDAI total score, single or combined individual BASDAI questions, and a constant value, were established in the development cohort. Conversion factors for each substitute were defined by Generalized Estimating Equations, obtaining seven 'alternative' formulae. Validation was performed in the validation cohort according to the OMERACT filter, taking into consideration: (i) truth (agreement with original-ASDAS in the continuous score, by intraclass correlation coefficient and in disease activity states, by weighted kappa); (ii) discrimination [standardized mean difference of ASDAS scores between high/low disease activity states defined by external anchors, e.g. Patient Acceptable Symptom State; agreement (kappa) in the percentage of patients reaching ASDAS improvement criteria according to alternative vs original formulae]; and (iii) feasibility.Results. Comparing various options, alternative-ASDAS using BASDAI total as PGA replacement proved to be: truthful (intraclass correlation coefficient =0.98, kappa =0.90), discriminative [ASDAS scores between Patient Acceptable Symptom State no/yes: standardized mean difference =1.37 (original-ASDAS standardized mean difference =1.43); agreement with original-ASDAS in major improvement/clinically important improvement criteria: kappa =0.93/0.88] and feasible (BASDAI total often available, as questions required for the ASDAS; conversion coefficient approximate to 1).Conclusion. Alternative-ASDAS using BASDAI total score as PGA replacement is the most truthful, discriminative and feasible instrument.
An amendment to this paper has been published and can be accessed via the original article.
Aims: To evaluate the association of estimated cardiovascular (CV) risk and subclinical atherosclerosis with radiographic structural damage in patients with axial spondyloarthritis (axSpA). Methods: Cross-sectional study including 114 patients axSpA from the SpA registry of Córdoba (CASTRO) and 132 age- and sex-matched healthy controls (HCs). Disease activity and the presence of traditional CV risk factors were recorded. The presence of atherosclerotic plaques and carotid intima media thickness (cIMT) were evaluated through carotid ultrasound and the SCORE index was calculated. Radiographic damage was measured though modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The association between mSASSS and SCORE was tested using generalized linear models (GLM), and an age-adjusted cluster analysis was performed to identify different phenotypes dependent on the subclinical CV risk. Results: Increased traditional CV risk factors, SCORE, and the presence of carotid plaques were found in axSpA patients compared with HCs. The presence of atherosclerotic plaques and SCORE were associated with radiographic structural damage. The GLM showed that the total mSASSS was associated independently with the SCORE [β coefficient 0.24; 95% confidence interval (CI) 0.10–0.38] adjusted for disease duration, age, tobacco, C-reactive protein, and non-steroidal anti-inflammatory drugs (NSAID) intake. Hard cluster analysis identified two phenotypes of patients. Patients from cluster 1, characterized by the presence of plaques and increased cIMT, had a higher prevalence of CV risk factors and SCORE, and more structural damage than cluster two patients. Conclusion: Radiographic structural damage is associated closely with increased estimated CV risk: higher SCORE levels in axSpA patients were found to be associated independently with mSASSS after adjusting for age, disease duration, CRP, tobacco and NSAID intake.
Objectives: To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). Methods: All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Results: 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]. Conclusion: Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.
Objective. To evaluate whether the presence of psoriasis influences the clinical expression, disease activity and disease burden in both axial and peripheral phenotypes of spondyloarthritis (SpA). Methods. Patients from the Spanish REGISPONSER registry classified as having SpA according to the ESSG criteria were included. Patients were classified as psoriatic or non-psoriatic depending on the presence of cutaneous or nail psoriasis; thereafter, they were classified as having either axial [presence of radiographic sacroiliitis OR inflammatory back pain (IBP)] or peripheral phenotype (absence of radiographic sacroiliitis AND absence of IBP AND presence of peripheral involvement). Pair-wise univariate and multivariate analyses among the four groups (psoriatic/non-psoriatic axial phenotypes and psoriatic/non-psoriatic peripheral phenotypes) were performed with adjustment for treatment intake. Results. A total of 2296 patients were included in the analysis. Among patients with axial phenotype, psoriasis was independently associated (P < 0.05) with HLA-B27(+) [odds ratio (OR) 0.27], uveitis (OR 0.46), synovitis (ever) (OR 2.59), dactylitis (OR 2.78) and the use of conventional synthetic DMARDs (csDMARDs) (OR 1.47) in comparison with non-psoriatic patients. Among patients with peripheral phenotype and adjusting for csDMARD intake, psoriasis was independently associated with higher age at disease onset (OR 1.05), HLA-B27(+) (OR 0.14) and heel enthesitis (OR 0.22). Higher scores for patient-reported outcomes and greater use of treatment at the time of the study visit were observed in psoriatic patients with either axial or peripheral phenotype. Conclusion. These findings suggest that, among all patients with SpA, psoriasis is associated with differences in clinical expression of SpA, a greater disease burden and increased use of drugs.
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. 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. 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. 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.
ObjectiveTo estimate the 6-year radiographic progression of sacroiliitis in patients with early spondyloarthritis (SpA).Patients and methodsSacroiliac joint (SIJ) radiographs (baseline and 6 years) of 94 patients with recent-onset SpA from the Esperanza cohort were scored, blindly and in a random order, by nine readers. The modified New York criteria were used to define the presence of sacroiliitis. As the gold standard for radiographic (r) sacroiliitis, the categorical opinion of at least five readers was used. Progression was defined as the shift from non-radiographic (nr) to r-sacroiliitis.ResultsIn the 94 SIJ radiographs (baseline and 6 years), 78/94 (83%) pairs of radiographs had not changed from baseline to 6 years. Sacroiliitis was present in 20 patients at baseline (21.3%) and in 18 (19.2%) patients at 6 years; 11 patients had sacroiliitis at both the baseline and final visits; 9 patients changed from baseline r-sacroiliitis to nr-sacroiliitis at 6 years, and 7 changed from baseline nr-sacroiliitis to r-sacroiliitis at 6 years. The mean continuous change score (range: −8 to +8) was 2.80 at baseline and 2.55 at 6 years (mean net progression of −0.25). The reliability of the readers was fair (mean inter-reader kappa of 0.375 (0.146–0.652) and mean agreement of 73.7% (58.7–90%)).ConclusionIn the early SpA Esperanza cohort, progression from nr-axSpA to r-axSpA over 6 years was not observed, although the SIJ radiographs scoring has limitations to detect low levels of radiographic progression.
Objective: To analyze the relationship between complement component 3 (C3) and the prevalence of cardiometabolic risk factors and disease activity in the rheumatic diseases having the highest rates of cardiovascular morbidity and mortality: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Methods: This is a cross-sectional study including 200 RA, 80 PsA, 150 axSpA patients and 100 healthy donors. The prevalence of cardiometabolic risk factors [obesity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, apolipoprotein B/apolipoprotein A (apoB/apoA) and atherogenic risks and hypertension] was analyzed. Serum complement C3 levels, inflammatory markers and disease activity were evaluated. Cluster analysis was performed to identify different phenotypes. Receiver operating characteristic (ROC) curve analysis to assess the accuracy of complement C3 as biomarker of insulin resistance and disease activity was carried out. Results: Levels of complement C3, significantly elevated in RA, axSpA and PsA patients, were associated with the prevalence of cardiometabolic risk factors. Hard clustering analysis identified two distinctive phenotypes of patients depending on the complement C3 levels and insulin sensitivity state. Patients from cluster 1, characterized by high levels of complement C3 displayed increased prevalence of cardiometabolic risk factors and high disease activity. ROC curve analysis showed that non-obesity related complement C3 levels allowed to identify insulin resistant patients. Conclusions: Complement C3 is associated with the concomitant increased prevalence of cardiometabolic risk factors in rheumatoid arthritis and spondyloarthritis. Thus, complement C3 should be considered a useful marker of insulin resistance and disease activity in these rheumatic disorders.
Objectives: To evaluate the association between low disease activity according to the new ASDAS nomenclature and the physician therapeutic decisions in patients with axial spondyloarthritis (axSpA). Material and Methods: Longitudinal retrospective study including patients diagnosed with axSpA receiving a tumor necrosis factor-inhibitor between January 2014 and June 2019 as a first treatment. For each visit, disease activity was determined afterwards according to the new ASDAS nomenclature (inactive, low, high and very high activity), and the physician's therapeutic decision was recorded. The association between disease activity and the physician's decision was evaluated through descriptive statistics. Results: A total of 304 visits of 104 patients with axSpA were analyzed. For those visits where a low activity ASDAS score was obtained, the physician's therapeutic decision was no escalation of treatment in 98.2% of cases. However, for those visits with a high or very high disease activity ASDAS score, the physician's therapeutic decision was to escalate treatment in 33.7% and 82.8% of cases respectively. Conclusions: The state measured by the ASDAS index formerly defined as 'moderated disease activity' is considered in clinical practice as low disease activity' because of the physician's choice in these situations to not-escalate the treatment. Our data substantiate the recent updating in ASDAS nomenclature. (C) 2020 Elsevier Inc. All rights reserved.
Background JAK inhibitors (JAKi) have been recently authorized in the European Union. JAKi long-term performance in the clinical practice setting still needs to be assessed. Drug survival reflects a drug’s effectiveness, safety, and tolerability; thus, it is an important measurement for real-world studies. Objectives To describe the pattern of use of JAKi in real-world dataset, and to analyze the drug survival as a group (tofacitinib+baricitinib). Methods Information was obtained from BIOBADASER III, an ongoing observational longitudinal multicenter cohort of patients with rheumatic diseases treated with biologic or targeted synthetic (b/ts) DMARDs in Spain. All subjects with current or previous JAKi use were included and followed until September 2018. Clinical characteristics of the patients were analyzed. Drug survival (overall, and for biologic-naive and biologic-experienced patients) was determined using Kaplan-Meier analysis. Results 149 patients, 75.2% women, were treated with JAKi, receiving a total of 152 cycles of treatment (50.7% tofacitinib, 49.3% baricitinib; 3 patients had both). The most frequent diagnosis was rheumatoid arthritis (RA, 92.6%), and there is a small number of off-label uses (6%), depicted at Table 1. Use on psoriatic arthritis is scarce (1.3%). Concomitant use of methotrexate (MTX) was registered in 68 patients (45.6%). Previous use of bDMARDs was high (n=124, 81.6%); drug survival rate for biologic-experienced patients was 81.7% and 78.7% at 6 and 12 months. None of the JAKi treatments in biologic-naive patients (n=18, 18.4%) were discontinued during follow-up. Pooled survival rate of JAKi was 85.0% and 82.5% at 6 and 12 months (Figure 1). Discontinuation was seen in 19 treatments (12.5%); the reasons were inefficacy (n=15, 9.9%) or adverse events (n=4, 2.6%). Conclusion The current use of JAKi in Spain is mainly in RA and as 2nd line after bDMARDs. The use of JAKi in psoriatic arthritis is still scarce and a small group of patients are treated off-label. Less than half use combination therapy with MTX. Overall survival of JAKi is superior to 80% at 12 months. A longer follow-up is needed to continue analyzing the survival of JAKi in a real-world context. Acknowledgement We thank all researchers from the BIOBADASER III group. Disclosure of Interests Valentina Emperiale: None declared, Carlos Sánchez-Piedra: None declared, Eduardo Cuende: None declared, Paloma Vela-Casasempere Grant/research support from: UCB, Abbvie, Pfizer, Roche, Bristol-Myer-Squibb (another research, not BIOBADASER related), Consultant for: UCB, Lilly, Pfizer, Roche, Bristol-Myer-Squibb, Speakers bureau: Roche, UCB, MSD, Pfizer, GSK, BMS, Lilly, María del Carmen Castro Villegas Paid instructor for: MSD, Abbvie, Pfizer, Janssen, Lilly, Roche, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Cristina Campos Fernández: None declared, Javier del Pino: None declared, Manuel Pombo: None declared, Fernando Sánchez-Alonso: None declared, Juan Jesus Gomez-Reino: None declared
Background X-Ray sacroiliitis is the cornerstone in the diagnosis of the ankylosing spondylitis (AS). It is clear that the presence of sacroiliitis is a specific lesion in long standing AS, but little evidence exists on the reliability of this image technique in early axial spondyloarthritis (axSpA), which associates with reduced structural damage. This is relevant because some rheumatologists and pharmacological authorities feel more confident with the diagnosis of AS rather than with non radiographic axial spondyloarthritis (nr-axSpA) forms. On the other hand, according to various research studies, clinicians are subject to potential bias when interpreting radiographs, influenced by their pretest clinical judgment. Objectives The aim of this study is to determine the value of X-Ray sacroiliitis in the early diagnosis of axSpA. Methods This study included 290 radiographs of the SI joints from patients of the Esperanza early spondyloarthritis cohort. Nine readers, blinded for the diagnosis, participated in the reliability exercise, all of them experienced rheumatologists and members of the Spanish spondiloarthritis working group (GRESSER). Patients with axSpa were classified as having AS if the radiographic criteria of the modified NY criteria (presence of radiographic changes in the SIJ of at least grade II bilaterally or at least grade III unilaterally) were fulfilled. The gold standard was the categorical opinion of at least five of the expert readers. For the statistical analysis, the Chi-square and Kappa tests were performed. Results The radiographic diagnosis, sensitivity, specificity, likelihood ratio, grade of agreement and mean K values compared to gold standard are showed in table 1. The concordance Kappa test was highly variable among the readers, ranging from fair to excellent. The agreement with the gold standard varied from 68 to 94% and the sensitivity and specifity, from 50-100% and 64-96%, respectively. Additionally, the number of AS was 61, with an inter-reader variability rate of 31 to 138. Larger discrepancies were observed when assessing sacroiliitis grade 2. Conclusion The diagnosis of AS in early axSpa is characterized by a marked variability. At least in doubtful cases, a second central evaluation performed by highly qualified experts should be advisable. Disclosure of Interests Eugenio de Miguel: None declared, Beatriz Joven-Ibáñez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen, Eva Galindez: None declared, Claudia Urrego-Laurín: None declared, Maria Luz García-Vivar: None declared, Cristina Fernández-Carballido: None declared, Jose Francisco Garcia LLorente: None declared, María del Carmen Castro Villegas Paid instructor for: MSD, Abbvie, Pfizer, Janssen, Lilly, Roche, Carolina Tornero: None declared, Xavier Juanola-Roura: None declared
OBJECTIVES:To develop a new equation to calculate the Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) using only the BASDAI total score and CRP.METHODS:Axial SpA (axSpA) patients from the Cordoba Spondyloarthritis Registry cohort were recruited as a derivation cohort, while a retrospective sample from the Spanish Rheumatology Society National Registry of Spondyloarthropathies and Ibero American Spondyloarhtritis Registry registers was used as a validation cohort. We built a new equation based only on the BASDAI and CRP, defining a new formula: the BASDAI-based ASDAS (BASDAS). Linear regression analysis was used to determine the coefficients of the equation in the derivation cohort and it was subsequently validated in the validation cohort.RESULTS:A total of 52 axSpA patients in the derivation cohort and 3359 patients in the validation cohort were included. In the derivation cohort, the mean BASDAS [2.24 (s.d. 0.90)] was very similar to the ASDAS-CRP [2.23 (s.d. 0.95)], with a very strong correlation (r = 0.96, P < 0.001). In the validation cohort, the mean BASDAS was 3.31 (s.d. 1.37) and the ASDAS-CRP was 3.19 (s.d. 1.27), which also had a very strong correlation (r = 0.95, P < 0.001). Intraclass correlation coefficients were excellent in both cohorts (0.963 and 0.947, respectively).CONCLUSION:The BASDAS performs similarly to the ASDAS-CRP and can be calculated with only the BASDAI total score and CRP, allowing evaluation of disease activity in retrospective studies where the individual items of the BASDAI are not available.
The objective of our study was to standardize magnetic resonance imaging (MRI) assessment of spine and sacroiliac joints in patients with axial spondyloarthritis (axSpA) and/or inflammatory spinal pain, by creating checklists and templates based on the opinions of rheumatologists and radiologists. A scientific committee developed a series of questionnaires with multiple items regarding MRI in patients with axial inflammatory pain and/or axSpA. Then an expert panel of rheumatologists and radiologists rated all items in a 9-point Likert scale. Finally, the scientific committee and the expert panel met to create the definitive documents. Several definitive checklists and templates were generated for rheumatologist-requested MRI and for radiologist-requested MRI reports of sacroiliac joint and spinal examinations. A technical requirement protocol was also agreed on. Our results could be useful in increasing understanding between rheumatologists and radiologists regarding MRI in axSpA diagnosis and follow-up.
Objectives To describe the clinical-demographic characteristics and behaviour over time (12, 24 and 60 months) of a cohort of Undifferentiated Arthritis (UA), as well as to analyze which factors are associated with the evolution towards Rheumatoid Arthritis (RA), use of Biological Therapy (BT) and the development of Cardiovascular Disease (CVD). Methods Ambispective cohort study of patients with UA evaluated longitudinally from January 2009 to 2019. We analyzed baseline clinical and laboratory variables and a Multivariate Logistic Regression was performed to determine the factors associated with RA development after 5 years of follow-up. To analyze what factors were associated with the use of BT and the presence of CVD chi-square or Fisher's test were used for binary variables, and U-Mann Whitney for continuous variables. Results 180 patients were included, 55% were women, with an average age of 49.3 (SD 16.1) years. The average duration of symptoms before the first visit was 6.9 (SD 9.9) months. 47.2% were FR+, 41% ACPA+, 20.6% HLA-DRB1 shared epitope. At the end of follow-up: 33.3% evolved to RA, 17.2% remained as palindromic rheumatism, 25% were diagnosed other chronic rheumatic diseases, 21.1% remitted spontaneously and 3.3% remained as UA. Of the 60 AR, 37 were diagnosed in the first year, 13 at second and 10 at 5 years of follow-up. During follow-up, 13 patients with RA started BT, and 12 patients presented CVD (7 of them died). Table 1 identifies the factors associated with the development of RA. The MLR identified ACPA +, OR (95% CI) = 10.69 (4.43 - 25.78), and the HLA-DRB1 shared epitope OR (95% CI) = 9.18 (2.96 - 28.48) p <0.001 as factors associated to the development of AR. We failed to identify factors associated with the use of BT, possibly due to the sample size. The factors associated with the development of CVD, where only the use of glucocorticoids as a factor associated with the presence of CVD shows statistical significance. Conclusion 1) Useful clinical and laboratory characteristics have been identified to predict which patients are at risk of developing persistent arthritis. 2) HLADRB1 shared Epitope and ACPA are predictive factors of evolution to RA. 3) Possibly the continued use of glucocorticoids, even at low doses, may be related to the development of long-term CVD Disclosure of Interests Jerusalem Calvo Gutierrez: None declared, Rafaela Ortega Castro: None declared, Clementina López-Medina: None declared, Ladehesa Pineda Lourdes: None declared, María del Carmen Castro Villegas Paid instructor for: MSD, Abbvie, Pfizer, Janssen, Lilly, Roche, Alejandro Escudero Contreras: None declared, Eduardo Collantes Estevez: None declared