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Purpose We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). Design Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. Subjects We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behcet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. Methods Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. Main outcome measures Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. Results The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. Conclusions Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.

Resumen Objetivos Analizar el riesgo de fractura calculado por FRAX® y la frecuencia de alto riesgo de fractura en la poblacion general en Espana. Metodos EPISER2016 es un estudio transversal multicentrico de base poblacional de la prevalencia de las enfermedades reumaticas en poblacion adulta en Espana. Un total de 3.154 sujetos de edad igual o superior a 40 anos (1.184 hombres y 1.970 mujeres) se seleccionaron mediante muestreo aleatorio estratificado. Las preguntas relacionadas con los factores de riesgo de fractura se realizaron mediante encuesta telefonica. El riesgo de fractura principal (RFP) y de cadera (RFC) se calcularon con la version espanola de la herramienta FRAX®, sin la inclusion de la densidad mineral osea. Para definir alto riesgo de fractura, se utilizaron los umbrales RFP ≥ 20%, RFP ≥ 10%, RFP ≥ 7,5% y RFC ≥ 3%. Resultados La mediana (rango intercuartilico) del RFP fue 2,61% (1,55-6,34%) en mujeres y 1,67% (1,15-2,87%) en hombres; la del RFC fue 0,39% (0,14-1,86%) y 0,18% (0,07-0,77%). El 3,83% de las mujeres y ningun hombre tenian un RFP ≥ 20%; el 15,71% y el 1,14% tenian un RFP ≥ 10%; el 20,62% y el 2,21%, un RFP ≥ 7,5%; y el 19,27% y el 8,05%, un RFC ≥ 3%. En las mujeres de 65 anos o mas, el RFC fue alto en el 58,09%. Conclusiones EPISER2016 nos ha permitido conocer el riesgo de fractura calculado por FRAX® y la prevalencia de alto riesgo de fractura en la poblacion general segun los diversos umbrales utilizados en Espana.

Background Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. & nbsp; Methods Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. & nbsp; Findings Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR < 0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4 +T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. & nbsp; Interpretation Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems.& nbsp; & nbsp; Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Superscript/Subscript Available

Objective The main study objective was to determine how giant cell arteritis (GCA) is diagnosed in our clinical practice and whether the EULAR recommendations have influenced the diagnostic procedures used. Methods ARTEritis of the Rheumatology Spanish Society -Sociedad Española de Reumatología (ARTESER) is a multicentre observational retrospective study conducted in 26 hospitals with support from the Spanish Society of Rheumatology. All patients diagnosed with GCA between 1 June 2013 and 29 March 2019 were included. The gold standard for the diagnosis of GCA was the judgement of the physician in charge, according to clinical criteria, supported by data available from laboratory tests, imaging studies (ultrasound, positron emission tomography (PET) and MRI/CT angiography) and temporal artery biopsy (TAB) when available. Results We included 1675 patients with GCA (mean age±SD (76.9±8.1) years, 1178women (70.3%)). Of these, 776 patients had a positive TAB (46.3%), 503 (30.0%) positive ultrasound, 245 positive PET (14.6%) and 64 positive MRI/CT angiography (3.8%). These percentages changed substantially over the study. From 2013 to 2019, the use of ultrasound in diagnosis grew from 25.8% to 52.9% and PET from 12.3% to 19.6%, while use of TAB decreased from 50.3% to 33.3%. Conclusions Biopsy was the most widely used diagnostic test for confirming GCA, but use of imaging as a diagnostic tool has grown in recent years. Following publication of the 2018 EULAR recommendations, ultrasound has displaced biopsy as the first-line diagnostic test; TAB was performed in a third and PET in a fifth of cases. Funding: Roche contributes to the financial support of this study. Acknowledgements: To the Spanish Society of Rheumatology that has promoted and provided coverage for this study. To Roche for its financial contribution that made this epidemiological study possible

We present the case of a 36-year-old woman with diffuse idiopathic skeletal hyperostosis especially at cervical spine since she was 29 years old. The only relevant feature was the use of isotretinoin at regular doses in the past for severe acne.

Resumen Introduccion La cumplimentacion del tratamiento modificador de la enfermedad es esencial para alcanzar los objetivos terapeuticos en la artritis reumatoide (AR). Sin embargo, y a pesar de la necesidad de una buena adherencia, existe evidencia de que muchos pacientes con AR no cumplen adecuadamente con la prescripcion del tratamiento indicado con farmacos moduladores de la enfermedad de accion lenta (FAME) sinteticos o convencionales. Conscientes de la importancia de este hecho, el estudio sobre observancia terapeutica en AR (estudio OBSERVAR) tiene como objetivo principal valorar los motivos de la falta de adherencia terapeutica a los FAME sinteticos en estos pacientes. Pacientes y metodos Mediante un proceso Delphi entre 18 reumatologos espanoles seleccionados aleatoriamente se determino el grado de acuerdo con 66 causas de incumplimiento seleccionadas de la bibliografia, en relacion con los FAME sinteticos en la AR. Resultados Los motivos de incumplimiento fueron consistentes en el 75,7%, si bien 3 razones (4,5%) destacaron como muy consistentes: 1) desconocer que hacer cuando se sufre un acontecimiento adverso con el FAME; 2) no llevar a cabo metodos de cribado de la adherencia por el personal sanitario para detectar a los «pacientes incumplidores» de forma temprana y 3) no aplicar intervenciones o estrategias que mejoren la adherencia terapeutica. Conclusion Para mejorar la adherencia al tratamiento de la AR con FAME sinteticos se debe informar al paciente de cada tratamiento nuevo introducido, incorporar el perfil de cumplimiento del paciente en la rutina clinica, y reforzar la motivacion del paciente al cumplimiento terapeutico mediante los metodos a nuestro alcance.

[Abstract] Background: Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. Patients and methods: A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. Results: The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. Conclusion: In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us. [Resumen] Introducción. La cumplimentación del tratamiento modificador de la enfermedad es esencial para alcanzar los objetivos terapéuticos en la artritis reumatoide (AR). Sin embargo, y a pesar de la necesidad de una buena adherencia, existe evidencia de que muchos pacientes con AR no cumplen adecuadamente con la prescripción del tratamiento indicado con fármacos moduladores de la enfermedad de acción lenta (FAME) sintéticos o convencionales. Conscientes de la importancia de este hecho, el estudio sobre observancia terapéutica en AR (estudio OBSERVAR) tiene como objetivo principal valorar los motivos de la falta de adherencia terapéutica a los FAME sintéticos en estos pacientes. Pacientes y métodos. Mediante un proceso Delphi entre 18 reumatólogos españoles seleccionados aleatoriamente se determinó el grado de acuerdo con 66 causas de incumplimiento seleccionadas de la bibliografía, en relación con los FAME sintéticos en la AR. Resultados. Los motivos de incumplimiento fueron consistentes en el 75,7%, si bien 3 razones (4,5%) destacaron como muy consistentes: 1) desconocer qué hacer cuando se sufre un acontecimiento adverso con el FAME; 2) no llevar a cabo métodos de cribado de la adherencia por el personal sanitario para detectar a los «pacientes incumplidores» de forma temprana y 3) no aplicar intervenciones o estrategias que mejoren la adherencia terapéutica. Conclusión. Para mejorar la adherencia al tratamiento de la AR con FAME sintéticos se debe informar al paciente de cada tratamiento nuevo introducido, incorporar el perfil de cumplimiento del paciente en la rutina clínica, y reforzar la motivación del paciente al cumplimiento terapéutico mediante los métodos a nuestro alcance.

Objective To investigate the prevalence, clinical characteristics and prognosis of pulmonary arterial hypertension (PAH) in adult onset Still's disease (AOSD). Methods We retrospectively reviewed all patients with AOSD diagnosed during a 33-year period in 2 referral tertiary care hospitals, selecting for analysis those who presented PAH confirmed as by right heart catheterization. A systematic review of the literature (PubMed 1990 to July 2018) was also performed, in order to determine the prognosis and the most appropriate treatment strategy for this complication. Results The overall prevalence of PAH in our AOSD population was 4.8% (2/41). Including our 2 cases, 20 well-documented patients have been reported. PAH may complicate AOSD at any time during its course, and usually occurs in patients who have persistent and severe disease, with a considerable frequency (35%) of previous or concomitant severe clinical complications. In all cases, the etiology of pulmonary hypertension was a group 1 PAH based on the 2015 ESC/ERS guidelines. Most patients in this series had advanced WHO functional classes III-IV at the time of PAH diagnosis, reflecting an important diagnostic delay. Thirty-three percent of patients had a poor outcome despite the therapy, with a mortality rate that reached 22%. The therapeutic strategy that achieved the best results was the use of glucocorticoids, immunosuppression and PAH-specific vasodilator therapy. Conclusion HAP is an under-recognized complication of AOSD that should be kept in mind in the differential diagnosis of those patients who experience dyspnea on exertion or a decrease in exercise tolerance

Resumen Objetivos Describir la metodologia del estudio de prevalencia de las enfermedades reumaticas en la poblacion adulta en Espana, EPISER 2016, asi como sus fortalezas y limitaciones. El objetivo del proyecto es estimar la prevalencia de artritis reumatoide (AR), artropatia psoriasica (APs), espondilitis anquilosante (EA), lupus eritematoso sistemico (LES), sindrome de Sjogren (SS), artrosis (de rodilla, cadera, manos, columna cervical y lumbar), fibromialgia, gota y fractura osteoporotica clinica. Material y metodo Estudio transversal multicentrico de base poblacional en el que participan 45 municipios de las 17 comunidades autonomas. La poblacion de referencia esta compuesta por adultos de 20 o mas anos residentes en Espana. La recogida de informacion se llevara a cabo mediante encuesta telefonica empleando el sistema Computer Assisted Telephone Interview (CATI). Las sospechas diagnosticas y los diagnosticos autorreferidos seran estudiadas por reumatologos del hospital de referencia de los municipios seleccionados. Analisis estadistico: se calcularan las prevalencias de enfermedades reumaticas mediante estimadores y sus IC del 95%. Se calcularan factores de ponderacion en funcion de la probabilidad de seleccion en cada una de las etapas del muestreo. Se tendra en cuenta la distribucion de la poblacion en Espana segun datos del Instituto Nacional de Estadistica. Conclusiones Los cambios sociodemograficos y en habitos de vida durante los ultimos 16 anos justifican la realizacion de EPISER 2016. El estudio ofrecera datos actualizados de prevalencia en AR, EA, APs, LES, SS, artrosis, fibromialgia, gota y fractura osteoporotica clinica. Los resultados permitiran comparar los datos con estudios de otros paises y con el EPISER 2000.

Background Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. Methods For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. Results The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). Conclusions The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA., This project was supported by UCB Pharma. The funders had no role in the study design, data analysis, data interpretation or writing the manuscript.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease characterized by a defective adaptive immune receptor repertoire (AIRR) that fails to distinguish self from non-self antigens. The AIRR is vast, encompassing four T cell receptor (TCR) and three B cell receptor (BCR) chains, each of which displays an extraordinary amino acid sequence variability in the antigen-binding site. How the concerted action of T and B cell clones is associated with the development and clinical evolution of immune-mediated diseases is still not known. Using a new immunosequencing technology that allows the unbiased amplification of the seven receptor chains, we conducted an in-depth quantitative analysis of the seven-receptor chain variability in RA. Compared to healthy controls, the AIRR in RA was found to be characterized by a lower BCR diversity, the depletion of highly similar BCR clones, an isotype-specific signature as well as a skewed IGL chain and gene segment usage. A predictor based on quantitative multi-chain AIRR information was able to accurately predict disease, including the elusive seronegative subset of RA patients. AIRR features of the seven immune receptor chains were also different between patients with distinct clinically relevant phenotypes. Incorporating HLA variation data, we were able to identify the TCR clones that are specifically associated with the main disease risk variants. The longitudinal analysis of the AIRR revealed that treatment with Tumor Necrosis Factor (TNF) inhibitors selectively restores the diversity of B cell clones in RA patients by reducing the frequency of clones with a similar biochemical profile. The biochemical properties of the TNFi-modulated clones were also found to differ between responders and non-responders, supporting a different antigenic reactivity in the B cell compartment of these two groups of RA patients. Our comprehensive analysis of the TCR and BCR repertoire reveals a complex T and B cell architecture in RA, and provides the basis for precision medicine strategies based on the highly informative features of the adaptive immune response.

Epidemiology of RMD Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG [Abstract] Objective. Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. Methods. EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. Results. Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82–20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. Conclusions. This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. EPISER2016 was supported by Celgene, Gebro Pharma, Merck Sharp & Dohme in Spain, Pfizer, and Sanofi-Aventis, none of whom had any role in the study design, data collection, data analysis, interpretation, or writing of this manuscript. MS was financed via the Rio Hortega Contract—Health Research Fund (CM17/00101), the Sanitary Research Fund integrated in the National Plan of Scientific Program, Technological Development and Innovation 2013–2016 and funded by the ISCIII-Subdirectorate General Evaluation and Promotion of Research-European Regional Development Fund (ERDF) "A way of making Europe"

Objective To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. Results We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25–3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6–36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P Conclusion ABA may be an effective and safe treatment for patients with RA-ILD.

[Resumen] Introducción. La Sociedad Española de Reumatología elaboró en el año 2000 el estudio EPISER2000 para conocer la prevalencia de la artrosis y otras enfermedades reumáticas en España. Los cambios sociodemográficos y en los hábitos de vida ocurridos en los últimos años en España justifican actualizar los datos de las enfermedades reumáticas (EPISER2016). Objetivo. Estimar la prevalencia de artrosis sintomática de columna cervical, columna lumbar, cadera, rodilla y mano, en población adulta en España. Material y métodos. Estudio transversal de base poblacional. Se realizó un muestreo aleatorizado polietápico estratificado y por conglomerados. Los participantes fueron contactados por teléfono para cumplimentar un cuestionario de cribado de artrosis. El reumatólogo confirmaba o descartaba el diagnóstico. Se utilizaron los criterios-clínicos-ACR para diagnosticar artrosis de manos y los criterios clínico-radiológicos-ACR para diagnosticar la artrosis de rodilla y cadera. Resultados. La prevalencia de artrosis en España en una o más de las localizaciones estudiadas fue de 29,35%. La prevalencia de artrosis-cervical fue del 10,10% y de artrosis-lumbar del 15,52%. Ambas son más frecuentes en mujeres y a mayor edad, así como en personas con niveles de estudios bajos y obesidad. La prevalencia de artrosis de cadera fue del 5,13% y la de artrosis de rodilla del 13,83%; estas se asocian con el sexo femenino, sobrepeso y obesidad, menor frecuencia en nivel de estudios alto y con la edad. La prevalencia de la artrosis de mano fue del 7,73%. Es más frecuente en mujeres, obesas, con bajo nivel de estudios y mayor edad. Conclusiones. El estudio EPISER2016 es el primero que analiza la prevalencia de artrosis sintomática en 5 localizaciones (columna cervical, lumbar, rodilla, cadera y manos) en España. La artrosis de la columna lumbar es la más prevalente. [Abstract] Introduction. The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). Objective. To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. Material and methods. Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. Results. The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. Conclusion. The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent.

[Resumen] Introducción. La Sociedad Española de Reumatología elaboró en el año 2000 el estudio EPISER2000 para conocer la prevalencia de la artrosis y otras enfermedades reumáticas en España. Los cambios sociodemográficos y en los hábitos de vida ocurridos en los últimos años en España justifican actualizar los datos de las enfermedades reumáticas (EPISER2016). Objetivo. Estimar la prevalencia de artrosis sintomática de columna cervical, columna lumbar, cadera, rodilla y mano, en población adulta en España. Material y métodos. Estudio transversal de base poblacional. Se realizó un muestreo aleatorizado polietápico estratificado y por conglomerados. Los participantes fueron contactados por teléfono para cumplimentar un cuestionario de cribado de artrosis. El reumatólogo confirmaba o descartaba el diagnóstico. Se utilizaron los criterios-clínicos-ACR para diagnosticar artrosis de manos y los criterios clínico-radiológicos-ACR para diagnosticar la artrosis de rodilla y cadera. Resultados. La prevalencia de artrosis en España en una o más de las localizaciones estudiadas fue de 29,35%. La prevalencia de artrosis-cervical fue del 10,10% y de artrosis-lumbar del 15,52%. Ambas son más frecuentes en mujeres y a mayor edad, así como en personas con niveles de estudios bajos y obesidad. La prevalencia de artrosis de cadera fue del 5,13% y la de artrosis de rodilla del 13,83%; estas se asocian con el sexo femenino, sobrepeso y obesidad, menor frecuencia en nivel de estudios alto y con la edad. La prevalencia de la artrosis de mano fue del 7,73%. Es más frecuente en mujeres, obesas, con bajo nivel de estudios y mayor edad. Conclusiones. El estudio EPISER2016 es el primero que analiza la prevalencia de artrosis sintomática en 5 localizaciones (columna cervical, lumbar, rodilla, cadera y manos) en España. La artrosis de la columna lumbar es la más prevalente. [Abstract] Introduction. The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). Objective. To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. Material and methods. Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. Results. The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. Conclusion. The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent. EPISER2016 ha sido financiado por Celgene, Laboratorios, Gebro Pharma, Merck Sharp and Dohme de España, Pfizer y Sanofi-Aventis. Los financiadores no han intervenido en el diseño del estudio, recogida ni análisis de datos, ni en la redacción de este artículo. IRP yMS fueron financiados con programas Miguel Servet II y Contrato Río Hortega-Fondo de Investigación Sanitaria (CPII17/00026 y CM17/00101), respectivamente. El Fondo de Investigación Sanitaria, integrado en el Plan Nacional de Programa Científico, Desarrollo e Innovación Tecnológica 2013-2016, es financiado por el ISCIII-Subdirección General de Evaluación y Promoción de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) «Una forma de hacer Europa»

Diagnosis of latent tuberculosis infection in patients with immune-mediated inflammatory chronic diseases (IMIDs) can be challenged as diagnostic test reliability could be impaired by immunosuppression. We retrospectively analyzed the Quantiferon Gold-Test in-Tube (QFT-G-IT) results of all patients with IMIDs seen at the Department of Internal Medicine of Son Llatzer Hospital, Palma de Mallorca (Spain), looking for the factors related to QFT-G-IT indeterminate results. During the study period (2008–2015), 520 patients met the inclusion criteria. Factors associated with indeterminate QFT-G-IT results in a univariate analysis were inflammatory bowel disease, disease activity, lymphopenia, and medium-to-high doses of corticosteroids. In a subsequent multivariate analysis, only lymphopenia (defined as

The prevalence of fibromyalgia (FM) differs depending on the population studied. The main objective of the EPISER2016 study was to estimate the prevalence of FM in adults in Spain. The secondary objective was to evaluate the association with sociodemographic and anthropometric characteristics and smoking.This is a population-based cross-sectional multicentre study. The random selection was based on multistage stratified cluster sampling. The final sample comprised 4916 persons aged ≥20 years. Participants were contacted by telephone for completion of a screening survey. Investigating rheumatologists evaluated positive results (review of medical records and/or telephone interview, with medical visit if needed) to confirm the diagnosis. Prevalence and 95% confidence interval were calculated, taking into account the sample design. Weighing was applied based on age, sex, and geographic origin. Predictive models were constructed to analyse which sociodemographic, anthropometric and lifestyle variables in the call centre questionnaire were associated with the presence of FM.602 subjects (12.25%) had a positive screening result for FM, of which 24 were missing (3.99%). A total of 141 cases of FM were recorded. The estimated prevalence was 2.45% (95% CI, 2.06-2.90). Female sex was the variable most associated with FM, with an odds ratio (OR) of 10.156 (95% CI, 5.068-20.352). Peak prevalence was at 60-69 years (p=0.009, OR=6.962). FM was 68% more frequent in obese individuals (OR, 1.689; 95% CI, 1.036-2.755).The prevalence of FM in adults in Spain barely changed between 2000 and 2016 and it is similar to that observed in Europe as a whole.

Aim: To describe the methodology of the EPISER 2016 (study of the prevalence of rheumatic diseases in adult population in Spain), as well its strengths and limitations. The aim of this study is to estimate the prevalence of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), osteoarthritis (knee, hip, hands, and cervical and lumbar spine), fibromyalgia, gout and clinical osteoporotic fracture. Material and method: Population-based, multicenter, cross-sectional study, with the participation of 45 municipalities in the 17 Spanish autonomous communities. The reference population will consist of adults aged 20 years and over residing in Spain. A computer-assisted telephone interview (CATI) system will be used for data collection. Diagnostic suspicions and diagnoses received by the participants will be studied by rheumatologists in the referral hospitals in the selected municipalities. Statistical analysis: the prevalence of the rheumatic diseases will be calculated using estimators and their 95% confidence intervals. Weights will be calculated in each of the sampling stages in accordance with the probability of selection. The distribution of the population in Spain will be obtained from the Spanish Statistics Institute. Conclusions: Sociodemographic and lifestyle changes over the last 16 years justify EPISER 2016. This study will provide current data about the prevalences of RA, AS, PsA, SLE, SS, osteoarthritis, fibromyalgia, gout and clinical osteoporotic fracture. The results will allow comparisons with studies from other countries and EPISER 2000. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Reumatologia y Colegio Mexicano de Reumatologia. All rights reserved.

Background:Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 2 out of 3 Rheumatoid Arthritis patients. Identifying the patients that will not respond to this therapeutic approach is a major translational goal in RA. Association of seropositivity to rheumatoid factor (RF) or anti-cyclic-citrullinated antibodies (anti-CCP) with anti-TNF response has proven inconclusive, suggesting that other yet unexplored biomarkers could be more informative for this goal.Objectives:We tested the association of two recently introduced biomarkers in RA: anti-carbamylated protein antibodies (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4).Methods:A prospective cohort of n=80 RA patients starting anti-TNF therapy was recruited and levels for all four autoantibodies -RF, anti-CCP, anti-CarP and anti-PAD4- were measured at baseline. The change in DAS28 score between baseline and week 12 of therapy was used as the clinical endpoint.Results:Single marker-analysis showed no significant association with drug response. However, when testing for interactions between autoantibodies, we found highly significant associations with drug response. Anti-CCP and RF showed a positive interaction with the response to anti-TNF therapy (P=0.00068), and anti-PAD4 and antiCarP titers showed a negative interaction with the clinical response at week 12 (P=0.0062). Using an independent retrospective sample (n=199 patients), we validated the interaction between anti-CCP and RF with the clinical response to anti-TNF agents. (P=0.044).Conclusion:The results of this study show that interactions between antibodies are important in the response to anti-TNF therapy and suggest potential pathogenic relationships.Acknowledgments :We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaborationDisclosure of Interests:Antonio Julià: None declared, Maria Lopez Lasanta: None declared, Francisco Blanco: None declared, Antonio Gómez: None declared, Isabel Haro: None declared, Antonio Juan Mas: None declared, Alba Erra: None declared, Mª Luz García Vivar: None declared, Jordi Monfort: None declared, Simon Sánchez Fernandez: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Mercedes Alperi-López: None declared, Raúl Castellanos: None declared, Antonio Fernandez-Nebro: None declared, Cesar Diaz Torne: None declared, Núria Palau: None declared, Raquel M Lastra: None declared, Jordi Lladós: None declared, Raimon Sanmarti: None declared, Sara Marsal: None declared

To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD).Analysis of data after 2.5 years of follow-up from the prospective study CARMA project, that includes patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and matched individuals without CIRD from 67 hospitals in Spain. CVE cumulative incidence per 1000 patients was calculated after 2.5 years from the start of the project. Weibull proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) of the risk factors.2595 (89.1%) patients completed the 2.5 years of follow-up visit. Cumulative incidence of CVE in patients with CIRD was 15.30 cases per 1000 patients (95% CI: 12.93-17.67), being higher in the subgroup with AS; 22.03 (95% CI: 11.01-33.04). Patients with AS (HR: 4.11; 95% CI: 1.07-15.79), those with older age (HR: 1.09; 95% CI: 1.05-1.13), systolic hypertension (HR: 1.02; 95% CI: 1.00-1.04) and long duration of the disease (HR: 1.07; 95% CI: 1.03-1.12) were at higher risk of first CVE during the 2.5 years of follow-up. In contrast, female gender was a protective factor (HR: 0.43; 95% CI: 0.18-1.00).Among CIRD patients prospectively followed-up at rheumatology outpatient clinics, those with AS show higher risk of first CVE. Besides cardiovascular risk factors, such as hypertension, being a man and older as well as having a long disease duration increase the risk of CVE in patients with CIRD.

Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients.A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA.The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence.In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us.

Resumen Objetivo Establecer las caracteristicas diferenciales segun el sexo y el tiempo de evolucion de la enfermedad en aquellos pacientes diagnosticados de espondilitis anquilosante (EA) asistidos en consultas de reumatologia de toda Espana, incluidos en el Registro Espanol de Espondiloartritis (REGISPONSER), asi como la repercusion diagnostica y terapeutica que ello conlleva. Pacientes y metodos Estudio transversal y observacional de 1.514 pacientes con EA seleccionados de entre 2.367 con espondiloartritis incluidos en REGISPONSER. En cada paciente se evaluaron y registraron de modo exhaustivo los datos demograficos, epidemiologicos, sociosanitarios, clinicos, analiticos, radiologicos y terapeuticos previstos en el protocolo de REGISPONSER que componen el Conjunto Minimo Basico que identifica la enfermedad. La funcion fisica se evaluo mediante «Bath Ankylosing Spondylitis Functional Index». La actividad clinica mediante velocidad de sedimentacion globular, proteina C reactiva y «Bath Ankylosing Spondylitis Disease Activity Index» (BASDAI). A cada paciente se le realizaron radiografias anteroposterior de pelvis, anteroposterior y lateral de columna lumbar y lateral de columna cervical, y se puntuaron segun el indice «Bath Ankylosing Spondylitis Radiographic Index Spine» (BASRI-Spine), que mide el dano estructural. Resultados De los 1.514 pacientes seleccionados, 1.131 (74.7%) eran hombres. Encontramos que existen diferencias significativas en la edad tanto al inicio de los sintomas como en el dia de la inclusion entre ambos grupos, siendo menor en los hombres. Tambien obtuvimos diferencias en el tiempo de evolucion de la enfermedad, que fue menor en el grupo de las mujeres. En cuanto a la existencia de antecedentes de EA entre los familiares de primer grado, las formas familiares fueron mas frecuentes entre las mujeres, tambien resulto superior en estas la puntuacion media del BASDAI, con independencia del tiempo de evolucion. Por el contrario, la mejoria del dolor con la toma de antiinflamatorios no esteroideos fue mayor en el caso de los hombres, asi como la severidad radiologica, ambas de forma significativa. Conclusiones Entre los pacientes con EA espanoles existen algunas diferencias en las manifestaciones clinicas y cuando se controlo segun el tiempo de evolucion, tambien encontramos diferencias radiologicas segun el sexo; los hombres muestran mas dano estructural, mientras que las mujeres presentan mayor actividad. Estos datos sugieren que el fenotipo de EA difiere entre generos, lo que puede influir en el manejo diagnostico y posterior eleccion terapeutica.

Quantiferon-TB-Gold in Tube(®) test (QFT-G-IT) may have advantages if combined with TST when screening for Latent Tuberculosis Infection (LTBI) prior to initiating anti-TNF therapy in an area of intermediate tuberculosis incidence such as Spain. In a small-scale prospective study, we evaluate the use of QFT-G-IT in combination with the screening recommended in Spain (Tuberculin-Skin Test, TST retest, clinical data, and Chest X-Ray (CXR)) for LTBI in patients considered as candidates for anti-TNFα treatment.From June 2008 to October 2010, 123 patients from a 300-bed hospital in Palma de Mallorca (Spain) were included in the study. The majority of patients were under immunosuppressive therapy. A positive TST and TST booster were found in 22 and 17 patients, respectively. Thus 39 (31.7%) of the 123 patients had a positive TST. QFT-G-IT was positive in 16 patients (13.6%), indeterminate in 4 (3.2%), and negative in 103 (83.7%). One of the two tests was positive and LTBI was diagnosed in 34.1% of patients. The agreement between TST and QFT-G-IT among vaccinated patients was low and not statistically significant (Kappa=0.15) and was almost perfect among non-BCG vaccinated patients (K=0.81). TST positive responses were significantly related to BCG-vaccination (p0.05) and QFT-G-IT positive response rates were related to older age (p0.05).QFT-G-IT may have advantages when combined with TST in immunosuppressed patients especially in older patients with a negative TST; in BCG vaccinated patients with a positive TST, QFT-G-IT could avoid unnecessary treatments and toxicities related to a false-positive TST result.

Objective To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44-joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent. Methods A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated. Results A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44-joint count and index for synovitis and PD signal and the 12-joint count and index for synovitis and PD signal at baseline and 6 months (r = 0.84–0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables. Conclusion A 12-joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.

Resume L'arthrose erosive est une maladie essentiellement feminine consideree comme rare. Elle se localise habituellement aux articulations interphalangiennes des mains. Toutefois, elle a ete rapportee dans quelques cas a la hanche, a l'epaule ou au pied. Nous rapportons ici les observations d'un homme et d'une femme atteints d'une arthrose erosive des pieds.

To describe the differential characteristics by gender and time since disease onset in patients diagnosed with ankylosing spondylitis (AS) attending the Spanish rheumatology clinics, including those on the "Spanish Registry of spondyloarthritis" (REGISPONSER), as well as the diagnostic and therapeutic implications that this entails.This is a transversal and observational study of 1514 patients with AS selected from 2367 spondyloarthritis cases included in REGISPONSER. For each patient, the demographics, epidemiology, geriatric, clinical, laboratory, radiological, and therapeutic aspects were were evaluated and comprehensively recorded under the aegis of REGISPONSER, constituting the Minimum Basic identifying data for the disease. Physical function was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI). Clinical activity was evaluated using erythrocyte sedimentation rate, C reactive protein and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Each patient underwent pelvic anteroposterior, anteroposterior and lateral lumbar spine as well as lateral cervical spine x rays; they were scored according to the Bath Ankylosing Spondylitis Spine Radiographic Index, which measures structural damage.Of the 1514 patients screened, 1131 (74.7%) were men. We found significant differences in age at onset of symptoms as well as in the day of inclusion, between the two groups, being lower in men. We also obtained differences in the duration of the disease, which was lower in women. As for the existence of a history of AS among first-degree relatives, family forms were more common among women. The mean BASDAI score was also higher in women, regardless of time since onset of disease. In contrast, the improvement of pain with the use of NSAID's and radiological severity were higher in men, both reaching statistical significance.Among the Spanish AS patients, there are some differences in the clinical manifestations, even when the time since onset of disease was controlled; we also found radiological differences by gender; men showing more structural damage, while women were more active. These data suggest that the phenotype of AS differs between genders. This can influence the subsequent diagnostic approach and therapeutic decisions.

Background Adult-onset Still’s disease (AOSD) is often refractory to standard immunosuppressive therapy. Tocilizumab (TCZ) has shown efficacy in isolated cases or in small series. Objectives We assess the efficacy of TCZ in AOSD. Methods Multicenter study of 27 patients with AOSD of 18 hospitals diagnosed according to Yamagouchi’s criteria (J Rheumatol 1992;19:424). TCZ was used due to lack of good response to standard therapy or to other biologic agents. Results The 27 patients (20 women/ 7 men), had a mean age of 37.2±15.9 (range 16-71) and an average duration of AOSD of 5.9±4.6 years (range 0.1-17) to onset of TCZ. Prior to the onset of TCZ and besides corticosteroids, patients had recived the following drugs: Metotrexate (26 patients), Anakinra (12), Etanercept (6), Adalimumab (5) and Infliximab (3). TCZ standard dose was 8 mg/k/iv/4 weeks. At TCZ onset, the most frequent clinical manifestations were joint (27 cases), cutaneous (14) and fever (18), along with analytical abnomalities, increase of ESR or CRP (20 cases), anemia (11) or leukocytosis (15). Clinical and analytical improvement was observed soon, 1 st month after the onset of TCZ therapy (TABLE). After a mean follow-up of 20.8±12 months, cutaneous manifestations disappeared in 13 of 14 patients (92,9%), fever in 17 of 18 (94.4%) and joint manifestation in 22 of 27 (81,5%). Improvement of analytical abnormalities was observed in most cases with normalization of the blood cell count in 9 of 15 (60%) patients, anemia in 11 of 11 (100%), ESR in 15 of 19 (78.9 % ), CRP in 17 of 20 (85%), hepatic enzymes (AST/ALT) in 3 of 4 (50 %) and ferritin seric levels in 11 of 13 (84,6%). The median [IQR] dose of steroids was reduced from 15 [8.8-25] to 5 [1.3-7.5]. Conclusions In refractory AOSD, TCZ yields early and maintained clinical-analytical response, even in refractory cases to other biological agents. Although TCZ showed global efficacy, joint are more refractory than other systemic manifestations. Disclosure of Interest None Declared