Prevalence of Sjogren's syndrome in the general adult population in Spain: estimating the proportion of undiagnosed cases

To estimate the prevalence of Sjogren's syndrome (SS) in the adult Spanish population we performed a population-based multicenter cross-sectional study. Cases were defined by the American-European Consensus Group criteria proposed in 2002. A total of 4,916 subjects aged 20 years or over were included. The estimated prevalence of SS (including primary and secondary forms) in the adult population in Spain was 0.33% (95% CI 0.21-0.53). Extrapolating to the total population of the country aged >= 20 years (around 37.7 million persons), there would be around 125,000 cases of SS in Spain. Considering only primary SS, the estimated prevalence was 0.25% (95% CI 0.15-0.43) or 1 person in 400. The prevalence of primary SS in Spain is comparable to that reported in other European studies with a similar design and diagnostic criteria. Based on these results, primary SS could not be considered a rare (orphan) disease. Only 50% of cases had already been diagnosed with SS prior EPISER 2016 study, confirming the existence of a non-negligible proportion of undiagnosed cases in the general population

Recomendaciones de experto sobre el bloqueo de la interleucina 6 en pacientes con artritis reumatoide

[Abstract] Objective: To draft recommendations on interleukin 6 (IL-6) blockade in rheumatoid arthritis (RA), based on best evidence and experience. Methods: A group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators formulated 23 questions about IL-6 blockade (indications, efficacy, safety, etc.). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results: The 8 preliminary recommendations were accepted after the Delphi process. They covered aspects such as the use of these therapies in monotherapy, in combination, in patients with refractory disease or intolerant patients, response evaluation, optimization and risk management. Conclusions: The manuscript aims to solve frequently asked questions and aid in decision making strategies when treating RA patients with IL-6 blockade.[Resumen] Objetivo. Generar recomendaciones sobre el bloqueo de la interleucina 6 (IL-6) en pacientes con artritis reumatoide (AR), basadas en la mejor evidencia y experiencia. Métodos. Se seleccionó a 10 expertos reumatólogos en el manejo de los inhibidores de la IL-6. Los 2 coordinadores generaron 23 preguntas sobre el bloqueo de la IL-6 en la AR (perfiles de indicación, eficacia, seguridad, etc.) para ser contestadas mediante una revisión sistemática de la literatura. Con base en las preguntas se definieron los criterios de inclusión y exclusión, y las estrategias de búsqueda (para interrogar Medline, Embase y la Cochrane Library). Dos revisores seleccionaron los artículos resultantes de la búsqueda. Se generaron tablas de evidencia. Paralelamente, se evaluaron abstracts de congresos de EULAR y ACR. Con toda esta evidencia los coordinadores propusieron 8 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunión de grupo nominal con el resto de los expertos. Para cada recomendación se estableció el nivel de evidencia y grado de recomendación, y el grado de acuerdo mediante un Delphi. Se definió acuerdo si al menos el 80% de los participantes contestaban sí a la recomendación (sí o no). Resultados. Las 8 recomendaciones preliminares se aceptaron tras el Delphi. Abarcan aspectos como su uso en monoterapia, en combinación, en pacientes refractarios o intolerantes, la evaluación de su respuesta, la optimización o la gestión del riesgo. Conclusiones. Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones con el bloqueo de la IL-6 en el manejo de la AR

Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis

Objective: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. Methods: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. Results: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). Conclusions: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.This research is supported by the Research Unit of the Spanish Society of Rheumatology. BIOBADASER is supported by the Spanish Agency of Drugs and Medical Devices (AEMPS), Biogen, Bristol-Myers and Squibb (BMS), Celltrion, Janssen, Lilly, Merck Sharp and Dohme (MSD), Novartis, Pfizer, Regeneron, and Samsung Bioepis.S

Prevalence of Symptomatic Osteoarthritis in Spain: EPISER2016 Study

[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

Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis

Background: B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. Methods: Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. Results: B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. Conclusions: These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium

Prevalence of Systemic Lupus Erythematosus in Spain: Higher than Previously Reported in other Countries?

[Abstract] Objectives: Prevalence of SLE varies among studies, being influenced by study design, geographical area and ethnicity. Data about the prevalence of SLE in Spain are scarce. In the EPISER2016 study, promoted by the Spanish Society of Rheumatology, the prevalence estimate of SLE in the general adult population in Spain has been updated and its association with sociodemographic, anthropometric and lifestyle variables has been explored. Methods: Population-based multicentre cross-sectional study, with multistage stratified and cluster random sampling. Participants were contacted by telephone to carry out a questionnaire for the screening of SLE. Investigating rheumatologists evaluated positive results (review of medical records and/or telephone interview, with medical visit if needed) to confirm the diagnosis. To calculate the prevalence and its 95% CI, the sample design was taken into account and weighing was calculated considering age, sex and geographic origin. Multivariate logistic regression models were defined to analyse which sociodemographic, anthropometric and lifestyle variables included in the telephone questionnaire were associated with the presence of SLE. Results: 4916 subjects aged 20 years or over were included. 16.52% (812/4916) had a positive screening result for SLE. 12 cases of SLE were detected. The estimated prevalence was 0.21% (95% CI: 0.11, 0.40). SLE was more prevalent in the rural municipalities, with an odds ratio (OR) = 4.041 (95% CI: 1.216, 13.424). Conclusion: The estimated prevalence of SLE in Spain is higher than that described in most international epidemiological studies, but lower than that observed in ethnic minorities in the United States or the United Kingdom

Prevalence of Symptomatic Axial Osteoarthritis Phenotypes in Spain and Associated Socio-Demographic, Anthropometric, and Lifestyle Variables

Epidemiology of RMDFinanciado 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

Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time

Association between severity of periodontitis and clinical activity in rheumatoid arthritis patients: a case–control study

Abstract Background A high prevalence of periodontitis has been reported in rheumatoid arthritis (RA) patients, although the strength of this association, its temporal link and the possible relationship between the severity of periodontitis and RA disease activity remain unclear. The objective of this work was to investigate whether periodontitis is associated with RA and whether periodontitis severity is linked to RA disease activity. Methods This case–control study included 187 patients diagnosed with RA and 157 control patients without inflammatory joint disease. RA disease activity and severity were evaluated by the Disease Activity Score 28, the Simplified Disease Activity Index, the Clinical Disease Activity Index, rheumatoid factor, anti-citrullinated protein antibody titers, the erythrocyte sedimentation rate, C-reactive protein, presence of extra-articular manifestations and type of RA therapy. Exposure severity was assessed by the following periodontal parameters: plaque index, bleeding on probing, probing pocket depth and clinical attachment levels. Sociodemographic variables and comorbidities were evaluated as confounding variables. Outcome and exposure variables were compared by both parametric and nonparametric tests, and possible associations were assessed through regression analysis with a calculation for the adjusted odds ratio (OR). Results A significant association was demonstrated between periodontitis and RA with an adjusted OR of 20.57 (95% CI 6.02–70.27, p < 0.001). Compared with controls, all parameters related to periodontal status (plaque index, bleeding on probing, probing pocket depth and clinical attachment levels) were significantly worse in RA patients (p < 0.001). Periodontitis severity was significantly associated with RA disease activity (p < 0.001), showing in an ordinal logistic regression model an association between periodontal severity and disease activity with an adjusted OR of 2.66 (95% CI 1.24–5.74, p = 0.012). Conclusion A significant association was demonstrated between periodontitis and RA, independent of other confounders. This association was more evident in patients with pronounced periodontal disease and higher RA disease activity