Search

Objective: To describe the prevalence of sarcopenia in rheumatoid arthritis (RA) patients aged ≥65 years and identify the risk factors associated with sarcopenia. Methods: This is a multicenter, controlled, cross-sectional study of 76 RA patients and 76 age- and sex-matched healthy controls. Sarcopenia was defined according to the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Whole-body dual-energy X-ray absorptiometry (DXA) was performed. Binary regression was used to assess the relationship between sarcopenia and sex, age, duration of RA, Mini Nutritional Assessment (MNA) score, and Short Physical Performance Battery (SPPB) score in patients with RA. Results: Nearly 80% of participants were female, and the average age was >70 years. Patients with RA had lower muscle mass and greater adiposity (fat-to-muscle ratio mean [SD] 0.9 [0.2] vs. 0.8 [0.2]; p = 0.017) than controls, mainly in the central area (android/gynoid ratio, median [p25–p75]: 1.0 [0.9–1.2] vs. 0.9 [0.8–1.1]; p < 0.001). Twelve patients (15.8%) and three controls (3.9%) had confirmed sarcopenia (p = 0.014). Sarcopenic obesity was observed in 8/76 patients with RA (10.5%) and in 1/76 controls (1.3%) (p = 0.016). The factors associated with sarcopenia were male sex (OR [95% CI]: 9.3 [1.1–80.4]; p = 0.042), disease duration (OR [95% CI]: 1.1 [1.0–1.2]; p = 0.012), and nutritional status according to the MNA (OR [95% CI]: 0.7 [0.5–0.9]; p = 0.042). Conclusions: Our results suggest that patients with RA aged ≥65 years may be at increased risk for sarcopenia, adiposity, and malnutrition (especially male patients with long-standing disease) and have poor nutritional status.

Objective To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. Patients and methods Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n = 79) or Enbrel® (n = 59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52 weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. Results No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95% CI] at 12.0 months [10.2-12.0] for the biosimilar and 12.0 months [12.0-12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52 weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55 € (1,747.20 €/patient-years) for the hospital. Conclusion The biosimilar Benepali is as effective and safe as the original and much more cost-effective.

Objective To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. Patients and methods Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n = 79) or Enbrel® (n = 59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52 weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. Results No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95% CI] at 12.0 months [10.2–12.0] for the biosimilar and 12.0 months [12.0–12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52 weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55 € (1,747.20 €/patient-years) for the hospital. Conclusion The biosimilar Benepali is as effective and safe as the original and much more cost-effective.

A human motion capture system using an RGB-D camera could be a good option to understand the trunk limitations in spondyloarthritis. The aim of this study is to validate a human motion capture system using an RGB-D camera to analyse trunk movement limitations in spondyloarthritis patients. Cross-sectional study was performed where spondyloarthritis patients were diagnosed with a rheumatologist. The RGB-D camera analysed the kinematics of each participant during seven functional tasks based on rheumatologic assessment. The OpenNI2 library collected the depth data, the NiTE2 middleware detected a virtual skeleton and the MRPT library recorded the trunk positions. The gold standard was registered using an inertial measurement unit. The outcome variables were angular displacement, angular velocity and lineal acceleration of the trunk. Criterion validity and the reliability were calculated. Seventeen subjects (54.35 (11.75) years) were measured. The Bending task obtained moderate results in validity (r = 0.55–0.62) and successful results in reliability (ICC = 0.80–0.88) and validity and reliability of angular kinematic results in Chair task were moderate and (r = 0.60–0.74, ICC = 0.61–0.72). The kinematic results in Timed Up and Go test were less consistent. The RGB-D camera was documented to be a reliable tool to assess the movement limitations in spondyloarthritis depending on the functional tasks: Bending task. Chair task needs further research and the TUG analysis was not validated. Graphical abstract Comparation of both systems, required software for camera analysis, outcomes and final results of validity and reliability of each test.

This study aimed to evaluate the role of microRNAs (miRNA) as biomarkers of treatment response in rheumatoid arthritis (RA) patients through a systematic review of the literature. The MEDLINE and Embase databases were searched for studies including RA-diagnosed patients treated with disease-modifying antirheumatic drugs (DMARDs) that identify miRNAs as response predictors. Review inclusion criteria were met by 10 studies. The main outcome of the study was the response to treatment, defined according to EULAR criteria. A total of 839 RA patients and 67 healthy donors were included in the selected studies. RA patients presented seropositivity for the rheumatoid factor of 74.7% and anti-citrullinated C-peptide antibodies of 63.6%. After revision, 15 miRNAs were described as treatment response biomarkers for methotrexate, anti-tumour necrosis factor (TNF), and rituximab. Among treatments, methotrexate presented the highest number of predictor miRNAs: miR-16, miR-22, miR-132, miR-146a and miR-155. The most polyvalent miRNAs were miR-146a, predicting response to methotrexate and anti-TNF, and miR-125b, which predicts response to infliximab and rituximab. Our data support the role of miRNAs as biomarkers of treatment response in RA and point to DMARDs modifying the miRNAs expression. Nevertheless, further studies are needed since a meta-analysis that allows definitive conclusions is not possible due to the lack of studies in this field.

BACKGROUND/OBJECTIVES Immune-mediated inflammatory diseases (IMIDs) are prevalent diseases. There is, however, a lack of understanding of the link between diet and IMIDs, how much dietary patterns vary between them and if there are food groups associated with a worsening of the disease. SUBJECTS/METHODS To answer these questions we analyzed a nation-wide cohort of n = 11,308 patients from six prevalent IMIDs and 2050 healthy controls. We compared their weekly intake of the major food categories, and used a Mendelian randomization approach to determine which dietary changes are caused by disease. Within each IMID, we analyzed the association between food frequency and disease severity. RESULTS After quality control, n = 11,230 recruited individuals were used in this study. We found that diet is profoundly altered in all IMIDs: at least three food categories are significantly altered in each disease (P

Objectives To study the differences between rheumatoid arthritis (RA)-interstitial lung disease (ILD) patients and RA patients without ILD in severity markers and disease activity and to identify factors associated with the presence of ILD in RA patients. Patients and methods Patients: RA-ILD patients selected from a multicentre cohort in Andalusia, Spain. Controls: RA-patients without ILD paired by sex, age and disease duration. Protocol: RA patients are reviewed every 3–6 months in rheumatology consultation. All patients are reviewed according to a predetermined protocol with systematic data collection. Outcomes: description of ILD type, differences in severity markers and disease activity in both groups. Other variables: ILD type by imaging technique (HRCT): nonspecific interstitial pneumonia (NSIP)/usual interstitial pneumonia (UIP). Lung function by PTF. Activity and severity markers of arthritis by DAS28-ESR, HAQ, RF, ACPA and erosions. Treatment with DMARD. Statistical analysis: descriptive and paired T-test or Chi-square test followed by binary logistic regression (DV: ILD in patients with RA). Results Eighty-two patients were included, 41 RA-ILD and 41 RA controls. RF and ACPA positivity, serositis and osteoporosis were more frequent in RA-ILD patients. No significant differences in DAS28 were observed (P = .145) between RA-ILD and RA control patients. RA-ILD patients presented worse HAQ scores (P = .006). All patients were treated with disease modifying antirheumatic drugs (DMARDs). The risk of developing ILD in RA patients is tripled by a history of smoking or the presence of erosive arthritis (R2 = .36). Conclusions The results of our study support the higher frequency of UIP and NSIP in RA patients. DLCO is the most sensitive parameter to detect ILD in RA patients. Our study showed that ILD in RA patients was associated with RA severity (presence of erosions and ACPA) and with a history of smoking.

Resumen Objetivos Estudiar las diferencias en pacientes con artritis reumatoide (AR) y enfermedad pulmonar intersticial (EPID) y pacientes con AR sin EPID, e identificar factores asociados con la EPID en pacientes con AR. Pacientes y metodos Estudio observacional de casos y controles. Pacientes: se seleccionaron pacientes de una cohorte con AR y EPID de diferentes centros de Andalucia. Controles: pacientes con AR sin EPID pareados por edad, genero y tiempo de evolucion. Protocolo: los pacientes con AR se revisan cada 3-6 meses en consulta. Todos los pacientes son revisados de acuerdo con un protocolo predeterminado con recogida de datos sistematica. Desenlaces: descripcion del tipo radiologico de EPID, diferencias en los marcadores de gravedad en casos y controles y en la actividad de la enfermedad. Otras variables: descripcion del tipo de EPID por TACAR: neumonia intersticial usual (NIU), neumonia intersticial no especifica (NINE) y de la funcion pulmonar por PFR; marcadores de actividad y gravedad de artritis: DAS28, HAQ, FR, ACPA, erosiones. Tratamiento con FAME. Analisis: descriptivo, χ2 o t de Student, seguida de regresion logistica binaria (Vd:EPID en pacientes con AR). Resultados Se incluyeron 82 pacientes: 41 con AR y EPID y 41 controles AR sin EPID. Los pacientes con EPID presentaron un mayor porcentaje de pacientes con FR y ACPA positivos y una mayor frecuencia de serositis y osteoporosis. No hubo diferencias significativas en DAS28 en casos y controles(p = 0,145), pero los pacientes de AR con EPID presentaron peor HAQ (p = 0,006). Todos los pacientes estaban en tratamiento con FAME. El analisis multivariante mostro que los pacientes con AR exfumadores y con artritis erosiva triplicaron el riesgo de presentar EPID (R2 = 0,36). Conclusiones Los resultados de nuestro estudio apoyan la mayor frecuencia de NIU y NINE en pacientes con AR, asi como la alteracion de DLCO como el parametro mas importante. Los pacientes con AR y EPID se asociaron con una enfermedad mas grave (erosiones y ACPA) y con el tabaco.

Objective: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD). Methods: We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. Results: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2–42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03–3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70–0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72–0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. Conclusion: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution computed tomography (HRCT) PATIENTS AND METHODS: We performed a cross-sectional, observational study in patients with RA-ILD (cases) controlled with a group of RA patients without ILD (controls) paired by sex, age, and time of disease evolution. Patients were assessed using HRCT, PFT, and US. The main variables were B-line number, evaluation of the lung-US score already described, pleural irregularities, and A pattern US lost. ROC curve analysis was performed to establish the cut-off point of the US B-lines number for detecting the presence of significant RA-ILD in relation to HRCT, and logistic regression analysis was performed to identify the intercostal spaces.Seventy-one patients were included, 35 (49.2%) with ILD-RA and 36 (50.8%) RA controls. Regarding US score, we found that the detection of 5.5 lines in a reduced score of 8 intercostal spaces had a sensitivity = 62.2%, specificity = 91.3%, PPV = 88.4%, and NPV = 69.5%. In multivariate analysis, the intercostal spaces which showed independent association with ILD were 3rd right anterior axillary space (OR [IC 95%] 19.0 [1.3-27.5]), 8th right posterior axillary space (OR [IC 95%] 0.04 [0.0-0.6]), 8th right subscapular space (OR [IC 95%] 16.5 [1.8-45.5]), 9th right paravertebral space (OR [IC 95%] 7.11 [1.0-37.1]), and 2nd left clavicular middle space (OR [IC 95%] 21.9 [1.26-37.8]).Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. A 8-space reduced score showed a similar total predictive capacity than 72-space score. Key Points • Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. • The 72-space evaluation is highly sensitive, whereas a simplified score enables a more specific and faster diagnosis. • The number of B lines is correlated with DLCO, ACPA, inflammatory activity, and physical function.

Background Studies in axial spondyloarthritis (AxSp) have shown that intensity of pain, anxiety, depression and inflammatory activity are associated with poor sleep quality. Aim To describe mood and sleep disorders and positive psychological factors in patients with AxSp and psoriatic arthritis (PsA) and to evaluate the psychological factors that are potentially involved in sleep disorders. Design Multicenter cross-sectional observational study based on a series of patients with AxSp and PsA. Participants Participants were selected consecutively from patients aged ≥18 years with AxSp or PsA followed at the rheumatology department of 4 Spanish hospitals. Inclusion criteria age ≥18 years, AxSp (ASAS criteria) or PsA (CASPAR criteria), ability to understand the study and prepared to complete the questionnaires. Methods Main outcomes: Oviedo Sleep Quality questionnaire result. Secondary outcomes psychological status evaluated using the Hospital Anxiety and Depression Scale (HADS) questionnaire, health-related quality of life evaluated using SF-36, perception of pain evaluated using the short questionnaire for assessment of pain (BDU) and fatigue evaluated using the Fatigue Scale (FACIT) questionnaire. We performed a descriptive multivariate linear regression analysis to study factors that were independently associated with sleep disorders. The STROBE guidelines were adopted. Results We included 301 patients (152 [50.5%] with AxSp and 149 [49.5%] with PsA). The multivariate linear regression analysis for the whole sample showed that insomnia was inversely associated with emotional recovery and biologic disease-modifying antirheumatic drugs and directly associated with depression in both groups. The analysis by disease (AxSp and PsA) showed that insomnia was independently associated with depression and emotional recovery. Conclusions Insomnia may be associated with other mood disorders, quality of life and inflammatory activity in the patients studied here. Relevance to clinical practice A nurse intervention can be carried out to prevent sleep disorders knowing the consequences and triggers of the problem.

Objectives To describe the therapeutic management of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) in patients initiating treatment with biological agents. Materials and methods Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analysed. Results Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS. Conclusions Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments.

OBJECTIVE To evaluate cognitive function in adult patients with juvenile idiopathic arthritis (JIA) and associated factors. PATIENTS AND METHODS We performed a cross-sectional observational study of adult patients with JIA and a healthy control group (no inflammatory diseases) matched for age, gender, and educational level. Cognitive function was assessed using Wechsler Adult Intelligence Scale-III. The cognitive domains measured were attention/concentration, verbal function, visuospatial organization, working memory, and problem solving (Similarities). Other measures included clinical-epidemiological characteristics, comorbid conditions, and treatment. We performed a descriptive bivariate analysis and logistic regression to identify factors associated with visuospatial involvement. RESULTS The study population comprised 104 subjects (52 with JIA and 52 healthy controls). Patients with JIA had poorer results for visuospatial function, with a lower median scaled score on the Block Design test (5.0 [4.0-8.0] vs 8.0 [5.0-10.0]; P = .014). The number of patients with scaled scores below the average range (

Objective To describe the frequency of polyautoimmunity and multiple autoimmune syndrome in patients with rheumatoid arthritis (RA) and patients with systemic lupus erythematosus (SLE). Patients and methods This was a cross-sectional observational study of patients with RA, SLE, and controls without autoimmune rheumatic disease. Cases were those with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and SLE according to the 2019 American College of Rheumatology/European League Against Rheumatism criteria, consecutively recruited in a rheumatology clinic. Controls were subjects with no rheumatic autoimmune disease (AIDs) recruited in the same area. Patients filled out a questionnaire on polyautoimmunity. Variables of interest were polyautoimmunity (RA or SLE with other AIDs), whereas secondary variables were rheumatic, skin, endocrine, digestive, and neurological AIDs. Multiple autoimmune syndrome is defined as the presence of 3 or more AIDs and a family history of AIDs. Statistical analyses performed were descriptive, bivariate, and multivariate (dependent variable: polyautoimmunity). Results The study population comprised 109 patients with RA, 105 patients with SLE, and 88 controls. Polyautoimmunity was recorded in 15 patients with RA (13.8%), 43 with SLE (41%), and 2 controls (2.2%). The most frequent AID in RA was Sjogren syndrome (53.3%), followed by Hashimoto thyroiditis and psoriasis; the most frequent AIDs in SLE were Sjogren syndrome (55.8%) and antiphospholipid syndrome (30.2%), followed by Hashimoto thyroiditis. Obesity was associated with polyautoimmunity in RA (odds ratio [OR], 3.362; p = 0.034). In SLE, joint damage (OR, 2.282; p = 0.038) and anti-RNP antibodies (OR, 5.095; p = 0.028) were risk factors for polyautoimmunity, and hydroxychloroquine was a protective factor (OR, 0.190; p = 0.004). Conclusions Polyautoimmunity is frequent in RA and even more frequent in SLE. It was associated with obesity in RA and with joint damage and anti-RNP in SLE. Hydroxychloroquine was a protector.

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. Metodos Se selecciono a 10 expertos reumatologos 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 indicacion, eficacia, seguridad, etc.) para ser contestadas mediante una revision sistematica de la literatura. Con base en las preguntas se definieron los criterios de inclusion y exclusion, y las estrategias de busqueda (para interrogar Medline, Embase y la Cochrane Library). Dos revisores seleccionaron los articulos resultantes de la busqueda. 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 reunion de grupo nominal con el resto de los expertos. Para cada recomendacion se establecio el nivel de evidencia y grado de recomendacion, y el grado de acuerdo mediante un Delphi. Se definio acuerdo si al menos el 80% de los participantes contestaban si a la recomendacion (si o no). Resultados Las 8 recomendaciones preliminares se aceptaron tras el Delphi. Abarcan aspectos como su uso en monoterapia, en combinacion, en pacientes refractarios o intolerantes, la evaluacion de su respuesta, la optimizacion o la gestion del riesgo. Conclusiones Este documento pretende resolver algunos interrogantes clinicos habituales y facilitar la toma de decisiones con el bloqueo de la IL-6 en el manejo de la AR.

To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD).We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was changed in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD.After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%).Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non-anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening. Key Points • We have performed prospectively evaluated lung and joint function in patients with RA-ILD receiving treatment with various DMARDs. • In our study, the lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. • Neither csDMARDs nor anti-TNF agents were associated with a significant risk of worsening of lung disease, whereas non-anti-TNF bDMARDs could reduce the risk of worsening of lung disease. • Smoking and poor control of joint involvement were the main factors associated with worsening of lung disease.

Objectives: To describe the frequency of COVID-19 and the effect of vaccination in patients with interstitial lung disease and systemic autoimmune disease (ILD-SAD) and to identify factors associated with infection and severity of COVID-19. Methods: We performed a cross-sectional multicenter study of patients with ILD-SAD followed between June and October 2021. The main variable was COVID-19 infection confirmed by a positive polymerase chain reaction (PCR) result for SARS-CoV-2. The secondary variables included severity of COVID-19, if the patient had to be admitted to hospital or died of the disease, and vaccination status. Other variables included clinical and treatment characteristics, pulmonary function and high-resolution computed tomography. Two logistic regression was performed to explore factors associated with “COVID-19” and “severe COVID-19”. Results: We included 176 patients with ILD-SAD: 105 (59.7%) had rheumatoid arthritis, 49 (27.8%) systemic sclerosis, and 22 (12.54%) inflammatory myopathies. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/22 (13.22%) died. As to the vaccination, 163/176 (92.6%) patients received the complete doses. The factors associated with SARS-CoV-2 infection were FVC (OR (95% CI), 0.971 (0.946–0.989); p = 0.040), vaccination (OR (95% CI), 0.169 (0.030–0.570); p = 0.004), and rituximab (OR (95% CI), 3.490 (1.129–6.100); p = 0.029). The factors associated with severe COVID-19 were the protective effect of the vaccine (OR (95% CI), 0.024 (0.004–0.170); p < 0.001) and diabetes mellitus (OR (95% CI), 4.923 (1.508–19.097); p = 0.018). Conclusions: Around 13% of patients with ILD-SAD had SARS-CoV-2 infection, which was severe in approximately one-third. Most patients with severe infection were not fully vaccinated.

This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case–control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. The study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR (p = 0.032) and HAQ values (p = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17–5.22]; p = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24–6.78]; p = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00–1.12]; p = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00–1.06]; p = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00–1.00]; p = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07–1.46]; p = 0.004). Our data support that the inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD.

Objectives To assess the characteristics and risk of lymphoma in a large cohort of patients with SLE. Methods A case–cohort analysis was performed within a dynamic cohort of SLE patients from the Spanish Society of Rheumatology Lupus Registry (RELESSER). Clinical and analytical features were compared between the lymphoma SLE group and the control SLE group using an independent-sample Student’s t-test or Mann–Whitney test for continuous variables and the χ2 test for categorical variables with Fisher’s exact test if necessary. The multivariate analysis was based on a generalized linear model. Results Twenty-one patients with SLE and lymphoma and 3965 non-lymphoma controls with SLE were studied. Most lymphomas were of B cell origin (n = 15/21), with diffuse large B cell lymphoma being the most frequent histological type (8/21, 38.1%). As in the general population, the risk of lymphoma in SLE was higher in male than in female patients and increased with age. In the lymphoma SLE group, bivariate analysis showed a significantly higher percentage of pericarditis, organic brain syndrome, seizures, vasculitis, haemolytic anaemia, splenomegaly, venous thrombosis and mean modified (excluding lymphoma) SLICC/ACR damage index. In contrast, renal involvement, positive anti-dsDNA, and antimalarials ever were less frequent. Conclusions In this large multicentre Spanish cohort, we identified characteristics of SLE that are associated with a higher risk of lymphoma. Antimalarials were significantly negatively associated with risk of lymphoma in SLE patients. Nevertheless, further prospective studies are needed to clarify these findings.

Background/objectives: Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. Methods: Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. Results: The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p < 0.0001), cardiac arrhythmia (7.38 [4.00-13.42], p < 0.0001), pulmonary hypertension (3.71 [1.84-7.25], p < 0.0002), valvulopathy (6.33 [3.41-11.62], p < 0.0001), non-cardiovascular damage (1.29 [1.16-1.44], p < 0.000) and calcium/vitamin D treatment (5.29 [2.07-16.86], p = 0.0015). Female sex (0.46 [0.25-0.88], p = 0.0147) and antimalarials (0.28 [0.17-0.45], p < 0.000) proved to be protective factors. Conclusions: Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect. (c) 2021 Published by Elsevier Inc.

Objectives: To compare the ability to participate in social activities among rheumatoid arthritis patients with other rheumatic disease patients and identify potentially implicated factors. Patients and methods: Between June and November 2019, we consecutively selected patients aged ≥18 years with RA (defined according to ACR/EULAR 2010), SpA (ASAS/EULAR 2010), and SLE (ACR 1997). Main outcome measures: Ability to participate in social roles and activities evaluated using the PROMIS score v2.0 short-form 8a (PROMIS-APS). Secondary outcomes: Participation in social activities according to a series of variables (mobility, depression, satisfaction with social relationships, social isolation, company, emotional support, instrumental support, and support via information). We evaluated the association between the ability to participate in social activities and associated variables using multivariable linear regression analysis. Results: The study population comprised 50 patients with RA (33.1%), 51 patients (33.8%) with SpA, and 50 patients (33.1%) with SLE. The mean PROMIS-APS scores were similar in the three groups. The multivariable analysis for the whole sample showed that the ability to participate in social activities was inversely associated with depression and directly with social satisfaction, mobility, company, and age. The stratified analysis revealed an inverse association between inflammatory activity and ability to participate in social activities in patients with RA and SpA, but not in those with SLE. Conclusion: All patients with RA, SpA, and SLE had a similar ability to participate in social activities. This was associated with other psychosocial factors (social satisfaction, mobility, company, depression) and clinical factors (age and inflammatory activity).

To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity.Nested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD.The final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03-3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05-1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01-1.35]; p = 0.027), anti-citrullinated peptide antibody (OR [95% CI] 1.23 [1.14-13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96-0.99]; p = 0.036).In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

Objectives: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. Patients and methods: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) &gt, 10% or diffusing capacity of the lungs for carbon monoxide &gt, 15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. Results: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8–93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3–2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0–2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4–3.9]), and smoking (HR, 2.7 [95%CI, 1.6–4.7]). Conclusion: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.

Objective Sarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective of this post hoc analysis was to compare the efficacy of sarilumab (200 mg every 2 weeks) monotherapy (MONARCH study) with that of sarilumab and MTX combination therapy (MOBILITY study) at week 24. Methods The endpoints assessed were mean change from baseline in the Clinical Disease Activity Index (CDAI), 28-joint Disease Activity using CRP (DAS28-CRP), CRP, haemoglobin (Hb), pain visual analogue scale (VAS) and Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue. Least square (LS) mean change from baseline (95% CI) at week 24 for all endpoints was compared between the treatment arms for adjusted comparisons. Results This analysis included 184 patients on sarilumab monotherapy and 399 patients on sarilumab plus MTX. Differences (P Conclusion This analysis demonstrated that the efficacy of sarilumab monotherapy was similar to that of sarilumab and MTX combination therapy.

espanolObjetivo Revisar la eficacia y seguridad del rituximab en neuropatia vasculitica (NV). Metodos Se realizo una busqueda en la literatura de Medline y Embase hasta 2017. Los terminos incluidos guardaron relacion con «vasculitis», «neuropatia vasculitica» y «rituximab». Dicha busqueda fue realizada por 2 revisores. El resultado principal fue la eficacia del rituximab. Resultados Tras seleccionar inicialmente 702 articulos, 5 de ellos permanecieron con un nivel de evidencia de entre 1+ y 3, y un grado de recomendacion variable. En el unico ensayo clinico incluido, el rituximab fue superior a la terapia convencional para vasculitis crioglobulinemica, mostrando NV un incremento en la tasa de retencion farmacologica (64,3 vs. 3,5%; p Conclusiones Rituximab parece ser un tratamiento eficaz y seguro para NV, en el contexto de vasculitis crioglobulinemica. Se carece de evidencia sobre la eficacia especifica de NV en el contexto de otras vasculitis. EnglishObjective To review the efficacy and safety of rituximab in vasculitic neuropathy (VN). Methods A literature search was performed on Medline and Embase up until 2017. It included terms related to “vasculitis”,“vasculitic neuropathy” and “Rituximab”. Research was carried out by two reviewers. The main outcome was rituximab efficacy. Results Of an initial selection of 702 articles, 5 remained with a level of evidence between 1+ and 3 and variable recommendation degree. In the only clinical trial included, rituximab was superior to conventional therapy for cryoglobulinemic vasculitis with VN showing an increase in drug retention rate (64.3% vs. 3.5%; P Conclusions Rituximab seems an effective and safe treatment for VN in the context of cryoglobulinemic vasculitis. Evidence for specific efficacy in VN in the context of other types of vasculitis is lacking.

Objective: To identify factors associated with the higher proportion of fatty tissue and overweight/obesity observed in patients with juvenile idiopathic arthritis (JIA). Patients and methods: We performed a cross-sectional study of 80 JIA patients aged 4–15 years with 80 age- and sex-matched healthy controls. Body composition was assessed using dual-energy x-ray absorptiometry. The 27-joint Juvenile Arthritis Disease Activity score (JADAS27) was calculated. Two multivariate models were constructed to identify factors associated with overweight/obesity and fat mass index (FMI). Results: No differences were found between cases and controls in body mass index (BMI) or body composition. However, compared with controls, patients with a high inflammatory activity (JADAS27 &gt, 4.2 for oligoarticular JIA or &gt, 8.5 for polyarticular disease) had higher values for BMI (p = 0.006), total fat mass (p = 0.003), FMI (p = 0.001), and fat in the legs (p = 0.001), trunk (p = 0.001), and arms (p = 0.002). The factors associated with overweight/obesity in patients were the duration of therapy with biological drugs, measured in months (OR [95% CI] = 1.12 [1.02–1.04], p = 0.037), and physical activity (OR [95% CI] = 0.214 [0.07–0.68], p = 0.010), while the factors associated with FMI were age (β [95% CI] = 0.30 [0.17–1.41], p = 0.014), JADAS27 (β [95% CI] = 0.45 [0.16–1.08], p = 0.009), and physical activity (β [95% CI] = −0.22 [−5.76 to 0.29], p = 0.031). Conclusion: Our study revealed no differences between JIA patients with well-controlled disease and low disability and the healthy population in BMI or body composition. Furthermore, the association observed between inflammatory activity and adiposity could be responsible for poorer clinical course.

To evaluate the effectiveness and safety of tocilizumab (TCZ) monotherapy in biologic-naïve patients with rheumatoid arthritis (RA) versus patients with previous biologic exposure in a real-world setting.Non-controlled clinical-trial, 32-week prospective multicenter study including RA patients with moderate-severe disease activity starting TCZ in monotherapy who had a prior inadequate response or were intolerant to methotrexate (MTX). Effectiveness according to EULAR response evaluated at 24-week and safety at 32-weekwere assessed.Of the 93 were enrolled of whom 84 (90%) were eligible for the effectiveness analysis. Biologic-naïve patients (n=46, 54.8%) were younger (51.5 versus 57.9) with shorter disease duration (6.4 versus 13.3) but presented similar comorbidities in comparison with non-naïve patients. DAS28 remission was achieved in a higher percentage in the group of patients with prior biological treatment. 89 adverse events (AE) were recorded in 50 patients, most of them non-serious AE (non-SAE) (86.3%).In a real world setting, TCZ exhibit similar effectiveness and safety in monotherapy in patients with RA regardless previous exposure to other biologic therapies. This study provides additional and valuable real-world findings on the use of TCZ in patients with RA.

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.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients.Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions.Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort.Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

Resumen OBJETIVO: Describir si las enfermedades inflamatorias reumaticas (EIR) se asocian con mayor riesgo de hospitalizacion y/o mortalidad por COVID-19 e identificar los factores asociados a la hospitalizacion y mortalidad en EIR y COVID-19 en diferentes Hospitales de Andalucia METODOS: Diseno: Estudio multicentrico observacional de casos y controles Pacientes: Casos: EIR y COVID-19 de diferentes centros de Andalucia Controles: pacientes sin EIR pareados por sexo, edad y PCR-COVID Protocolo: se solicito al servicio de microbiologia un listado de pacientes con PCR para COVID-19 desde 14 de marzo al 14 de abril de 2020 Se identificaron los pacientes que tuvieran EIR y luego consecutivamente un control pareado para cada caso Variables: La variable de desenlace principal fue ingreso hospitalario y mortalidad por COVID-19 Analisis estadistico: bivariante seguida de modelos de regresion logistica binaria (Vd : mortalidad/ingreso hospitalario) RESULTADOS: Se incluyeron 156 pacientes con COVID-19, 78 con EIR y 78 sin EIR Los pacientes con EIR no presentaron caracteristicas de la enfermedad COVID-19 diferentes a la poblacion general, tampoco mayor ingreso hospitalario ni mortalidad El factor asociado con mortalidad en los pacientes con EIR fue edad (OR [IC 95%], 1,1 [1,0-1,2];p=0,025), mientras que los factores asociados a ingreso hospitalario fueron edad (OR [IC 95%], 1,1 [1,1-1,2];p=0,007) e hipertension arterial (OR [IC 95%], 3,9 [1,5-6,7];p=0,003) CONCLUSION: La mortalidad y el ingreso hospitalario por COVID-19 no parecen aumentados en las EIR La edad se asocio con mortalidad en EIR y, ademas, la hipertension arterial se asocio con ingreso hospitalario ABSTRACT OBJECTIVE: To describe whether rheumatic inflammatory diseases (RID) are associated with a higher risk of hospitalization and / or mortality from COVID-19 and identify the factors associated with hospitalization and mortality in RID and COVID-19 in different Hospitals in Andalusia METHODS: Design: Multicentre observational case-control study Patients: RID and COVID-19 from different centres in Andalusia Controls: patients without RIS matched by sex, age and CRP-COVID Protocol: a list of patients with PCR for COVID-19 was requested from the microbiology service from March 14 to April 14, 2020 The patients who had RID were identified and then consecutively a paired control for each case Variables: The main outcome variable was hospital admission and mortality from COVID-19 Statistical analysis: bivariate followed by binary logistic regression models (DV: mortality / hospital admission) RESULTS: One hundred and fifty-six patients were included, 78 with RID and COVID-19 and 78 without RID with COVID-19 The patients did not present characteristics of COVID-19 disease different from the general population, nor did they present higher hospital admission or mortality The factor associated with mortality in patients with RID was advanced age (OR [95% CI], 1 1 [1 0-1 2];p = 025), while the factors associated with hospitalization were advanced age (OR [95% CI], 1 1 [1 0-1 1];p = 007) and hypertension (OR [95% CI], 3 9 [1 5-6 7] ;p = 003) CONCLUSION: Mortality and hospital admission due to COVID-19 do not seem to increase in RID Advanced age was associated with mortality in RID and, in addition, HTN was associated with hospital admission

Objective: To prospectively evaluate possible decline of cognitive functions in adult patients with juvenile idiopathic arthritis (JIA) and identify associated factors. Patients and methods: We performed a 24-month prospective observational study of adults (≥16 years) with JIA. The primary outcome measure was decline in cognitive function defined as a worsening of ≥2 points on the scales of the subsets administered to evaluate the different cognitive areas using the Wechsler Adult Intelligence Scale (WAIS) after 24 months: attention/concentration (digit span); verbal function (vocabulary); visual-spatial organization (block design); working memory (letter-number sequencing); and problem solving (similarities). Other variables included average inflammatory activity using C-reactive protein and composite activity indexes, comorbidity, and treatment. Logistic regression was performed to identify factors associated with cognitive decline. Results: The study population comprised 52 patients with JIA. Of these, 15 (28.8%) had cognitive decline at V24. The most affected functions were working memory (17.3%), attention/concentration (9.6%), verbal function (7.7%), visual-spatial organization (7.7%), and problem solving (3.8%). There were no significant differences in the median direct or scale scores for the cognitive functions evaluated between V0 and V24 for the whole sample. The factors associated with cognitive decline in patients with JIA were average C-reactive protein (OR [95% CI], 1.377 [1.060–1.921]; p = 0.039), depression (OR [95% CI], 3.691 [1.294–10.534]; p = 0.015), and treatment with biologics (OR [95% CI], 0.188 [0.039–0.998]; p = 0.046). Conclusion: Cognitive decline was detected in almost one third of adults with JIA after 24 months of follow-up. Systemic inflammatory activity in JIA patients was related to cognitive decline. Patients treated with biologics had a lower risk of decline in cognitive functions.

ObjectivesTo describe the prevalence of insulin resistance (IR) in patients with established rheumatoid arthritis (RA) and to analyse the contribution of cumulative inflammatory burden and other factors to its development.DesignObservational cross-sectional study.ParticipantsPatients with RA and controls matched for age, sex and Body Mass Index. We excluded patients with diabetes.SettingsPatients from an RA inception cohort at Hospital Regional Universitario de Málaga, Spain, were recruited between September 2016 and May 2018.Primary and secondary outcome measuresIR was evaluated using the homeostasis model assessment for IR and beta-cell function and the quantitative insulin sensitivity check index. Other variables included the cumulative 28-Joint Disease Activity Score (DAS28) with C reactive protein (CRP) body composition and cytokines. Two logistic regression models were constructed to identify factors associated with IR in patients with RA.ResultsEighty-nine patients with RA and 80 controls were included. The prevalence of IR was similar in both cases and controls. Inflammatory activity was controlled appropriately in patients during follow-up (mean DAS28 3.1 (0.8)). The presence of IR in patients with RA was associated with obesity (OR 6.01, 95% CI 1.9 to 8.7), higher cumulative DAS28-CRP values during follow-up (OR 2.8, 95% CI 1.3 to 6.0), and higher interleukin-1β levels (OR 1.6, 95% CI 1.1 to 2.4). The second model showed that the risk of IR increased by 10% for each kilogram of excess body fat.ConclusionIn patients with well-controlled, established RA, IR is associated mainly with poorer control of inflammation from diagnosis and with obesity, specifically total fat mass.

Objective The aim of the present study was to describe the demographic, clinical and immunological characteristics of patients with late-onset (≥50 years) SLE vs patients with early-onset SLE ( Methods We performed a cross-sectional retrospective study of 3619 patients from the RELESSER database (National Register of Patients with Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). Results A total of 565 patients (15.6%) were classified as late-onset SLE and 3054 (84.4%) as early-onset SLE. The male-to-female ratio was 5:1. Mean (s.d.) age at diagnosis in the late-onset group was 57.4 (10.4) years. At diagnosis, patients with late-onset SLE had more comorbid conditions than patients with early-onset SLE; the most frequent was cardiovascular disease (P Conclusion Late-onset SLE is insidious, with unusual clinical manifestations that can lead to diagnostic errors. Clinical course is generally indolent. Compared with early-onset disease, activity is generally reduced and immunosuppressants are less commonly used. Long-term prospective studies are necessary to determine whether the causes of death are associated with clinical course or with age-associated comorbidities in this population.

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.