Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry.

OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Interstitial Lung Disease Is Associated with Sleep Disorders in Rheumatoid Arthritis Patients.

OBJECTIVE: To evaluate sleep disorders and associated factors in patients with rheumatoid-arthritis-associated interstitial lung disease (RA-ILD). METHODS: We performed an observational study of 35 patients with RA-ILD (cases) and 35 age- and sex-matched RA patients without ILD (controls). We evaluated sleep disorders (Oviedo Sleep Questionnaire), positive psychological factors (resilience using the Wagnild and Young Resilience Scale, emotional intelligence using the 24-item Trait Meta-Mood Scale), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (36-item short-form survey), and fatigue (Functional Assessment of Chronic Illness Therapy Questionnaire). Other variables studied included the Charlson Comorbidity Index (CCI) and RA activity according to the DAS28-ESR. RESULTS: Compared to the controls, the cases were characterized by poorer sleep quality with a higher prevalence of insomnia (42% vs. 20%; p = 0.039), greater severity of insomnia (p = 0.001), and lower sleep satisfaction (p = 0.033). They also had poorer resilience and emotional recovery and more severe anxiety and depression. A diagnosis of ILD was the only factor independently associated with the three dimensions of sleep quality. The predictors of poorer sleep satisfaction in patients with RA-ILD were age (ß = -0.379), DAS28-ESR (ß = -0.331), and usual interstitial pneumonia pattern (ß = -0.438). The predictors of insomnia were DAS28-ESR (ß = 0.294), resilience (ß = -0.352), and CCI (ß = 0.377). CONCLUSIONS: RA-ILD is associated with significant sleep disorders. RA-ILD seems to be an independent risk factor for sleep alterations, with a greater impact on insomnia. Age, disease activity, and comorbidity also play a role in sleep disorders in patients with RA-ILD.

Prevalence of Malnutrition and Associated Factors in Older Patients with Rheumatoid Arthritis: A Cross-Sectional Study.

OBJECTIVE: To describe the frequency of malnutrition in older patients with rheumatoid arthritis (RA) and investigate associated risk factors. METHODS: This multicenter, cross-sectional study included participants aged ≥65 years who met the 2010 ACR/EULAR criteria for RA. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF) and based on variables, such as albumin level, the Geriatric Nutritional Risk Index (GNRI), and vitamin D. Data were also collected on epidemiological variables, inflammatory disease activity, quality of life, physical function, and frailty. Multivariate models were used to study factors associated with nutritional status. RESULTS: The study population comprised 76 RA patients aged ≥65 years, of whom 68.4% had a normal nutritional status, and 31.5% had an impaired nutritional status: 28.9% were at risk of malnutrition, and 2.6% were malnourished. Additionally, 10% had albumin levels <3.8 g/L. Patients with impaired nutritional status had poorer quality of life and physical function. The factors associated with compromised nutritional status (OR [95% CI]) were age (1.0 [1.0-1.1]; p = 0.035), DAS28-ESR (1.8 [1.0-3.2]; p = 0.024), and EuroQoL-5D-5L (0.9 [0.9-0.9]; p = 0.040). Furthermore, the GNRI was associated with the MNA score (0.06 [0.0-0.1]; p = 0.014). CONCLUSIONS: Approximately one-third of older patients with RA have impaired nutritional status. Older age, higher inflammatory disease activity, and decreased quality of life are associated with impaired nutritional status. The MNA and GNRI are valuable tools for assessing the nutritional status of patients with RA.

Pregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER).

INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.

Sarcopenia and Nutrition in Elderly Rheumatoid Arthritis Patients: A Cross-Sectional Study to Determine Prevalence and Risk Factors.

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.

Inflammatory Biomarkers in the Diagnosis and Prognosis of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

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.

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study.

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.

Adiposity is associated with expansion of the genus Dialister in rheumatoid arthritis patients.

OBJECTIVE: To analyze the intestinal microbiota of patients with rheumatoid arthritis (RA) and obesity and a higher percentage of fatty tissue. METHODS: Nested case-control study of 80 RA patients and 80 age and sex-matched controls. Obesity was defined as a body mass index ≥ 30, and body composition using dual-energy x-ray absorptiometry. The gut microbiota was analyzed using 16 S rRNA gene sequencing; bioinformatics analysis was performed using QIIME2 and PICRUSt. Other variables included averaged 28-joint Disease Activity Score (DAS28-ESR), cytokines and adipokines. Two multivariate were constructed with obesity and fat mass index (FMI). RESULTS: Obesity was more frequent in RA patients than in controls (36.3 % vs 25.1 %; p = 0.026), as was a higher FMI value (mean [SE]=11.6 [3.9] vs 10.2 [3.9]; p = 0.032). Alpha and beta diversity analysis revealed differences in gut microbiota between RA patients with and without obesity. Dialister and Odoribacter were more abundant in RA patients with obesity than in RA patients without obesity, while the genus Clostridium was more abundant in RA patients without obesity. The factors associated with obesity in RA patients were age (OR [95 % CI], 1.09 [1.02-1.17]), mean DAS28-ESR (OR [95 % CI], 1.46 [1.12-1.67]), leptin levels (OR [95 % CI], 1.06 [1.01-1.10]), the genus Dialister (OR [95 % CI], 1.03 [1.01-1.07]), and the genus Clostridium (OR [95 % CI], 0.013 [0.00-0.36]). The associations observed for FMI were similar. CONCLUSIONS: In patients with RA, obesity, and a higher percentage of fatty tissue, intestinal microbiota differed from that of controls and of the other patients. The genus Dialister was associated with obesity and FMI.

Analysis of comorbidity in rheumatoid arthritis-associated interstitial lung disease: a nested case-cohort study.

OBJECTIVES: To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity. METHODS: 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. RESULTS: 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). CONCLUSION: In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

miRNA-Mediated Epigenetic Regulation of Treatment Response in RA Patients-A Systematic Review.

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.

Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study.

Objectives: To describe the characteristics of patients between late-onset rheumatoid arthritis (LORA) with young-onset (YORA), and analyze their association with cumulative inflammatory burden. Methods: We performed a nested cohort study in a prospective cohort comprising 110 patients with rheumatoid arthritis (RA) and 110 age- and sex-matched controls. The main variable was cumulative inflammatory activity according to the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). High activity was defined as DAS28 ≥ 3.2 and low activity as DAS28 < 3.2. The other variables recorded were inflammatory cytokines, physical function, and comorbid conditions. Two multivariate models were run to identify factors associated with cumulative inflammatory activity. Results: A total of 22/110 patients (20%) met the criteria for LORA (≥ 60 years). Patients with LORA more frequently had comorbid conditions than patients with YORA and controls. Compared with YORA patients, more LORA patients had cumulative high inflammatory activity from onset [13 (59%) vs. 28 (31%); p = 0.018] and high values for CRP (p = 0.039) and IL-6 (p = 0.045). Cumulative high inflammatory activity in patients with RA was associated with LORA [OR (95% CI) 4.69 (1.49-10.71); p = 0.008], smoking [OR (95% CI) 2.07 (1.13-3.78); p = 0.017], anti-citrullinated peptide antibody [OR (95% CI) 3.24 (1.15-9.13); p = 0.025], average Health Assessment Questionnaire (HAQ) score [OR (95% CI) 2.09 (1.03-14.23); p = 0.034], and physical activity [OR (95% CI) 0.99 (0.99-0.99); p = 0.010]. The second model revealed similar associations with inflammatory activity in patients with LORA. Conclusion: Control of inflammation after diagnosis is poorer and comorbidity more frequent in patients with LORA than in YORA patients and healthy controls.

Relación entre poliautoinmunidad y obesidad sarcopénica en pacientes con artritis reumatoide / Relationship between polyautoimmunity and sarcopenic obesity in rheumatoid arthritis patients

Objetivo: Analizar si la poliautoinmunidad en los pacientes con artritis reumatoide (AR) se asocia con sarcopenia y alteraciones de la composición corporal total. Métodos: Estudio observacional transversal de una serie de casos de pacientes con AR, reclutados consecutivamente de la consulta de reumatología. Se evaluó la composición corporal mediante absorciometria de rayos X de energia dual (DXA). Las variables de interés fueron la poliautoinmunidad (AR asociada a otras enfermedades autoinmunes), sarcopenia, masa grasa e índice de masa corporal. Otras variables incluidas fueron clínico-analíticas y citoquinas inflamatorias y adipoquinas. La relación entre obesidad sarcopénica y la presencia de poliautoinmunidad se estudió mediante análisis multivariable. Resultados: De los 94 pacientes con AR incluidos en el estudio, 15 (16%) tenían poliautoinmunidad. Un total de 23 (24,5%) pacientes con AR presentaron sarcopenia, la cual fue más prevalente en los pacientes con poliautoinmunidad en comparación con los demás (46,7 vs. 20,3%; p = 0,029). La sarcopenia no se asoció con el contenido corporal de grasa en la composición corporal (p = 0,870) ni con el índice de masa corporal (IMC) (p = 0,998). En el análisis multivariante, los factores asociados a la poliautoinmunidad en AR fueron la sarcopenia (odds ratio [IC 95%], 4,80 [1,49- 13,95]), el IMC (1,18 [1,04-1,35]), y la resistina (1,249 [1,01-1,53]). Conclusión: Los pacientes con AR con poliautoinmunidad mostraron una mayor prevalencia de sarcopenia y obesidad, además tuvieron valores más elevados de resistina en comparación con pacientes con AR sin poliautoinmunidad.(AU)

Objective: Sarcopenia is a major cause of morbidity in rheumatoid arthritis patients. Our purpose was to determine whether polyautoimmunity is associated with sarcopenia and alterations in whole body composition in patients with rheumatoid arthritis (RA). Methods: We performed a cross-sectional observational study of a series of cases of RA. All patients were recruited consecutively from a rheumatology clinic. Body composition by dual-energy x-ray absorptiometry (DEXA) was assessed. The variables of interest were polyautoimmunity (RA associated with other autoimmune diseases), sarcopenia, fat mass, and body mass index (BMI). Other variables included were clinical-analytical and inflammatory cytokines and adipokines. The relationship between sarcopenic obesity and the presence of polyautoimmunity was studied using multivariate analysis. Results: Of the 94 patients with RA included in the study, 15 (16%) had polyautoimmunity. A total of 23 patients with RA (24.5%) had sarcopenia, which was more prevalent in patients with polyautoimmunity than in patients without polyautoimmunity (46.7% vs 20.3%; p = .029). Sarcopenia was not associated with body fat content (p = .870) or with BMI (p = .998). The multivariate analysis showed the factors associated with polyautoimmunity in RA to be sarcopenia (odds ratio [95% CI], 4.80 [1.49-13.95]), BMI (1.18 [1.04-1.35]), and resistin (1.249 [1.01-1.53]). Conclusión: Sarcopenia and obesity were more prevalent in patients with RA and polyautoimmunity. Resistin values were also higher in this group than in patients with RA without polyautoimmunity.(AU)

Collinsella is associated with cumulative inflammatory burden in an established rheumatoid arthritis cohort.

OBJECTIVE: To analyze the gut microbiota of patients with rheumatoid arthritis (RA) according to disease activity. METHODS: An observational cross-sectional study of 110 patients with RA and 110 age- and sex-matched controls was performed. Patients were classified according to the disease activity (DAS28 ≥3.2 or DAS28 <3.2). Clinical and epidemiological variables were included. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics analysis based on QIIME and PICRUSt. A multivariate analysis was performed to identify factors associated with inflammatory activity. RESULTS: The mean DAS28 indicated remission/low inflammatory activity in 71 patients (64.5 %) and moderate/high activity in 39 (35.5 %) during follow-up. Alpha and beta diversity analysis revealed differences in gut microbiota between the 3 study groups. In the moderate/high activity RA, we observed a significant change in the abundance of genera compared with the other groups. The abundance of Collinsella and Bifidobacterium was increased in RA patients compared with controls. The metabolic profile of gut microbiota was characterized by differences in pathways related to Biosynthesis, Generation of Precursor Metabolites/Energy, and Degradation/Utilization/Assimilation between the 3 groups. The factors associated with cumulative inflammatory activity in RA were age (OR [95 % CI], 1.065 [1.002-1.131]), obesity (OR [95% CI], 3.829 [1.064-8.785]), HAQ score (OR [95% CI], 2.729 [1.240-5.009]), and expansion of the genus Collinsella (OR [95% CI], 3.000 [1.754-9.940]). CONCLUSIONS: The composition of gut microbiota differed between patients with RA and moderate/high activity, patients with remission/low activity, and controls. The genus Collinsella, age, obesity, and physical function were associated with cumulative inflammatory burden in RA.

Hospitalizaciones y mortalidad por COVID-19 en pacientes con enfermedades inflamatorias reumáticas en Andalucía / Hospitalization and Mortality from COVID-19 of Patients with Rheumatic Inflammatory Diseases in Andalusia

Objetivo: Describir si las enfermedades inflamatorias reumáticas (EIR) se asocian con mayor riesgo de hospitalización y/o mortalidad por COVID-19 e identificar los factores asociados a la hospitalización y mortalidad en EIR y COVID-19 en diferentes hospitales de Andalucía.Métodos: Diseño: Estudio multicéntrico observacional de casos y controles.Pacientes Casos: EIR y COVID-19 de diferentes centros de Andalucía. Controles: pacientes sin EIR pareados por sexo, edad y PCR-COVID.Protocolo: Se solicitó al Servicio de Microbiología 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. Análisis estadístico Bivariante seguida de modelos de regresión logística binaria (variable dependiente: mortalidad/ingreso hospitalario).Resultados: Se incluyeron 156 pacientes con COVID-19, 78 con EIR y 78 sin EIR. Los pacientes con EIR no presentaron características de la enfermedad COVID-19 diferentes a la población 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 con ingreso hospitalario fueron edad (OR [IC 95%], 1,1 [1,1-1,2]; p = 0,007) e hipertensión arterial (OR [IC 95%], 3,9 [1,5-6,7]; p = 0,003).Conclusión: La mortalidad y el ingreso hospitalario por COVID-19 no parecen aumentados en las EIR. La edad se asoció con mortalidad en EIR y, además, la hipertensión arterial se asoció con ingreso hospitalario.(AU)

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 = 0.025), while the factors associated with hospitalization were advanced age (OR [95% CI], 1.1 [1.0-1.1]; p = 0.007) and hypertension (OR [95% CI], 3.9 [1.5-6.7]; p = 0.003).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.(AU)

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease.

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.

Longitudinal Study of Cognitive Functioning in Adults with Juvenile Idiopathic Arthritis.

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.

Importance of Vaccination against SARS-CoV-2 in Patients with Interstitial Lung Disease Associated with Systemic Autoimmune 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.

Systematic Review and Metaanalysis of Worldwide Incidence and Prevalence of Antineutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis.

Objective: In this study, we aimed to evaluate the worldwide incidence and prevalence of ANCA-associated vasculitis (AAV). Methods: A systematic search of Medline and Embase was conducted until June 2020 for studies that analyzed the incidence and prevalence of patients aged >16 years diagnosed with AAV in different geographical areas. A meta-analysis was undertaken to estimate the pooled incidence per million person-years and prevalence per million persons in AAV overall and for each subtype of AAV: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The 95% confidence interval (CI) and I2 for heterogeneity were calculated. Results: The meta-analysis included 25 studies that met the inclusion criteria and covered a total of 4547 patients with AAV. Frequency increased over time. The global pooled incidence (95% CI) was 17.2 per million person-years (13.3−21.6) and the global pooled prevalence (95% CI) was 198.0 per million persons (187.0−210.0). The pooled incidence per million person-years for each AAV subtype varied from highest to lowest, as follows: GPA, 9.0; MPA, 5.9; and EGPA, 1.7. The individual pooled prevalence per million persons was, as follows: GPA, 96.8; MPA, 39.2; and EGPA, 15.6. AAV was more predominant in the northern hemisphere. By continent, a higher incidence in America and pooled prevalence of AAV was observed in America and Europe. Conclusion: The pooled incidence and prevalence of AAV seem to be increasing over time and are higher in the case of GPA. AAV was generally more frequent (incidence and prevalence) in the northern hemisphere.