Cardiovascular Events, Malignancies, and Efficacy Outcomes in Latin American Patients With Rheumatoid Arthritis Receiving Tofacitinib or Tumor Necrosis Factor Inhibitors: A Post Hoc Analysis of the ORAL Surveillance Study.

BACKGROUND/OBJECTIVE: To assess safety/efficacy of tofacitinib and tumor necrosis factor inhibitors (TNFi) in patients from Latin America (LATAM) in ORAL Surveillance. METHODS: In ORAL Surveillance, 4362 patients with rheumatoid arthritis aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily or TNFi. This post hoc analysis stratified patients by geographical location (LATAM, n = 1202; non-LATAM, n = 3160). Incidence rates (IRs; patients with first event/100 patient-years) and hazard ratios for adverse events of special interest were reported. Efficacy outcomes included Clinical Disease Activity Index and American College of Rheumatology 20/50/70 responses. RESULTS: Risk factors associated with cardiovascular disease and malignancies were less prevalent in the LATAM cohort compared with the non-LATAM cohort. IRs for patients receiving tofacitinib (combined doses) versus TNFi were 0.54 versus 0.28 (LATAM) and 1.14 versus 0.92 (non-LATAM) for major adverse cardiovascular events; 0.58 versus 0.27 (LATAM) and 1.33 versus 0.95 (non-LATAM) for malignancies excluding nonmelanoma skin cancer; and 0.69 versus 0.35 (LATAM) and 0.63 versus 0.33 (non-LATAM) for all-cause death. IRs for nonmelanoma skin cancer and venous thromboembolism were also numerically higher with tofacitinib versus TNFi and in the non-LATAM cohort versus LATAM. Efficacy was similar across treatment groups within each cohort. CONCLUSIONS: Adverse events of special interest were generally less frequent in LATAM versus non-LATAM patients, reflecting differences in baseline characteristics, and higher with tofacitinib versus TNFi in both cohorts, consistent with the overall findings of ORAL Surveillance. Our findings emphasize the importance of assessing individual risk factors to guide benefit/risk assessment and treatment decisions. CLINICAL TRIAL REGISTRATION NUMBER: NCT02092467.

Factors Associated With Mortality in Patients With Immune-Mediated Rheumatic Diseases and COVID-19 From Latin America: Data From Argentina, Mexico, and Brazil.

OBJECTIVE: To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population. METHODS: Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded. RESULTS: A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6-12.4), male sex (OR, 1.5; 95% CI, 1.1-2.1), living in Mexico (OR, 3.0; 95% CI, 2.0-4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0-2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3-2.4), and other diseases (OR, 2.6; 95% CI, 1.6-4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5-7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4-2.5) or rituximab (OR, 4.2; 95% CI, 2.7-6.6) were associated with mortality. CONCLUSIONS: Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results.

Acute and Chronic Effects of Strength Training on Plasma Levels of Adipokines in Man.

Adipose tissue is specialized cells that produce and release adipokines. Exercise may modulate adipokine production in adipocytes. The aim of this longitudinal study was to evaluate the acute and chronic effects of strength training (ST) on plasma levels of adiponectin, leptin, and resistin. Twelve untrained young male participants (23.42±2.67 years) were selected. The training protocol consisted of 3 exercises, with 3 sets of 65% of 1RM (one-repetition maximum) with pause of 90 s between sets with duration of 5 s/repetition (2 s conc/3 s ecc), 3 times a week for 10 weeks. Blood was collected at four time points: before and after the first ST session and before and after the last ST session. The comparisons between adipokine levels before and after the same training session showed acute changes, while the comparisons between levels before or after the first session versus before or after the last session revealed chronic alterations. ST increased adiponectin levels after the first exercise session in comparison to levels before this session [50 952 (46 568-51 894) pg/mL vs. 52 981 (49 901-54 467) pg/mL, p=0.019]. Similar differences were observed for resistin levels, which were higher after the last session compared to before [4 214.4 (±829) pg/mL vs. pre-S30 2 251.3 (±462.2) pg/mL, p=0.0008] and in the comparison between after the last and after the first ST sessions [4 214.4 (±829.0) pg/mL vs. 1 563.7 (±284.8) pg/mL, p=0.004]. Leptin levels acutely changed in the last training session. ST produced acute and chronic changes in plasma adipokines.

Participating as a research team during the COVID-19 pandemic benefits mental health of undergraduate medical students in Brazil.

During the COVID-19 pandemic, undergraduate medical students (UMS) exposed to isolation, social distancing and complete or partial face-to-face educational activities interruption may present increased stress, depression and anxiety. This study was undertaken to evaluate if, during isolation, UMS involved in online group activities as investigators of a research project (volunteer group) would present better mental health than their colleagues, not involved in that research (control group). A Web-based survey, via the Google Forms platform, including details on demographic data, life habits, previous health conditions, worries with the COVID-19 pandemic, sleep pattern modifications and depression, anxiety and mental stress, using the DASS-21 (Depression, Anxiety and Stress Scale) was implemented from 20 July to 31 August 2020. Statistical analysis was performed using the SPSS version 20.0. A p-value <0.05 was significant. A total of 684 UMS were included, 228 as a volunteer group and 456 as a control group. Mean age was 23.15 (3.16) years. The groups were paired for age, gender, ethnicity, life habits and previous health conditions. Older age, male gender, participation in the research project, unchanged sleep pattern during the pandemic, lack of fear from getting the COVID-19 and lack of previous health conditions were associated with lower DASS21 scores (better mental health). Participating as investigators of a research project foreseeing frequent interaction with patients, colleagues and professors (other investigators) lead to better mental health during the COVID-19 quarantine in Brazil.

How Did Patients Living With Immune-Mediated Rheumatic Diseases Face the Beginning of the COVID-19 Pandemic in Brazil? Results of the COnVIDa Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has brought additional burden to patients living with immune-mediated rheumatic diseases (IMRDs), especially at the beginning of 2020, for which information for this population is lacking. METHODS: COnVIDa is a cross-sectional study on patients with IMRD from all regions of Brazil who were invited to answer a specific and customized Web questionnaire about how they were facing the COVID-19 pandemic, especially focusing on health care access, use of medications, and patient-reported outcomes related to IMRD activity. The questionnaire was applied from June 1 to 30, 2020. RESULTS: In total, 1722 of 2576 patients who answered the Web questionnaire were included in the final analysis. Participants were most frequently women, 56% were between 31 and 50 years old, and most (55%) has private health insurance. The most commonly reported IMRD was rheumatoid arthritis (39%), followed by systemic lupus erythematosus (28%). During the study period, 30.7% did not have access to rheumatology consultations, and 17.6% stopped chronic medications. Telemedicine was reported in 44.8% of patients. CONCLUSION: COnVIDa demonstrated a negative impact on health care access and treatment maintenance of patients living with IMRD during the COVID-19 pandemic. However, it also presented an uptake of telemedicine strategies. Data presented in this study may assist future coping policies.

Skeletal mass indices are inversely associated with metabolically unhealthy phenotype in overweight/obese and normal-weight men: a population-based cross-sectional study.

Muscle mass may play an important role in the metabolic profile of individuals with or without excess weight. Metabolic phenotypes classify individuals as healthy or unhealthy based on certain metabolic conditions. We investigated the association between skeletal mass indices (SMI) and the metabolically unhealthy phenotype in normal-weight and overweight/obese adults. A total of 660 adults aged 20 to 59 years were assessed by a population-based cross-sectional study. Muscle mass of the limbs or appendicular lean mass (ALM) adjusted for weight (SMIweight) and BMI (SMIBMI) was used to evaluate SMI. Logistic regression was employed to estimate the association between SMIweight, SMIBMI and metabolic phenotypes of normal-weight and overweight/obese individuals. Metabolically unhealthy individuals were older in both sexes. Metabolically unhealthy men had lower SMI values and higher fat percentage than metabolically healthy men. SMIweight was inversely associated with the metabolically unhealthy phenotype, both in normal-weight men (OR 0·49, 95 % CI 0·24, 0·99, P = 0·04) and in overweight/obese men (OR 0·32, 95 % CI 0·16, 0·64, P = 0·001). SMIBMI was inversely associated with the metabolically unhealthy phenotype in overweight/obese men (OR 0·36, 95 % CI 0·18, 0·72, P = 0·004), but not in normal-weight men (OR 0·70, 95 % CI 0·34, 1·43, P = 0·33). Among women, SMI showed no significant association with the phenotypes. In conclusion, the SMI are inversely associated with the metabolically unhealthy phenotype in men, especially among overweight/obese men.

Association between Skeletal Mass Indices and Metabolic Syndrome in Brazilian Adults.

INTRODUCTION: Skeletal muscle is the primary site of glucose uptake and its reduction would increase insulin resistance, which is a determinant factor for diseases such as type 2 diabetes mellitus, hypertension, and metabolic syndrome. However, the role of low skeletal muscle mass as a risk factor for metabolic syndrome and its association with cardiometabolic risk is still uncertain. We aimed to investigate the association between muscle mass (determined by different skeletal mass indices) and metabolic syndrome in Brazilian adults. METHODOLOGY: We conducted a cross-sectional population-based study with 689 adults of both sexes aged between 20 and 59 years. Data were collected through questionnaires and assessment of body composition through dual-energy X-ray absorptiometry and anthropometric, clinical, and biochemical measurements. RESULTS: Older individuals, obese and those with metabolic syndrome predominated in the highest tertile of skeletal mass index adjusted by height (SMIheight), whereas using skeletal mass index adjusted by weight (SMIweight) and skeletal mass index adjusted by body mass index (SMIBMI) these individuals were the majority in the lowest tertile of these indices. In men and women, the adjusted logistic regression model revealed that the highest tertile of SMIweight (odds ratio [OR]: 0.06; 95% confidence interval [CI]: 0.02-0.21 and OR: 0.27, 95% CI: 0.10-0.74) and SMIBMI (OR: 0.14, 95% CI: 0.05-0.37 and OR: 0.34, 95% CI: 0.12-0.94) were negatively associated with metabolic syndrome. On the other hand, the highest tertile of SMIheight was positively associated with metabolic syndrome in both sexes (OR: 4.17, 95% CI: 1.80-9.66 and OR: 6.15, 95% CI: 2.31-16.37, respectively in men and women). CONCLUSION: In adults, the muscle mass assessed from the skeletal mass index adjusted for body weight and body mass index is inversely associated with metabolic syndrome in both sexes.

Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score in Brazilian Portuguese for Adults With Rheumatoid Arthritis.

INTRODUCTION: The Methotrexate Intolerance Severity Score (MISS) questionnaire is used to identify intolerance to methotrexate (MTX), but it is not available in the Brazilian Portuguese language. OBJECTIVE: The aim of this study was to adapt and validate the MISS in Brazilian Portuguese. METHODS: The Brazilian Portuguese version of the MISS was developed following the Guidelines for the Process of Cross-cultural Adaptation of Self-report Measures. The new version was tested in 120 patients with rheumatoid arthritis. For the reliability assessment, the Cronbach α coefficient was used. The receiver operating characteristic curve was constructed with the objective of finding the best cutoff point for MTX intolerance and weighing the sensitivity and specificity. The concordance among the results was analyzed using the κ coefficient and factorial analysis with varimax rotation. RESULTS: This methodological study developed and applied a culturally acceptable Brazilian Portuguese version of the MISS. The MISS questionnaire presented internal consistency classified as "very good" because Cronbach α is equal to 0.83 (95% confidence interval, 0.79-0.87). The suitability of the data for factorial analysis was demonstrated using the Kaiser-Meyer-Olkin sample adequacy test (KMO = 0.723) and Bartlett sphericity test (χ2 = 499.98, p < 0.001). It was observed that a factorial analysis with 3 factors is preferred; the receiver operating characteristic curve of the MISS score was considered the cutoff point at 6 points (sensitivity 100% and specificity 89.4%). CONCLUSIONS: The Brazilian Portuguese version of the MISS is valid and reliable for the detection of MTX intolerance in clinical practice.

Renin-angiotensin system molecules are associated with subclinical atherosclerosis and disease activity in rheumatoid arthritis.

OBJECTIVES: To compare serum levels of RAS components in women with RA versus healthy females and to investigate the association between these molecules and subclinical atherosclerosis. METHODS: A cross-sectional study involving female RA patients without ischemic CVD. Disease activity was assessed using the DAS28 and the CDAI. IMT of the common carotid artery was evaluated by ultrasonography. Serum levels of Ang II, Ang-(1-7), ACE and ACE2 were determined by enzyme immunoassay. RESULTS: Fifty women with RA, mean 48.2 (7.3) years, were compared to 30 healthy women, paired by age. RA patients had higher plasma levels of Ang II (p < .01), Ang-(1-7) (p < .01), and ACE (p < .01) than controls. The ratios of ACE to ACE2 were higher in RA patients, whereas Ang II/Ang-(1-7) ratios were lower in RA patients. The presence of hypertension and the treatment with ACE inhibitors did not significantly modify serum levels of Ang II, Ang-(1-7), ACE and ACE2 in patients with RA. Seven RA patients had altered IMT, and eight patients exhibited atherosclerotic plaque. There was a negative correlation between ACE2 levels and IMT (p = .041). IMT positively correlated with age (p = .022), disease duration (p = .012) and overall Framingham risk score (p = .008). Ang II concentrations positively correlated with DAS28 (p = .034) and CDAI (p = .040). CONCLUSION: Patients with RA had an activation of the RAS, suggesting an association with disease activity and cardiovascular risk. Rheumatological key messages Imbalance of both RAS axes may be associated with cardiovascular risk and disease activity in rheumatoid arthritis. Ultrasonography of the carotid arteries can identify early, subclinical atherosclerotic disease in rheumatoid arthritis patients. Angiotensin-converting enzyme inhibition or angiotensin 1 receptor blockade may be beneficial for rheumatoid arthritis patients.

Leptin as an obesity marker in rheumatoid arthritis.

The determination of excess of body fat mass provides a more suitable determinant of obesity in rheumatoid arthritis patients; however, body mass index (BMI) may not be accurate for the quantification of adiposity. To identify a marker of excess adiposity in women with rheumatoid arthritis (RA) using different methods for fat mass evaluation. A cross-sectional study was conducted in adult female patients with RA. Disease activity was assessed by DAS28-ESR, and obesity was determined by waist circumference (WC), BMI and dual-energy X-ray absorptiometry (DXA). The Human Bone Metabolism kit (Merck Millipore, Darmstadt, Alemanha) was used to determine the plasma levels of leptin, TNF-α, IL-6, and IL-1ß by quantification of serum proteins by technical microspheres (LUMINEX, TX, USA). Adiponectin was measured by enzyme-linked immunosorbent assay sandwich kit (R&D Systems, Minneapolis, MN, USA). Eighty-nine female patients, median age of 55.4 (± 11.6) years, and median disease duration of 16.4 (± 14.9) years were included. The frequency of obesity was 33.7% according to BMI, 89.9% with WC, and 56.1% with DXA. The median serum leptin concentration was the only marker that correlated with body fat percentage according to the three methods. This correlation was positive and not influenced by DAS28, C-reactive protein, erythrocyte sedimentation rate, or inflammatory cytokines levels (IL-6, TNF-α, IL-1ß). Analysis of ROC curves determined the cut-off point of 10.3 ng/mL of leptin as an obesity marker, with a sensitivity of 96.43% and a specificity of 23.81%. Serum leptin correlates positively with fat mass and is potentially useful in excess fat mass determination in clinical practice.

Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis.

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

Undifferentiated spondyloarthritis in a heterogeneous Brazilian population: an eight-year follow-up study.

The aim of the present study was to describe the outcomes of Brazilian patients with undifferentiated spondyloarthritis during an eight-year follow-up period. Patients fulfilling the European Spondyloarthritis (SpA) Study Group Classification Criteria were enrolled. Forty patients were seen at baseline, and 36 participated in the follow-up study. Twenty-three (58%) were female, and there were 24 (60%) African Brazilians enrolled. HLA-B27 was positive in 18 (45%) patients. At disease onset, the first presenting symptoms were pure peripheral manifestations in 26 (72.2%) patients. After the study period, mixed disease (axial + peripheral) predominated occurring in 25 (69.4%) patients. The Assessment of SpA International society (ASAS) classification criteria for axial SpA were fulfilled by 77% of patients, and the ASAS criteria for peripheral SpA were fulfilled by 59% of patients. After 2.5 years, 6 (16.7%) of the 36 patients fulfilled the modified New York Criteria for ankylosing spondylitis and 1 (2.7%) progressed to psoriatic arthritis. A total of 10 (27.8%) patients progressed to definite SpA during the eight-year study period. Buttock pain (p = 0.006, OR 10.55; 95% CI 2.00-65.90) and low-grade radiographic sacroiliitis (p = 0.025, OR = 11.50; 95% CI 1.33-83.39) at baseline were associated with definite SpA. Thus, in this Brazilian cohort, which had a predominance of female African-Brazilian patients, prevalent peripheral onset symptoms were followed by a high frequency of axial manifestations during the follow-up period. Evidence of clinical or radiological sacroiliitis was associated with progression to definite SpA.

Treatment of psoriatic arthritis with anti-TNF agents: a systematic review and meta-analysis of efficacy, effectiveness and safety.

We did a systematic review and meta-analysis on the efficacy and safety of the anti-TNF drugs adalimumab, etanercept, golimumab and infliximab used in psoriatic arthritis (PsA) adult treatment. Additionally, we present results of anti-TNF use in real life settings. We searched Embase, Medline, Cochrane Central and LILACS, from inception to 11/08/2013, for studies comparing anti-TNFs with each other or with controls. We included nine randomized controlled trials and six observational studies. ACR20, ACR50, PsARC and PASI75 responses were achieved by more users of anti-TNF than control after up to 24 weeks of treatment. More participants who used etanercept and infliximab achieved ACR70. After all patients originally randomized to anti-TNF or placebo had used anti-TNF for at least 24 weeks, we observed difference only with regard to ACR70 response. Radiographic end points were achieved by more patients in anti-TNF group, and they seem to be time dependent-the longer patients use the drug the better the results. Etanercept and infliximab had worse results on application site reactions, but in general anti-TNF drugs in the regimens studied were as safe as control/placebo. There seems to be no difference in efficacy and effectiveness among anti-TNFs, but superiority head-to-head studies are still needed. Meanwhile, other factors should be taken into account in the choice of medication, such as costs and patient convenience.

Challenges in implementing treat-to-target in rheumatoid arthritis: a perspective from Brazilian rheumatologists.

BACKGROUND: Patient management in rheumatoid arthritis (RA) has evolved to a "treat-to-target" (T2T) approach, which entails intensive treatment and regular follow-up with the goal of achieving low levels of disease activity or clinical remission. Even though a T2T approach is endorsed by professional organizations and yields superior outcomes, its implementation remains incomplete. EVEREST (EleVatE care in RhEumatoid arthritiS with Treat-to-target) is a quality-improvement initiative designed to improve the widespread implementation of a personalized T2T strategy and enable patients with RA to reach their full potential for remission. We describe the Brazilian results from the Global T2T Survey, first part of the EVEREST program. METHODS: Between June and September 2022, we conducted an online survey targeting rheumatologists in Brazil. Our objective was to evaluate the barriers and knowledge gaps hindering the effective implementation of T2T strategies. To achieve this, we employed a set of multiple-choice questions specifically crafted to elicit responses categorized in a structured order. RESULTS: 166 rheumatologists participated in the survey, 51% of them with more than 21 years of experience in rheumatology. Regarding the perceived challenges in the management of RA in clinical practice, the highest percentage of agreement/strong agreement among the participants was related to the contradictory results of disease activity measures (60%). In terms of the main barriers to assess the disease activity in clinical practice, the lack of adherence to treatment and contradictory assessments between patient-reported outcomes and composite measures were indicated by 75% and 59% of the participants, respectively, as a moderate/serious barrier. The most frequently knowledge and skill gaps related to the management of RA pointed out by the participants were on the difficulty to assess patients' health literacy (54% stated to have no more than intermediate knowledge on standardized methods to assess it and 43% no more than intermediate skills on determining the level of health literacy of the patients). In general, the use of tools to support the management of RA patients in clinical practice was indicated to be unusual by the participants. Self-reflection questionnaires, patient education materials and treatment consideration checklists were pointed out as the least frequently used tools (85%, 64% and 62% of the participants stated to use them never, rarely, or only sometimes, respectively). CONCLUSIONS: Our findings indicate a greater need for design, selection, and uptake of practical strategies to further improve communication between healthcare providers and patients with RA, as well as for promoting well-informed, collaborative decision-making in their care.

Agreement and diagnostic differences among three definitions of sarcopenia in patients with chronic hepatitis C.

BACKGROUND: There is neither a gold standard definition nor a universal consensus to diagnose sarcopenia in patients with chronic hepatitis C. Thus, we aimed to compare the prevalence of sarcopenia and the agreement and discrepancies between European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, and Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project (FNIH) definitions in chronic hepatitis C. METHODS: Dual-energy x-ray absorptiometry was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for squared height (ALM/ht2) or for body mass index (ALMBMI). Muscle function was evaluated by handgrip strength. Subjective Global Assessment was used to assess the nutrition status. RESULTS: This cross-sectional study included 103 outpatients (mean age, 50.6 ± 11.3 years; 33.0% with compensated cirrhosis). Sarcopenia prevalence was 8.7%, 9.7%, and 9.7%, according to EWGSOP1, EWGSOP2, and FNIH definitions, respectively. There was neither a sex- nor a liver disease severity-specific difference in the prevalence of sarcopenia between the criteria applied. Sixteen (15.5%) patients fulfilled at least one of these criteria, and 3 out of 16 (18.8%) simultaneously had sarcopenia by consensus of the three criteria. Sarcopenic obesity was identified in 9 out of 16 (56.3%) patients, and 6 out of 9 (66.7%) of these only met FNIH consensus. CONCLUSIONS: In patients without cirrhosis or with compensated cirrhosis, and with chronic hepatitis C, the agreement between EWGSOP1 and EWGSOP2 classifications was substantial for sarcopenia diagnosis. Concerning EWGSOP and FNIH criteria, a fair agreement and limited overlap were found in these patients.

Socioeconomic factors and COVID-19 mortality in immune-mediated rheumatic diseases patients: regional analysis from Argentina, Mexico and Brazil.

BACKGROUND: SARS-CoV-2 infection has become a major international issue, not only from a medical point of view, but also social, economic and political. Most of the available information comes from the United States, Europe, and China, where the population and the socioeconomic status are very different from Latin American countries. This study evaluates the effect of regional socioeconomic characteristics on mortality due SARS-CoV-2 infection in patients with immune-mediated rheumatic diseases (IMRD) from Argentina, Mexico and Brazil. METHODS: Data from three national registries, SAR-COVID (Argentina), CMR-COVID (Mexico) and ReumaCoV-Brasil (Brazil), were combined. Adult IMRD patients with SARS-CoV-2 infection were recruited. National data for each province/state, including population density, number of physicians per inhabitant, income, unemployment, GINI index, Municipal Human Development Index (MHDI), stringency index, vaccination rate and most frequent viral strains per period were assessed as risk factors for mortality due to COVID-19. RESULTS: A total of 4744 patients were included, 2534 (53.4%) from SAR-COVID, 1166 (24.6%) from CMRCOVID and 1044 (22.0%) from ReumaCoV-Brasil. Mortality due to COVID-19 was 5.4%. In the multivariable analysis, higher number of physicians per 1000 inhabitants and being infected during the vaccination period of each country were associated with lower mortality. After adjustment for socioeconomic factors, there was no association with country of residence and mortality. CONCLUSION: These findings corroborate the complex interplay between socioeconomic factors, rheumatic disease activity, and regional disparities as determinants of death due to COVID-19 in Argentina, Brazil and Mexico. Thus, this research provides valuable insights for guiding public health policies and clinical practice in the ongoing fight against the COVID-19 pandemic.

Predictors of Hospitalization in Breakthrough COVID-19 among Fully Vaccinated Individuals with Immune-Mediated Rheumatic Diseases: Data from SAFER-Study.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9-18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02-8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15-0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients.

Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis.

Biological agents directed against tumor necrosis factor (TNF) represent therapeutic options for patients with ankylosing spondylitis with high disease activity despite use of non-steroidal anti-inflammatory drugs. To evaluate the efficacy and safety of the anti-TNF agents infliximab, etanercept, adalimumab, golimumab, and certolizumab for the treatment of ankylosing spondylitis, we performed a systematic review of randomized clinical trials on adult patients with ankylosing spondylitis using articles culled from the EMBASE, MEDLINE, Cochrane Controlled Trials Register and LILACS databases (September/2012), manual literature search, and the gray literature. Study selections and data collection were performed by two independent reviewers, with disagreements solved by a third reviewer. The following outcomes were evaluated: ASAS 20 response, disease activity, physical function, vertebral mobility, adverse events, and withdraws. The meta-analysis was performed using the Review Manager(®) 5.1 software by applying the random effects model. Eighteen studies were included in this review. No study of certolizumab was included. Patients treated with anti-TNF agents were more likely to display an ASAS 20 response after 12/14 weeks (RR 2.21; 95 % CI 1.91; 2.56) and 24 weeks (RR 2.68; 95 % CI 2.06; 3.48) compared with controls, which was also true for several other efficacy outcomes. Meta-analysis of safety outcomes and withdraws did not indicate statistically significant differences between treatment and control groups after 12 or 30 weeks. Adalimumab, infliximab, etanercept, and golimumab can effectively reduce the signs and symptoms of the axial component of ankylosing spondylitis. Safety outcomes deserve further study, especially with respect to long-term follow-ups.

Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis.

BACKGROUND: Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). METHODS: FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1ß. RESULTS: RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1ß by CIA-FLSs than by RA-FLSs. CONCLUSION: This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program.

INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW). METHODS: Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed. RESULTS: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations. CONCLUSION: Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed. TRIAL REGISTRATION NUMBERS: SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343.