Publications by authors named "Bernardo Pons-Estel"

101 Publications

A longitudinal multiethnic study of biomarkers in systemic lupus erythematosus: Launching the GLADEL 2.0 Study Group.

Lupus 2021 Jan 28:961203320988586. Epub 2021 Jan 28.

Sección de Reumatología, Departamento de Medicina Interna/Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Universidad de Antioquía, Medellín, Colombia.

After more than 20 years of sustained work, the Latin American Group for the Study of Lupus (GLADEL) has made a significant number of contributions to the field of lupus, not only in the differential role that race/ethnicity plays in its course and outcome but also in several other studies including the beneficial effects of using antimalarials in lupus patients and the development of consensus guidelines for the treatment of lupus in our region. A new generation of "Lupus Investigators" in more than 40 centers throughout Latin America has been constituted in order to continue the legacy of the investigators of the original cohort and to launch a novel study of serum and urinary biomarkers in patients with systemic lupus erythematosus. So far, we have recruited 807 patients and 631 controls from 42 Latin-American centers including 339 patients with SLE without renal involvement, 202 patients with SLE with prevalent but inactive renal disease, 176 patients with prevalent and active renal disease and 90 patients with incident lupus nephritis. The different methodological aspects of the GLADEL 2.0 cohort are discussed in this manuscript, including the challenges and difficulties of conducting such an ambitious project.
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http://dx.doi.org/10.1177/0961203320988586DOI Listing
January 2021

Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL).

RMD Open 2020 12;6(3)

Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, Mexico.

Aim: A decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.

Methods: We included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.

Results: Five hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.

Conclusions: Early response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.
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http://dx.doi.org/10.1136/rmdopen-2020-001299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859505PMC
December 2020

Access to healthcare system of indigenous communities with musculoskeletal disorders and rheumatic disease in Chaco, Argentina: a qualitative study.

Clin Rheumatol 2020 Nov 24. Epub 2020 Nov 24.

Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Bv. Oroño 1024, Rosario, Santa Fe, Argentina.

Introduction/objectives: The objective of this study is to describe the local healthcare system from the perspective of the health professionals, community health workers, and local representatives of the qom community living in the province of Chaco, Argentina.

Methods: A qualitative study, with an ethnographic approach, was carried out using two techniques: non-participant observations and semi-structured interviews. A guide for the interviews was designed and developed by a multidisciplinary group of GLADERPO researchers. The main aspects included were the following: reference into the local healthcare system and accessibility to the system. Andersen's base conceptual model of health service utilization was applied for the analysis and for structuring the results.

Results: A total of 21 people were interviewed, twelve women and nine men with an age ranging between 25 and 60 years old. The main findings were different barriers (communication and cultural) between the community and the healthcare system; "navigation" within the health system carried out by the qom community; and migration and bureaucratization of the health system.

Conclusions: These findings should be incorporated into educational strategies to improve access to healthcare system and adherence to medical treatment, establishing an interaction between the different levels of the local care system and providing community health workers with an appropriate training with the support of the community representatives. Key Points • The different barriers between the community and the healthcare system were described. • The "navigation" within the health system carried out by the qom community and the migration were relevant points. • The bureaucratization of the health system and the need to design and implement educational strategies in the future were highlighted.
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http://dx.doi.org/10.1007/s10067-020-05513-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685194PMC
November 2020

Prevalence of Sarcopenia and Whole-Body Composition in Rheumatoid Arthritis.

J Clin Rheumatol 2020 Sep 4. Epub 2020 Sep 4.

Bone Biology Laboratory, School of Medicine, Rosario National University, Rosario.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformity and disability, as well as muscle involvement. Sarcopenia is characterized by a progressive age-related loss of muscle mass and strength.

Aim: The aim of this study was to evaluate the prevalence of sarcopenia and possible contributing factors associated with sarcopenia in RA patients.

Patients And Methods: Adult RA patients (n = 105) of both sexes and 100 subjects as control group (CG) matched by age, sex, and body mass index were included in this cross-sectional study. Whole-body composition was measured by dual-energy x-ray absorptiometry. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass [ASM] index by dual-energy x-ray absorptiometry). The association between sarcopenia and associated factors was evaluated using logistic regression analyses.

Results: Significantly lower percentage of lean mass and ASM were found in the whole RA group compared with controls. However, lower lean parameters (total lean mass, percentage of lean mass, and ASM) were observed only in female subjects. The ASM index was significantly lower in female subjects with RA (RA 31.0% vs CG 11.9%) without differences in male subjects. On the other hand, fat mass and most adipose indices were significantly higher in both female and male subjects with RA. Female RA patients had higher prevalence of sarcopenia and sarcopenic obesity. Through univariate logistic regression analysis, the time of corticoids use, cumulative corticosteroid dose, previous fragility fractures, total lean mass, and ASM were associated with sarcopenia.

Conclusions: Higher prevalence of sarcopenia and sarcopenic obesity were found in female RA patients. Sarcopenia was found in younger female subjects with RA compared with healthy control subjects. Sarcopenia was associated with previous fragility fractures in female patients with RA.
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http://dx.doi.org/10.1097/RHU.0000000000001549DOI Listing
September 2020

Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort.

Lupus 2020 Aug 30;29(9):1140-1145. Epub 2020 Jun 30.

Centro Médico ABC, Ciudad de México, Mexico.

Objectives: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE).

Methods: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality.

Results: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%;  = 0.04) and musculoskeletal (6.1% vs. 1.9%;  = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81).

Conclusion: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.
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http://dx.doi.org/10.1177/0961203320935184DOI Listing
August 2020

«Living with Rheumatoid Arthritis» in an Indigenous Qom Population in Argentina. A Qualitative Study.

Reumatol Clin 2020 Jun 26. Epub 2020 Jun 26.

Hospital General de México Dr. Eduardo Liceaga, Ciudad de México, México.

Introduction: Rheumatoid arthritis (RA) is a chronic disease which impacts patients' quality of life. The prevalence of RA in the qom population was 2.4% and represented an aggressive and disabling disease. The study goal was to describe the experience of the indigenous qom community individual suffering from RA, along with their experience with the local health care system in the city of Rosario, Santa Fe, Argentina.

Methods: Qualitative Study using techniques of participant observation and semi-structured interviews; following a guideline developed by a multidisciplinary research group comprising anthropologists, rheumatologists, nurses, and psychologists. A triangulation strategy was implemented for the analysis.

Results: A total of 33 interviews were conducted in 29 individuals with RA. The results showed a «normalization» of their symptoms and of their limitations in performing daily tasks. The individual relationships with the local health care system was complex and limited in several aspects (e.g. access to health care, continuity of treatment, complexity of medical care pathway and lack of cultural competence).

Conclusions: RA is a disease that has a negative impact on the daily lives of the qom people living in Rosario. Improving the relationship between this population and the local health care system as well as the implementation of multidisciplinary work should be priorities.
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http://dx.doi.org/10.1016/j.reuma.2020.04.016DOI Listing
June 2020

Prevalence of musculoskeletal disorders and rheumatic diseases in an Argentinean indigenous Wichi community.

Clin Rheumatol 2021 Jan 5;40(1):75-83. Epub 2020 Jun 5.

Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Santa Fe, Argentina.

Objective: To estimate the prevalence of musculoskeletal disorders (MSK) and rheumatic diseases in an indigenous Wichi population in Argentina.

Methods: This is a cross-sectional, community-based study using the Community-Oriented Program for the Control of Rheumatic Diseases (COPCORD) methodology in ≥ 18-year-old subjects. Validated surveys were conducted by trained interviewers. Subjects with MSK pain (positive cases) were evaluated by internists and rheumatologists for diagnosis and treatment.

Results: A total of 648 interviews were performed (90.4% of the census population). Mean age was 37.5 years (SD 14.8), and 379 (58.5%) were female. The mean years of education was 7.0 (SD 3.7); 552 subjects (85.2%) were covered by the public health care system. A total of 216 (33.3%) subjects had MSK pain in the last 7 days. Rheumatic disease prevalence was as follows: mechanical back pain (19.0%), rheumatic regional pain syndrome (5.2%), osteoarthritis (3.2%), rheumatoid arthritis (RA) (3.2%), inflammatory back pain (1.2%), undifferentiated arthritis (0.3%), Sjögren syndrome (0.15%), and fibromyalgia (0.15%). RA patients included 19 (90.5%) women and 9 (42.9%) with RA family history. One hundred percent were seropositive and 66.7% showed radiologic erosions. The mean of Disease Activity Score [DAS-28 (ESR)] at the time of diagnosis was 5.1 (SD 1.5) and the Health Assessment Questionnaire Disability Index (HAQ-DI) was 0.8 (SD 0.4).

Conclusion: RA prevalence was 3.2%, one of the highest reported using the COPCORD methodology in indigenous and non-indigenous peoples in Latin America, with a high percentage of family cases. Pain and functional capacity were the variables allowing patients' early referral to a specialist. Key Points • The RA prevalence was 3.2%, one of the highest reported using COPCORD methodology in indigenous and non-indigenous peoples in Latin America. • The patients with RA had high percentage of familiar history of RA. • The pain and functional capacity were the variables associated with a diagnosis of any rheumatic disease and should be considered for early referral. • The mean of the delay in the diagnosis was 5.8 years. In this community, the lack of the "migration health" phenomenon may be a social determinant that negatively impacts their health.
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http://dx.doi.org/10.1007/s10067-020-05130-3DOI Listing
January 2021

Syndemic and syndemogenesis of low back pain in Latin-American population: a network and cluster analysis.

Clin Rheumatol 2020 Sep 30;39(9):2715-2726. Epub 2020 Mar 30.

Rheumatology Unit. Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico.

Introduction: Although low back pain (LBP) is a high-impact health condition, its burden has not been examined from the syndemic perspective.

Objective: To compare and assess clinical, socioeconomic, and geographic factors associated with LBP prevalence in low-income and upper-middle-income countries using syndemic and syndemogenesis frameworks based on network and cluster analyses.

Methods: Analyses were performed by adopting network and cluster design, whereby interrelations among the individual and social variables and their combinations were established. The required data was sourced from the databases pertaining to the six Latin-American countries.

Results: Database searches yielded a sample of 55,724 individuals (mean age 43.38 years, SD = 17.93), 24.12% of whom were indigenous, and 60.61% were women. The diagnosed with LBP comprised 6.59% of the total population. Network analysis showed higher relationship individuals' variables such as comorbidities, unhealthy habits, low educational level, living in rural areas, and indigenous status were found to be significantly associated with LBP. Cluster analysis showed significant association between LBP prevalence and social variables (e.g. Gender inequality Index, Human Development Index, Income Inequality).

Conclusions: LBP is a highly prevalent condition in Latin-American populations with a high impact on the quality of life of young adults. It is particularly debilitating for women, indigenous individuals, and those with low educational level, and is further exacerbated by the presence of comorbidities, especially those in the mental health domain. Thus, the study findings demonstrate that syndemic and syndemogenesis have the potential to widen the health inequities stemming from LBP in vulnerable populations. Key points • Syndemic and syndemogenesis evidence health disparities in Latin-American populations, documenting the complexity of suffering from a disease such as low back pain that is associated with comorbidities, unhealthy habits, and the social and regional context where they live. • The use of network and cluster analyses are useful tools for documenting the complexity and the multifaceted impact in health in large populations as well as the differences between countries. • The variability and impact of socioeconomic indicators (e.g., Gini index) related to low back pain and comorbidities could be felt through the use of cluster analysis, which generates evidence of regional inequality in Latin America. • Populations can be studied from different models (network and cluster analysis) and grouping, presenting new interpretations beyond geographical groupings, such as syndemic and inequity in health.
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http://dx.doi.org/10.1007/s10067-020-05047-xDOI Listing
September 2020

Applying the 2019 EULAR/ACR lupus criteria to patients from an established cohort: a Latin American perspective.

RMD Open 2020 01;6(1)

Department of Medicine, Division of Clinical Immunology and Rheumatology, School of Medicine, The University of Alabama, Birmingham, Alabama, USA.

Objective: To evaluate the performance of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) criteria in terms of earlier patients' classification in comparison to the 1982/1997 ACR or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria.

Materials And Methods: Patients from a Latin America, multiethnic, multicentre cohort, where SLE was defined using the physicians' diagnosis, were included. To calculate the sensitivity of the 2019 EULAR/ACR criteria, the 1982/1997 ACR criteria were considered the gold standard. Additionally, comparison of the 1982/1997 ACR criteria and the 2012 SLICC criteria with the 2019 EULAR/ACR criteria was performed.

Results: The sensitivity of the 2019 EULAR/ACR criteria when compared with the 1982/1997 ACR criteria as the gold standard was 91.3%. This new set of criteria allowed an earlier SLE patient classification in 7.4% (mean 0.67 years) and 0.6% (mean 1.47 years) than the 1982/1997 ACR and the 2012 SLICC criteria, respectively. Patients accruing the 2019 EULAR/ACR earlier than the 1982/1997 ACR criteria were more likely to have high anti-dsDNA titres; those accruing them later were less likely to have mucocutaneous and joint manifestations; this was not observed when comparing them with the 2012 SLICC criteria.

Conclusions: The 2019 EULAR/ACR criteria classified earlier only a small proportion of Latin America patients than with the two other criteria sets in real-life clinical practice scenarios. Further studies in different patient populations are needed before these new criteria are adopted worldwide.
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http://dx.doi.org/10.1136/rmdopen-2019-001097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999682PMC
January 2020

A Critical Analysis of the First Latin American Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus.

J Clin Rheumatol 2019 Dec 31. Epub 2019 Dec 31.

Departamento de Medicina Interna, Grupo Oroño-Centro Regional de Enfermedades Autoinmunes (GO-CREAR), Rosario, Argentina.

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http://dx.doi.org/10.1097/RHU.0000000000001265DOI Listing
December 2019

Differential Treatments Based on Drug-induced Gene Expression Signatures and Longitudinal Systemic Lupus Erythematosus Stratification.

Sci Rep 2019 10 29;9(1):15502. Epub 2019 Oct 29.

Centro de Genómica e Investigaciones Oncológicas Pfizer-Universidad de Granada-Junta de Andalucía (GENYO), Granada, Spain.

Systemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.
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http://dx.doi.org/10.1038/s41598-019-51616-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820741PMC
October 2019

Jaccoud's arthropathy in SLE: findings from a Latin American multiethnic population.

Lupus Sci Med 2019 12;6(1):e000343. Epub 2019 Aug 12.

Department of Internal Medicine, Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Rosario, Argentina.

Objective: To compare the clinical, laboratory and outcome features of SLE patients with and without Jaccoud's arthropathy (JA) from the (GLADEL) cohort.

Methods: 1480 patients with SLE [(34 centres, 9 Latin American countries with a recent diagnosis (≤2 years)] constitute the GLADEL cohort. JA was defined as reducible deformity of the metacarpophalangeal axis, without radiographic erosions at any time. Within this cohort, a nested case-control study was carried out. Control was matched for age, gender and centre in a 1:3 proportion. The variables included were: sociodemographic, clinical and immunological features, disease activity, damage and mortality. Comparisons were performed with Wilcoxon and χ tests for continuous and categorical variables, respectively. ORs and 95% CIs and Kaplan-Meier survival curve were estimated.

Results: Of 1480 patients, 17 (1.1%) JA patients were identified; 16 (94.1%) of them were women, mean age: 31.0 years (SD 12.0). Five (29.4%) patients presented JA at SLE diagnosis and 12 (70.6%) after. The median follow-up time and all disease features were comparable in both groups except for a higher frequency of pneumonitis in the patients with JA [4 (23.5) vs 1 (2.0); p=0.012; (OR: 15.4; 95% CI 1.6 to 149.6)]. The SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage Index and the Kaplan-Meier survival curve were similar in both groups.

Conclusion: JA may tend to appear early in the course of SLE; it seems not to have an impact on disease activity, damage accrual or in survival.
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http://dx.doi.org/10.1136/lupus-2019-000343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703282PMC
August 2019

Clinical predictors of remission and low disease activity in Latin American early rheumatoid arthritis: data from the GLADAR cohort.

Clin Rheumatol 2019 Oct 3;38(10):2737-2746. Epub 2019 Jun 3.

Complejo Hospitalario Metropolitano Dr. Arnulfo Arias Madrid, Caja de Seguro Social de Panamá, Panama City, Panama.

Objectives: To identify baseline predictors of remission and low disease activity (LDA) in early rheumatoid arthritis (RA) from the GLADAR (Grupo Latino Americano De estudio de la Artritis Reumatoide) cohort.

Methods: Patients with 1- and 2-year follow-up visits were included. Remission and LDA were defined by DAS28-ESR (< 2.6 and ≤ 3.2, respectively). Baseline predictors examined were gender, ethnicity, age at diagnosis, socioeconomic status, symptoms' duration, DMARDs, RF, thrombocytosis, anemia, morning stiffness, DAS28-ESR (and its components), HAQ-DI, DMARDs and corticosteroid use, and Sharp-VDH score. Multivariable binary logistic regression models (excluding DAS28-ESR components to avoid over adjustment) were derived using a backward selection method (α-level set at 0.05).

Results: Four hundred ninety-eight patients were included. Remission and LDA/remission were met by 19.3% and 32.5% at the 1-year visit, respectively. For the 280 patients followed for 2 years, these outcomes were met by 24.3% and 38.9%, respectively. Predictors of remission at 1 year were a lower DAS28-ESR (OR 1.17; CI 1.07-1.27; p = 0.001) and HAQ-DI (OR 1.48; CI 1.04-2.10; p = 0.028). At 2 years, only DAS28-ESR (OR 1.40; CI 1.17-1.6; p < 0.001) was a predictor. Predictors of LDA/remission at 1 year were DAS28-ESR (OR 1.42; CI 1.26-1.61; p < 0.001), non-use of corticosteroid (OR 1.74; CI 1.11-2.44; p = 0.008), and male gender (OR 1.77; CI 1.2-2.63; p = 0.036). A lower baseline DAS28-ESR (OR 1.45; CI 1.23-1.70; p < 0.001) was the only predictor of LDA/remission at 2 years.

Conclusions: A lower disease activity consistently predicted remission and LDA/remission at 1 and 2 years of follow-up in early RA patients from the GLADAR cohort. Key Points • In patients with early RA, a lower disease activity at first visit is a strong clinical predictor of achieving remission and LDA subsequently. • Other clinical predictors of remission and LDA to keep in mind in these patients are male gender, non-use of corticosteroids and low disability at baseline. • Not using corticosteroids at first visit is associated with a lower disease activity and predicts LDA/remission at 1 year in these patients.
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http://dx.doi.org/10.1007/s10067-019-04618-xDOI Listing
October 2019

Predictors of Remission and Low Disease Activity State in Systemic Lupus Erythematosus: Data from a Multiethnic, Multinational Latin American Cohort.

J Rheumatol 2019 10 1;46(10):1299-1308. Epub 2019 Mar 1.

From the Department of Rheumatology, Hospital Guillermo Almenara Irigoyen, EsSalud; Universidad Científica del Sur, Lima, Peru; Grupo Latino Americano De Estudio de Lupus (GLADEL), Rosario, Argentina; Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain; Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Grupo Oroño, Sanatorio Parque, Rosario, Santa Fe, Argentina; Servicio de Reumatología, Hospital Clinic, Barcelona, Spain; Sección de Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires, Instituto Universitario, Escuela de Medicina Hospital Italiano and Fundación Dr. Pedro M. Catoggio para el Progreso de la Reumatología, Buenos Aires; Servicio de Reumatología, Hospital Privado, Centro Medico de Córdoba, Córdoba, Argentina; Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo; Disciplina de Reumatologia, Escola Paulista de Medicina/UNIFESP, Hospital São Paulo, Universidade Federal de São Paulo, São Paulo; Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas; Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, Brazil; Clínica Saludcoop 104 Jorge Piñeros Corpas and Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogotá, Colombia; Hospital del Salvador, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Servicio de Reumatología, Centro de Investigaciones Médico Quirúrgicas-CIMEQ, Havana, Cuba; Centro de Investigación Clínica de Morelia SC, Morelia, Michoacán; Reumatología, Centro Médico ABC, Ciudad de México, México; Universidad Nacional Mayor de San Marcos, Lima, Peru; Hospital Central de San Cristóbal, San Cristóbal, Venezuela; Department of Medicine, Division of Clinical Immunology and Rheumatology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Objective: To determine the predictors of remission and low disease activity state (LDAS) in patients with systemic lupus erythematosus (SLE).

Methods: Three disease activity states were defined: Remission = SLE Disease Activity Index (SLEDAI) = 0 and prednisone ≤ 5 mg/day and/or immunosuppressants (maintenance dose); LDAS = SLEDAI ≤ 4, prednisone ≤ 7.5 mg/day and/or immunosuppressants (maintenance dose); and non-optimally controlled state = SLEDAI > 4 and/or prednisone > 7.5 mg/day and/or immunosuppressants (induction dose). Antimalarials were allowed in all groups. Patients with at least 2 SLEDAI reported and not optimally controlled at entry were included in these analyses. Outcomes were remission and LDAS. Multivariable Cox regression models (stepwise selection procedure) were performed for remission and for LDAS.

Results: Of 1480 patients, 902 were non-optimally controlled at entry; among them, 196 patients achieved remission (21.7%) and 314 achieved LDAS (34.8%). Variables predictive of a higher probability of remission were the absence of mucocutaneous manifestations (HR 1.571, 95% CI 1.064-2.320), absence of renal involvement (HR 1.487, 95% CI 1.067-2.073), and absence of hematologic involvement (HR 1.354, 95% CI 1.005-1.825); the use of immunosuppressive drugs before the baseline visit (HR 1.468, 95% CI 1.025-2.105); and a lower SLEDAI score at entry (HR 1.028, 95% CI 1.006-1.051 per 1-unit decrease). These variables were predictive of LDAS: older age at entry, per 5-year increase (HR 1.050, 95% CI 1.004-1.098); absence of mucocutaneous manifestations (HR 1.401, 95% CI 1.016-1.930) and renal involvement (HR 1.344, 95% CI 1.049-1.721); and lower SLEDAI score at entry (HR 1.025, 95% CI 1.009-1.042).

Conclusion: Absence of mucocutaneous, renal, and hematologic involvement, use of immunosuppressive drugs, and lower disease activity early in the course of the disease were predictive of remission in patients with SLE; older age was predictive of LDAS.
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http://dx.doi.org/10.3899/jrheum.180433DOI Listing
October 2019

Evaluation of the Educational Needs in Argentine Patients with Rheumatoid Arthritis Using the SpENAT Questionnaire.

Reumatol Clin 2020 Sep - Oct;16(5 Pt 2):386-390. Epub 2018 Oct 29.

Sanatorio Parque S. A., Rosario, Santa Fe, Argentina.

Background: The SpENAT, a Spanish version of the Educational Needs Assessment Tool, is a self-completed questionnaire that assesses educational needs (ENs) with the purpose of providing tailored and patient-centered information. It consists of 39 questions grouped into the 7 following domains: Pain management, Movement, Feelings, Arthritic process, Treatments, Self-help measures and Support system.

Objectives: The objective of the study was to describe the ENs of rheumatoid arthritis (RA) patients using the SpENAT and to determine the main sources of information consulted by these patients.

Material And Methods: Multicenter, observational, cross-sectional study. We included consecutive patients≥18 years with diagnosis of RA (ACR 87/ACR-EULAR 2010). Sociodemographic data, disease characteristics and clinimetric properties were recorded. All patients completed the SpENAT and were asked about the sources employed to obtain information about their disease.

Statistical Analysis: Population characteristics were described. ENs were determined as percentages of the highest possible score for each domain. Needs for each domain according to sex, years of education, disease duration, use of biologicals and functional capacity were analyzed by means of ANOVA, and bivariate comparisons were made with Student's t-test and the Bonferroni correction. Correlation between domains was determined with the Spearman correlation coefficient. We compared patients' age by source of information with Student's t-test.

Results: We included 496 patients from 20 centers across the country. More ENs were observed in the domains of Movement, Feelings and the Arthritic process. Patients with higher educational level (>7 years) reported more ENs in the Arthritic process and Self-help measure domains. A higher functional impairment (HAQ-A≥0.87) was associated with more ENs in every domain. Patients with high activity showed more ENs than those in remission in the domains of Pain management, Movement, Feelings, Treatments and Support system, as well as those with low activity in Self-help measures and Support system domains. All SpENAT domains showed positive correlations among each other (P<.0001), the most important being Pain management/Movement and Treatments/Arthritic process (r≥0.7). The source of information most frequently consulted was the rheumatologist (93.95%); those who made use of Internet were on average younger (P=.0004).

Conclusion: RA patients were very interested about knowing more about their disease. High functional impairment was associated with more ENs. Patients with high disease activity had higher EN levels in almost every domain. The rheumatologist was the main source of information for the patient with RA.
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http://dx.doi.org/10.1016/j.reuma.2018.09.002DOI Listing
October 2018

Response to: 'Clinical evidence guidelines in systemic lupus erythematosus: revaluation' by Scheinberg.

Ann Rheum Dis 2019 11 23;78(11):e120. Epub 2018 Oct 23.

Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.

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http://dx.doi.org/10.1136/annrheumdis-2018-214385DOI Listing
November 2019

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, )-Pan-American League of Associations of Rheumatology (PANLAR).

Ann Rheum Dis 2018 11 25;77(11):1549-1557. Epub 2018 Jul 25.

Servicio de Reumatología, Hospital Italiano de Córdoba, Córdoba, Argentina.

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.
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http://dx.doi.org/10.1136/annrheumdis-2018-213512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225798PMC
November 2018

Epidemiology and socioeconomic impact of the rheumatic diseases on indigenous people: an invisible syndemic public health problem.

Ann Rheum Dis 2018 10 14;77(10):1397-1404. Epub 2018 Jul 14.

Rheumatology Department, Regional Center for Autoimmune and Rheumatic Diseases (Centro Regional de Enfermedades Autoinmunes y Reumaticas, CREAR), Rosario, Santa Fe, Argentina.

Epidemiological studies in Latin America suggest indigenous people lack proper healthcare for musculoskeletal (MSK) and rheumatic diseases.

Objectives: This study aimed to estimate the prevalence of MSK disorders and rheumatic diseases in eight Latin American indigenous communities, and to identify which factors influence such prevalence using network analysis and syndemic approach.

Methods: This is a cross-sectional, community-based census study according to Community-Oriented Program for the Control of Rheumatic Diseases methodology. Individuals with MSK pain, stiffness or swelling in the past and/or during the last 7 days were evaluated by participating physicians. A descriptive, univariable and multivariable analysis was performed, followed by a network analysis.

Results: We surveyed 6155 indigenous individuals with a mean age of 41.2 years (SD 17.6; range 18-105); 3757 (61.0%) were women. Point prevalence in rank order was: low back pain in 821 (13.3%); osteoarthritis in 598 (9.7%); rheumatic regional pain syndromes in 368 (5.9%); rheumatoid arthritis in 85 (1.3%); undifferentiated arthritis in 13 (0.2%); and spondyloarthritis in 12 (0.1%). There were marked variations in the prevalence of each rheumatic disease among the communities. Multivariate models and network analysis revealed a complex relationship between rheumatic diseases, comorbidities and socioeconomic conditions.

Conclusions: The overall prevalence of MSK disorders in Latin American indigenous communities was 34.5%. Although low back pain and osteoarthritis were the most prevalent rheumatic diseases, wide variations according to population groups occurred. The relationship between rheumatic diseases, comorbidities and socioeconomic conditions allows taking a syndemic approach to the study.
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http://dx.doi.org/10.1136/annrheumdis-2018-213625DOI Listing
October 2018

Genetic contributions to lupus nephritis in a multi-ethnic cohort of systemic lupus erythematous patients.

PLoS One 2018 28;13(6):e0199003. Epub 2018 Jun 28.

Russell/Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, San Francisco, CA, United States of America.

Objective: African Americans, East Asians, and Hispanics with systemic lupus erythematous (SLE) are more likely to develop lupus nephritis (LN) than are SLE patients of European descent. The etiology of this difference is not clear, and this study was undertaken to investigate how genetic variants might explain this effect.

Methods: In this cross-sectional study, 1244 SLE patients from multiethnic case collections were genotyped for 817,810 single-nucleotide polymorphisms (SNPs) across the genome. Continental genetic ancestry was estimated utilizing the program ADMIXTURE. Gene-based testing and pathway analysis was performed within each ethnic group and meta-analyzed across ethnicities. We also performed candidate SNP association tests with SNPs previously established as risk alleles for SLE, LN, and chronic kidney disease (CKD). Association testing and logistic regression models were performed with LN as the outcome, adjusted for continental ancestries, sex, disease duration, and age.

Results: We studied 255 North European, 263 South European, 238 Hispanic, 224 African American and 264 East Asian SLE patients, of whom 606 had LN (48.7%). In genome-wide gene-based and candidate SNP analyses, we found distinct genes, pathways and established risk SNPs associated with LN for each ethnic group. Gene-based analyses showed significant associations between variation in ZNF546 (p = 1.0E-06), TRIM15 (p = 1.0E-06), and TRIMI0 (p = 1.0E-06) and LN among South Europeans, and TTC34 (p = 8.0E-06) was significantly associated with LN among Hispanics. The SNP rs8091180 in NFATC1 was associated with LN (OR 1.43, p = 3.3E-04) in the candidate SNP meta-analysis with the highest OR among African-Americans (OR 2.17, p = 0.0035).

Conclusion: Distinct genetic factors are associated with the risk of LN in SLE patients of different ethnicities. CKD risk alleles may play a role in the development of LN in addition to SLE-associated risk variants. These findings may further explain the clinical heterogeneity of LN risk and response to therapy observed between different ethnic groups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199003PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023154PMC
December 2018

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.

Hum Mol Genet 2018 07;27(13):2392-2404

Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.

Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared with the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.
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http://dx.doi.org/10.1093/hmg/ddy140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005081PMC
July 2018

Rheumatoid arthritis in the indigenous qom population of Rosario, Argentina: aggressive and disabling disease with inadequate adherence to treatment in a community-based cohort study.

Clin Rheumatol 2018 Sep 19;37(9):2323-2330. Epub 2018 Apr 19.

Hospital Provincial de Rosario, Leandro N Alen 1450, Rosario, Santa Fe, Argentina.

To describe the baseline and follow up epidemiological/clinical characteristics of rheumatoid arthritis (RA) in a community-based cohort of the qom population. RA (ACR criteria) patients identified (n = 40) or not (n = 25) in the previous study were included. Baseline and follow-up visits (3, 6, and 12 months) were performed. Treatment adherence and modification, disability (Health Assessment Questionnaire Disability Index-HAQ-DI), and Disease Activity [DAS-28 (ESR)] were ascertained. At 12 months, complete and incomplete lost to follow-up patients were identified. The estimated RA prevalence was 3%. The patients' mean (SD) disease duration was 110.5 (17.9) and their median delay in diagnosis 30.4 (IQR 52.8) months; mean (SD) age and years of formal education were 39.8 (1.6) and 5.3 (SD 0.3); 58 (89.2%) were female, and 89.2% were seropositive. At baseline, their mean DAS-28 (ESR) was 4.8 (SD 0.9) with 67.7% having high disease activity and 32.3% moderate; 76.9% reported HAQ-DI ≥ 0.8. At 12 months, three patients have died; 13 (20.9%) were "completely" and 19 (30.6%) "incompletely" lost to follow-up. There were favorable changes over time for disease activity (p ˂ 0.001), HAQ-DI (p ˂ 0.001), and treatment modifications (p ˂ 0.001) but no changes in treatment adherence (p = 0.260). The main cause of lost to follow-up was migration. This population has one of the highest RA prevalence rate reported. Patients had an aggressive and disabling disease, with poor adherence to treatment. Improvements of clinical parameters over time were observed.
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http://dx.doi.org/10.1007/s10067-018-4103-5DOI Listing
September 2018

Work disability in Argentinian patients with systemic lupus erythematosus is prevalent and it is due to ethnic, socioeconomic and disease-related factors.

Int J Rheum Dis 2018 Nov 2;21(11):2019-2027. Epub 2018 Apr 2.

Hospital de San Isidro, Ciudad de San Isidro, Argentina.

Objective: To study the prevalence and the associated factors of work disability (WD) in systemic lupus erythematosus (SLE) patients.

Methods: A sample of 419 SLE patients from an observational cross-sectional multicenter study was included. Sociodemographic features, disease characteristics, comorbidities, quality of life, unhealthy behaviors, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not being able to work because of SLE. To identify variables associated with work disability, two different multivariate regression models using a stepwise backward method were performed.

Results: Prevalence of WD due to SLE was 24.3%. Eighty-nine percent were female and 51% were Caucasians. Mean disease duration was 8.9 ± 7.2 years, and median System Lupus International Collaborating Clinics/American College of Rheumatology damage index SLICC-SDI was 1.5 (range 0-17). In stepwise multivariate logistic regression, living below the poverty line (odds ratio [OR] = 4.65), less than 12 years of education (OR = 2.84), Mestizo ethnicity (OR = 1.94) and SLICC-SDI (OR = 1.25) were predictors of WD. A second model was performed including patient-derived measures; in this model sedentary lifestyle (OR = 2.69) and lower emotional health domain score of the Lupus Quality of Life (LupusQoL) questionnaire (OR = 1.03) were found to be associated to WD and a higher score in LupusQoL physical health domain (OR = 0.93) was protective.

Conclusion: The prevalence of WD in Argentinian SLE patients was 24.3%. WD was associated with ethnic (Mestizo), socioeconomic (poverty) and disease-related factors. Patient-related outcomes such us sedentary lifestyle and poor emotional quality of life were also associated with WD.
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http://dx.doi.org/10.1111/1756-185X.13269DOI Listing
November 2018

Remission or low disease activity as a target in systemic lupus erythematosus.

Ann Rheum Dis 2019 01 8;78(1):e3. Epub 2018 Jan 8.

Department of Medicine, Division of Clinical Immunology and Rheumatology, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.

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http://dx.doi.org/10.1136/annrheumdis-2017-212876DOI Listing
January 2019

Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis.

J Rheumatol 2017 Dec 1;44(12):1804-1812. Epub 2017 Nov 1.

From the Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Departamento de Inmunología y Reumatología, Hospital General de Occidente y Universidad de Guadalajara, Zapopan; Unidad de Investigación "Dr. Mario Alvizouri Muñoz" Hospital General "Dr. Miguel Silva," Secretaría de Salud de Michoacán, Morelia; Servicio de Reumatología del Departamento de Medicina Interna, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González," Universidad Autonoma de Nuevo León, Monterrey; Departamento de Reumatología, Hospital General de Culiacán, Culiacán; Unidad de Reumatología, Hospital General de México "Dr. Eduardo Liceaga"; Unidad de Biología Molecular y Medicina Genómica from Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Provincial de Rosario; Instituto Lucha Antipoliomielítica de Rosario (ILAR); Hospital Escuela Eva Perón, Granadero Baigorria; Hospital José Maria Cullen; Hospital J.B. Iturraspe, Santa Fe; Hospital San Martín, Paraná; Hospital Privado de Córdoba; Hospital Italiano de Córdoba; Instituto Reumatológico Strusberg, Córdoba; Hospital Cosme Argerich; Hospital Italiano de Buenos Aires; Organización Médica Integral; Centro de Educación Médica e Investigaciones Clínicas (CEMIC); Instituto de Rehabilitación Psicofísica (IREP); Hospital Bernardino Rivadavia; Hospital de Clínicas de Buenos Aires, Buenos Aires; H.I.G.A. San Martín, La Plata; H.I.G.A. Oscar E. Alende, Mar del Plata; Centro Medico Privado de Reumatología; FUNIPSE, San Miguel de Tucumán, Tucumán; Hospital Interzonal San Juan Bautista, Catamarca; Hospital G. Rawson, San Juan; Sanatorio Parque, Rosario, Argentina; Facultad Medicina Occidente, and Facultad de Medicina Campus Centro, Universidad de Chile, Santiago de Chile, Chile; Servicio de Reumatología, Hospital Nacional Guillermo Almenara I, EsSalud y Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; GENYO, Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica, Granada, Spain; Unit of Chronic Inflammatory Diseases, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Objective: To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America.

Methods: Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history.

Results: Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (p < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (p = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment.

Conclusion: Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.
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http://dx.doi.org/10.3899/jrheum.160485DOI Listing
December 2017