Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Experiencia sobre el proceso de salud-enfermedad-atención en pacientes con artritis reumatoidea pertenecientes a la comunidad Wichí de Misión Chaqueña "El Algarrobal", Salta / Experience on the health-disease-care process in patients with rheumatoid arthritis belonging to the Wichí community of Mission Chaqueña "El Algarrobal", Salta

Introducción: se ha reportado que la prevalencia de artritis reumatoidea (AR) en la comunidad Wichí representa la más alta informada por el Grupo Latinoamericano para el Estudio de las Enfermedades Reumáticas en los Pueblos Originarios (GLADERPO). El objetivo de este estudio fue describir la experiencia sobre el proceso de salud-enfermedad-atención de pacientes con AR de la comunidad Wichí de Misión Chaqueña "El Algarrobal", Salta. Materiales y métodos: estudio narrativo. Diseño de corte etnográfico. Se realizaron entrevistas semi-estructuradas y observaciones registradas. Se utilizaron guías de entrevistas y observación. Los aspectos incluidos fueron: concepción del proceso salud-enfermedad, percepción de la AR en la vida diaria, el acceso al sistema de salud, utilización de recursos tradicionales y de medicina tradicional. Resultados: se realizaron 10 entrevistas. Los aspectos más relevantes fueron la concepción del proceso salud-enfermedad asociado al trauma social pasado y al concepto de voluntad Wichí. Se evidenció la combinación de estrategias para mejorar el dolor (biomedicina, medicina tradicional y acompañamiento religioso). Además, se observó una relación unidireccional con el sistema de salud. Conclusiones: la AR es una enfermedad con un impacto negativo en la comunidad Wichí. Se requieren otras actividades, desde otras disciplinas, para mejorar el acceso al sistema de salud y la continuidad de los tratamientos.

Introduction: the prevalence of rheumatoid arthritis (RA) in the Wichí community has already been published, representing the highest reported by the Grupo Latinoamericano para el Estudio de las Enfermedades Reumáticas en los Pueblos Originarios (GLADERPO). The objective was to describe the experience of the health-disease-care process of patients with RA from the Wichí community of Misión Chaqueña "El Algarrobal", Salta. Materials and methods: study with ethnographic design. Semi-structured interviews and recorded observations were conducted. Interview and observation guides were used. The aspects included were: conception of the health-disease process; perception of RA in daily life, access to the health system, use of traditional resources and traditional medicine. Results: ten interviews were conducted. The most relevant aspects were the conception of the health-disease process, associated with past social trauma and the concept of "Wichí good will". The combination of strategies to improve pain (biomedicine, traditional medicine and religious accompaniment) was evidenced. In addition, a unidirectional relationship with the health system was observed. Conclusions: RA is a disease with a negative impact on the Wichí community. Other activities from other disciplines are necessary to improve access to the health system and continuity of treatment.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Accelerated atherosclerosis and cardiovascular disease in systemic lupus erythematosus / Aterosclerosis acelerada y enfermedad cardiovascular en el lupus eritematoso sistémico

ABSTRACT Cardiovascular disease (CVD), particularly coronary heart disease and stroke, is one of the most important causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The increased prevalence of CVD and subclinical atherosclerosis, even after adjustment for traditional risk factors, are well established. Several associations with disease-related clinical, genetic and immunological features have been identified. The SLE-specific stratification algorithms with emphasis on composite risk-assessment scores including both traditional risk factors and novel biomarkers is recommended. The clinical complexity of accelerated atherosclerosis will most likely require an integrated approach for the identification, treatment, and intensive study into this aspect of SLE that will ultimately lead to improved cardiovascular outcomes for these patients.

RESUMEN La enfermedad cardiovascular (ECV), en particular la enfermedad coronaria y el ictus, es una de las causas más importantes de morbimortalidad en pacientes con lupus eritematoso sistémico (LES). El aumento en la prevalencia de la ECV y de la aterosclerosis subclínica, aun después del ajuste de los factores de riesgo tradicionales, está claramente establecida. Se han identificado diversas asociaciones con características clínicas, genéticas e inmunológicas relacionadas con la enfermedad. Se recomienda el uso de los algoritmos de estratificación específicos para el LES, con énfasis en los puntajes compuestos de evaluación de riesgo, incluyendo tanto los factores de riesgo tradicionales como los nuevos biomarcadores. La complejidad clínica de la aterosclerosis acelerada muy probablemente requerirá un abordaje integral para la identificación, el tratamiento y el estudio intensivo de este aspecto del LES, que en última instancia permita obtener mejores desenlaces cardiovasculares en estos pacientes.

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

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.

Asociación entre Artritis Reumatoidea y otras enfermedades autoinmunes / Association between Rheumatoid Arthritis and other autoimmune diseases

Objetivos: Determinar la frecuencia de enfermedades autoinmunes (EAI) en pacientes con Artritis Reumatoidea (AR) y comparar la frecuencia de EAI entre pacientes con AR y sin AR ni otra EAI reumatológica. Material y Métodos: Estudio multicéntrico, observacional, analítico, retrospectivo. Se incluyeron pacientes consecutivos con AR (ACR/EULAR 2010) y como grupo control pacientes con diagnóstico inicial de Osteoartritis primaria (OA). Resultados: Se incluyeron 1549 pacientes: 831 con AR (84% mujeres, edad media 55.2 años [DE 13.6]) y 718 con OA (82% mujeres, edad media 67 años [DE 11.1]). La frecuencia de EAI en el grupo AR fue del 22% (n=183). Estos presentaron mayor frecuencia de EAI reumatológicas (9.4 vs 3.3%, p< 0.001), y menor frecuencia de EAI no reumatológicas que aquellos con OA (15.3 vs 20.5, p=0.007). La EAI reumatológica más prevalente fue el Síndrome de Sjögren, el cual fue más frecuente en el grupo AR (87.2 vs 29.2%, p< 0,001). La frecuencia de EAI reumatológicas en los pacientes con AR fue mayor en la forma erosiva (11 vs 6.8%, p=0.048). Conclusión: La frecuencia de EAI en los pacientes con AR fue del 22%, en quienes predominaron las de etiología reumatológica mientras que, las no reumatológicas predominaron en pacientes con OA.

Objectives: To determine the frequency of autoimmune diseases (AID) in Rheumatoid Arthritis (RA) patients and to compare this frequency between patients with and without RA or other rheumatologic AID. Methods: Multicenter, observational, analytical, retrospective study. Consecutive patients with diagnosis of RA (ACR/EULAR 2010) were included. Patients with initial diagnosis of primary ostearthritis (OA) were used as control group. Results: A total of 1549 patients were included: 831 RA (84% women, mean age 55.2 [±13.6]) and 718 OA (82% women, mean age 67 [± 11.1]). The frequency of AID in the RA group was 22% (n=183). RA patients showed higher frequency of rheumatologic AID (9.4 vs 3.3%, p< 0.001), and lower frequency of non-rheumatologic AID than OA patients (15.3 vs 20.5%, p= 0.007). The most prevalent rheumatic AID was Sjögren's Syndrome, which was more frequent in the AR group (87.2 vs 29.2%, p<0.001). The frequency of rheumatologic AID in RA patients was higher in those with erosive RA (11 vs 6.8%, p=0.048). Conclusion: The frequency of AID in RA patients was 22%. Rheumatologic AID were more frequent in RA patients, whereas non-rheumatologic AID prevailed in OA patients.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

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

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 (pBonferroni < 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 (pBonferroni = 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.

Prevalence of musculoskeletal disorders and rheumatic diseases in the indigenous Qom population of Rosario, Argentina.

This study aimed to estimate the prevalence of musculoskeletal disorders and rheumatic diseases among the indigenous Qom (Toba) population in the city of Rosario, Santa Fe, Argentina. An analytical cross-sectional study using methodology of the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) was performed. Subjects ≥18 years of age were interviewed by advanced students of medicine and nursing, bilingual translator-facilitators, and coordinators. Individuals with musculoskeletal pain (positive cases) were evaluated sequentially for 7 days by internists and rheumatologists for diagnosis and treatment. The study included 1656 individuals (77 % of the census population). Of these, 1020 (61.5 %) were female, with mean age of 35.3 (SD 13.9) years, and 1028 (62.0 %) were bilingual. The public health care system covers 87.1 % of the population. Musculoskeletal pain in the previous 7 days and/or at some time during their life was present in 890 subjects (53.7 %). Of those with pain in the last 7 days, 302 (64.1 %) subjects had an Health Assessment Questionnaire Disability Index (HAQ-DI) score ≥0.8. The most frequent pain sites were lumbar spine (19.3 %), knees (13.0 %), and hands (12.0 %). The prevalence of rheumatic diseases was as follows: mechanical back pain (20.1 %), rheumatic regional pain syndrome (2.9 %), osteoarthritis (4.0 %) rheumatoid arthritis (2.4 %), inflammatory back pain (0.2 %), systemic sclerosis (0.1 %), Sjögren syndrome (0.1 %), fibromyalgia (0.1 %), mixed connective tissue disease (0.06 %), and systemic lupus erythematosus (0.06 %). The prevalence of musculoskeletal disorders was 53.7 % and rheumatic diseases 29.6 %. Rheumatoid arthritis prevalence was 2.4 % using COPCORD methodology, one of the highest reported at present.

Golimumab, a human anti­tumor necrosis factor monoclonal antibody, injected subcutaneously every 4 weeks in patients with active rheumatoid arthritis who had never taken methotrexate: 1-year and 2-year clinical, radiologic, and physical function findings of a phase III, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To assess 2-year golimumab efficacy/safety in patients with active rheumatoid arthritis (RA) who had never taken methotrexate (MTX). METHODS: RA patients who had never taken MTX (n = 637) were randomized (1:1:1:1) to placebo + MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group 3), or golimumab 100 mg + MTX (group 4) every 4 weeks. Nonresponders based on week 28 swollen/tender joint counts changed treatment as follows: group 1 added golimumab 50 mg, group 2 added MTX, group 3 increased golimumab to 100 mg, and group 4 had no change. Most group 1 patients (85%) initiated golimumab 50 mg + MTX at week 28 or subsequently at week 52. After the last patient completed week 52 and blinding was broken, the investigator could escalate golimumab to 100 mg and/or adjust MTX. The co­primary end points (week 24 American College of Rheumatology criteria for 50% improvement [ACR50] response and week 52 change in Sharp/van der Heijde score [SHS]) have been published previously. We now detail week 52 major secondary end points (Health Assessment Questionnaire [HAQ] disability index [DI] scores and SHS among patients with a baseline C-reactive protein [CRP] level >1.0 mg/dl) and week 104 findings. RESULTS: At week 52 for combined groups 3 and 4 versus group 1, the respective proportions of patients achieving ACR20 and ACR50 responses were 63.2% versus 51.9% (P = 0.017) and 45.3% versus 35.6% (P = 0.044). Respective week 52 mean HAQ DI improvements were 0.70 versus 0.58 (P = 0.053); mean SHS changes were 0.41 versus 1.37 (P = 0.006) among all patients and 0.74 versus 2.16 (P = 0.003) in patients with a CRP level >1.0 mg/dl. Improvements were maintained through week 104. Golimumab + MTX for 2 years yielded statistically less radiographic progression than initial MTX or golimumab 100 mg monotherapy. Golimumab safety profiles through weeks 24, 52, and 104 were generally consistent with those observed in other golimumab studies. CONCLUSION: In RA patients who had never taken MTX, up to 2 years of golimumab + MTX yielded sustained improvements in clinical signs/symptoms, physical function, and radiographic progression.

Trans-ancestral studies fine map the SLE-susceptibility locus TNFSF4.

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P=1.71 × 10(-34) , OR=1.43[1.26-1.60]) and rs1234317-T (P=1.16 × 10(-28) , OR=1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5' region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5' risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait.

Prevalencia de dislipemia y riesgo cardiovascular elevado en pacientes con artritis reumatoide / Prevalence of dyslipidemia and elevated cardiovascular risk in patients with rheumatoid arthritis

Los objetivos del estudio fueron comparar la frecuencia de riesgo cardiovascular (CV) elevado y dislipemia (DLP) en pacientes con artritis reumatoide (AR) y en controles, identificar variables de la enfermedad asociadas a DLP y estimar el porcentaje de pacientes con AR medicados para DLP. Estudio de corte transversal que incluyó 409 pacientes con AR y 624 controles. El riesgo CV se determinó con las clasificaciones NCEP y SCORE modificados por European League Against Rheumatism (EULAR). Para DLP se utilizó la definición de Adult Treatment Panel III (ATP III). La frecuencia de riesgo CV elevado fue similar en pacientes con AR y controles excepto cuando fue definida por NCEP-EULAR (7% vs. 2%; p = 0.00002). La DLP fue encontrada en el 43% de los pacientes con AR y en el 47% de los controles (p = 0.15). Los pacientes con AR y DLP tuvieron más manifestaciones extra-articulares (36% vs. 24%; p = 0.01) y mayor velocidad de sedimentación globular (VSG) (21 (13-35) vs. 18 (10-30) mm; p = 0.003). El tratamiento recibido para DLP varió según la definición utilizada (11% a 32%). Se encontró mayor riesgo CV en los pacientes con AR solo cuando se definió por NCEP- EULAR. Los pacientes con AR y DLP tuvieron mayor VSG y manifestaciones extra-articulares. La mayoría de los pacientes con AR y DLP no estaban recibiendo tratamiento hipolipemiante.

The objectives of this study were to compare the frequency of dyslipidemia (DLP) and the elevated cardiovascular risk between rheumatoid arthritis (RA) patients and a control group, to identify disease-related factors associated with the presence of DLP and to estimate the frequency of RA patients receiving treatment for DLP. This is a cross sectional study that included 409 RA patients and 624 controls. Cardiovascular (CV) risk was determined using the Framingham score, National Cholesterol Education Program (NCEP) and the Systematic Coronary Risk Evaluation (SCORE) adapted versions according to the European League Against Rheumatism (EULAR) guidelines. DLP was defined according to the Adult Treatment Panel III (ATPIII). The frequency of CV risk was similar in RA patients and controls, except when NCEP-EULAR adapted version for RA was applied (7% vs. 2%; p = 0.00002). A 43% of patients and 47% of controls had DLP (p = 0.15). RA patients with DLP tended to have extra-articular manifestations more frequently (36% vs. 24%; p = 0.01) and higher erythrocyte sedimentation rate (ESR) (21 [13-35] vs. 18 [10-30] mm; p = 0.003). RA patients treated for DLP varied between 11% and 32% according to the definition used. Patients with RA showed an elevated CV risk only when the NCEP-EULAR definition was used. Among RA patients, those with higher ESR and the presence of extra-articular manifestations were more likely to show DLP. The vast majority of patients were not receiving treatment for DLP.

Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome-wide association studies have identified >30 SLE susceptibility genes. One of these genes, TNIP1, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF-κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF-κB pathway. METHODS: We analyzed a dense set of genetic markers spanning TNIP1 and TAX1BP1, as well as the TNIP1 homolog TNIP2, in case-control populations of diverse ethnic origins. TNIP1, TNIP2, and TAX1BP1 were fine-mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European-ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of TNIP1 messenger RNA (mRNA) and ABIN1 protein in Epstein-Barr virus-transformed human B cell lines were analyzed by quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively. RESULTS: We found significant associations between SLE and genetic variants within TNIP1, but not in TNIP2 or TAX1BP1. After resequencing and imputation, we identified 2 independent risk haplotypes within TNIP1 in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of TNIP1 mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression. CONCLUSION: Our results confirm the association signals between SLE and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis.

Novel association of acid phosphatase locus 1*C allele with systemic lupus erythematosus.

The red cell acid phosphatase (ACP1) gene, which encodes a low-molecular-weight phosphotyrosine phosphatase, has been suggested as a common genetic factor of autoimmunity. In the present study, we aim to investigate the possible association of ACP1 with the susceptibility of systemic lupus erythematosus (SLE). A total of 1,546 SLE patients and 1,947 healthy individuals from 4 Caucasians populations were included in the present study. Four single-nucleotide polymorphisms (SNPs) were genotyped in this study: rs10167992, rs11553742, rs7576247, and rs3828329. ACP1*A, ACP1*B, and ACP1*C codominant ACP1 alleles were determined using 2 of the SNPs and analyzed. After the meta-analysis test was performed, a significant association of rs11553742*T was observed (p(pooled) = 0.005, odds ratios = 1.37 [1.10-1.70]), retaining significance after multiple testing was applied (p(FDR) = 0.019). Our data indicate for first time the association of rs11553742*T with increased susceptibility in SLE patients.

Dual effect of the macrophage migration inhibitory factor gene on the development and severity of human systemic lupus erythematosus.

OBJECTIVE: To study the effect of the innate cytokine macrophage migration inhibitory factor (MIF) on the susceptibility and severity of systemic lupus erythematosus (SLE) in a multinational population of 1,369 Caucasian and African American patients. METHODS: Two functional polymorphisms in the MIF gene, a -794 CATT(5-8) microsatellite repeat (rs5844572) and a -173 G/C single-nucleotide polymorphism (rs755622), were assessed for association with SLE in 3,195 patients and healthy controls. We also measured MIF plasma levels in relation to genotypes and clinical phenotypes, and assessed Toll-like receptor 7 (TLR-7)-stimulated MIF production in vitro. RESULTS: Both Caucasians and African Americans with the high-expression MIF haplotype -794 CATT(7)/-173*C had a lower incidence of SLE (in Caucasians, odds ratio [OR] 0.63, 95% confidence interval [95% CI] 0.53-0.89, P = 0.001; in African Americans, OR 0.46, 95% CI 0.23-0.95, P = 0.012). In contrast, among patients with established SLE, reduced frequencies of low-expression MIF genotypes (-794 CATT(5)) were observed in those with nephritis, those with serositis, and those with central nervous system (CNS) involvement when compared to patients without end-organ involvement (P = 0.023, P = 0.005, and P = 0.04, respectively). Plasma MIF levels and TLR-7-stimulated MIF production in vitro reflected the underlying MIF genotype of the studied groups. CONCLUSION: These findings suggest that MIF, which has both proinflammatory properties and macrophage and B cell survival functions, exerts a dual influence on the immunopathogenesis of SLE. High-expression MIF genotypes are associated with a reduced susceptibility to SLE and may contribute to an enhanced clearance of infectious pathogens. Once SLE develops, however, low-expression MIF genotypes may protect from ensuing inflammatory end-organ damage.