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.

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.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

[The repeated biopsy in patients with lupus nephritis]. / El rol de la biopsia repetida en pacientes con nefritis lúpica.

We retrospectively studied patients with SLE according to ACR criteria, with NL who underwent a repeat renal biopsy from 2005 to 2012. We analyzed the main indications of renal biopsies, the histopathological Class and activity and chronicity changes. RESULTS The total number of patients with NL was 120, of which 18 (15%) patients underwent repeat renal biopsy, 18 had 2 renal biopsies and 6 had 3 biopsies. 3 (16.7%) patients were smokers; 1 (5.6%) had a history of previous DBT, 2 (11.1%) had a history of hypertension; and 3 (16.7%) patients had previous obesity. The duration of SLE was 15 ± 96 months; the time between the 1st and the 2nd biopsy was 45 ± 11 months and the time between the 2nd and 3rd biopsy was 56 ± 12 months. Indications for repeat biopsy were proteinuria in 10 biopsies (41.6%); proteinuria with impaired renal function in 2 biopsies (8.3%); proteinuria with pathological urine sediment in 8 (33.3%); . and pathological proteinuria with pathological urine sediment and impaired renal function in 4 biopsies (16.6%) The most frequent histological changes found between first and repeat biopsies were class IV to class III: 2 (8.2%) ; Class IV to Class IV: 8 (33.3%), class IV to class III + V: 2 (8.2%); class IV to class IV + V 3 (12.5%); class IV to class V: 2 (8.2%). Changes in NL biopsies with proliferative activity and chronicity indices (A / C) were: A to A / C: 7 (29.1%), A / C to A / C: 7 (29.1%). The immunosuppressive therapy was increased in 79.1% and 16.6% remained without changes. 20% patients received cyclophosphamide 1 g every 30 days, 26% Cyclophosphamide 500 mg every 15 days, 23% induction therapy with mycophenolate mofetil; 23% with Rituximab; 8% Cyclosporin A. Maintenance therapy with mycophenolate mofetil was performed in 87.5%; azathioprine in 1 case. Hydroxychloroquine was used in all cases.

Se estudiaron retrospectivamente pacientes con diagnóstico de lupus eritematoso sistémico (LES) de acuerdo a criterios ACR 1982, con nefritis lúpica (NL) durante el período comprendido desde 2005 al 2012 y que fueran sometidos a una biopsia renal repetida. El número total de pacientes con NL atendidos fue de 120, de los cuales 18 (15%) pacientes fueron sometidos a biopsia renal repetida, 18 con 2 biopsias renales y 6 con 3 biopsias. 3 (16,7%) de los pacientes fueron fumadores; 1 (5,6%) poseía antecedentes de DBT previa, 2 (11,1%) poseían antecedentes de HTA; y 3 (16,7%) pacientes tenían obesidad previa. El tiempo de diagnóstico de LES al momento del estudio fue de 96 meses ± 15; el tiempo transcurrido entre la 1° y la 2° biopsia fue de 45 ± 11 meses y el tiempo entre la 2° y 3° biopsia fue de 56 ± 12 meses. Las indicaciones de la biopsia repetida fueron proteinuria en 10 biopsias (41,6%); proteinuria con alteración de la función renal en 2 biopsias (8,3%); proteinuria con sedimento patológico en 8 biopsias (33,3%); y proteinuria con sedimento patológico y alteración de la función renal en 4 biopsias (16,6%). Los cambios histológicos más frecuentes encontrados entre las primeras y las biopsias repetidas fueron: de clase IV a clase III: 2 (8,2%); clase IV a clase IV: 8 (33,3%), clase IV a clase III+V: 2 (8,2%); clase IV a clase IV+V: 3 (12,5%); clase IV a clase V: 2 (8,2%). Los cambios en las biopsias de NL proliferativas con índices de actividad y cronicidad (A/C) fueron: de A a A/C: 7 (29,1%), A/C a A/C: 7 (29,1%). La intensidad de la terapia inmunosupresora aumentó en 79,1%, se mantuvo el tratamiento inmunosupresor en 16.6%. Con respecto al cambio de medicación 7 (20%) pacientes recibieron Ciclofosfamida 1 gr cada 30 días, 9 (26%) Ciclofosfamida 500 mg cada 15 días, 8 (23%) tratamiento de reinducción con Micofenolato mofetil; Rituximab 8 (23%); y 3 (8%) Ciclosporina A. El tratamiento de mantenimiento se realizó con micofenolato mofetil en 23 casos (55%); con azatioprina en 11 (26%) casos; ciclosporina en 3 (7%) oportunidades y rituximab en 5 (12%). En todos los casos se utilizó hidroxicloroquina.