Sexto reporte de eventos adversos con tratamientos biológicos en Argentina: Informe del registro BIOBADASAR / Sixth report of adverse events with biological treatments in Argentina: Report of the BIOBADASAR registry

Objetivo: Actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018. Resultados: Se registraron 4656 pacientes, 6234 tratamientos [3765 casos (terapia con biológicos) y 2469 controles (terapia no biológicos)]. Se interrumpió el tratamiento en el 44,6% en los casos vs. 27,9% en los controles. Causa principal de discontinuación fue por ineficacia (40% casos vs. 32% controles). Se presentaron 3154 eventos adversos (2230 en casos vs. 924 en controles), de los cuales el 13,6% fueron graves (9,8% en casos y 3,7% en controles). El evento adverso (EA) más frecuente en ambos grupos fueron las infecciones (43,56% en casos vs. 34,31% en los controles, RR: 3,42; IC 95%: 3,02-3,88), y de ellas las de vías aéreas superiores (14,5%). Las neoplasias se presentaron en 78 casos vs. 45 en controles (RR: 1,98; IC 95%: 1,37-2,86). Conclusiones: En este sexto reporte no se observan tendencias diferentes sobre seguridad, duración y causas de interrupción del tratamiento respecto a informes previos. Las infecciones fueron el principal EA y la ineficacia, seguido por EA y la pérdida de pacientes las principales causas de suspensión del tratamiento. El advenimiento de nuevos agentes biológicos y la necesidad de control en seguridad a largo plazo, fortalece el uso de este tipo de registro.

Objective: Update the results of the BIOBADASAR registry on safety, duration and causes of treatment interruption after 8 years of follow-up. Methods: BIOBADASAR is a safety record of biological therapies established by the Argentine Society of Rheumatology. The description of BIOBADASAR 3.0 is presented, a cohort of 53 centers in Argentina followed prospectively from August 2010 to January 2018. Results: 4656 patients were registered, 6234 treatments [3765 cases (therapy with biologicals) and 2469 controls (non-biological therapy)]. Treatment was interrupted in 44.6% in cases vs. 27.9% in controls. Main cause of discontinuation was due to inefficiency (40% cases vs. 32% controls). There were 3154 adverse events (2230 in cases vs. 924 in controls), of which 13.6% were tombs (9.8% in cases and 3.7% in controls). The most frequent adverse event (AE) in both groups were infections (43.56% in cases vs. 34.31% in controls, RR: 3.42, 95% CI: 3.02-3.88), and the upper airway pathways (14.5%). Neoplasms were published in 78 cases versus 45 controls (RR: 1.98, 95% CI: 1.37-2.86). Conclusions: In this article, there are no different trends regarding safety, duration and causes of interruption of treatment compared to previous reports. Infections were the main causes of treatment discontinuation. The advent of new biological agents and the need for control over long-term security, strengthens the use of this type of registration.

Características de los tratamientos biológicos en enfermedades reumáticas en Argentina: quinto informe del registro BIOBADASAR / Features of rheumatic diseases biological treatments in Argentina: BIOBADASAR fifth report

Introducción: El proyecto BIOBADASAR (Registro argentino deeventos adversos con tratamientos biológicos en reumatología)comenzó en agosto de 2010, para recabar información a largo plazosobre los eventos adversos en tratamientos biológicos en pacientescon enfermedades reumáticas en la práctica clínica cotidiana enArgentina.Pacientes y método: Se registraron datos de cada paciente,tratamientos y acontecimientos adversos relevantes o importantes.Los pacientes debían tener enfermedad diagnosticada y tratadacon un agente biológico. Cada caso se comparó con un control:un paciente con tratamiento no biológico con característicasdemográficas similares. Se analizaron los datos con análisis de lavarianza, con test de t de Student, Mann Whitney, test chi2, o testexacto de Fisher. El análisis de supervivencia de los tratamientoshasta su discontinuación o interrupción se realizó con el método deKaplan-Meier y test log-rank...

Background: BIOBADASAR (Argentine Registry of Adverse Eventsin Biological Treatments in Rheumatology) was started in August2010 to obtain long-term information of patients with rheumatic diseases,treatments and adverse events in everyday clinical practice.Patients and methods: Data on patients’ demographics,treatments and adverse events were collected. Patients had a diagnosisof a rheumatic disease and were treated with biological agent.To compare information, a control group was included, consisting ofpatients treated with similar demographic characteristics but treatedwith a non-biological agent. Data were analysed with Anova,Student´s t, Mann Whitney, chi2, Fisher´s exact tests, as appropriate.Survival analysis of treatments was performed with Kaplan-Meiercurves and log-rank test...

Tercer reporte de eventos adversos con tratamientos biológicos en Argentina. Informe de registro biobadasar / Thrid report of adverse events with biologics in Argentina. Report from biobadasar registry

Introducción: BIOBADASAR (Registro Argentino de Eventos Adversos con Tratamientos Biológicos en Reumatología) comenzó en agosto de 2010. La importancia de este registro es mostrar datos locales que, probablemente, puedan diferir de otros registros. El objetivo es comunicar los resultados del tercer reporte de BIOBADASAR. Métodos: Todos los pacientes con enfermedades reumáticas que requirieron tratamiento con agentes biológicos y pacientes controles sin estos tratamientos fueron incluidos en la base de datos provenientes de 32 centros participando a lo largo de la Argentina. Tres áreas de datos son analizados: características de los pacientes, tratamientos y eventos adversos...

Introduction: BIOBADASAR (Argentine Registry of Adverse Events with Biological Treatments in Rheumatology) began in August 2010. The importance of this registry is to show local data that may probably differ from other registries. The objective is to communicate the results of the third BIOBADASAR report. Methods: All patients with rheumatic diseases who required treatment with biological agents and control patients without these treatments were included in the database from 32 participating centers throughout Argentina. Three areas of data are analyzed: patient characteristics, treatments and adverse events...

Primer reporte de eventos adversos de tratamientos biológicos en Argentina. Informe de Registro BIOBADASAR / First report of adverse events for biologic treatments in Argentine. BIOBADASAR Register

Introducción: En la actualidad existe gran cantidad de pacientes sometidos a tratamiento con agentes biológicos en enfermedades reumatológicas y se desconocen los efectos adversos predominantes, así como la eficacia y tasa de discontinuación de nuestros pacientes en dichos tratamientos. Objetivo: Comunicar los primeros resultados de BIOBADASAR, Registro Argentino de Acontecimientos Adversos ocasionados por el Uso de Agentes Biológicos en Reumatología. Métodos: Participan del registro 56 centros de Reumatología de Argentina. Se requiere el ingreso de un paciente no tratado con agentes biológicos por cada paciente expuesto ingresado en el registro. Datosdesde el 1 de agosto de 2010 hasta 1 abril 2011. Las variables categóricasse calcularon con chi cuadrado y las continuas con T student. Se calcularon porcentajes de incidencia y por persona/año. Resultados: Se incorporaron 966 pacientes (1132 tratamientos). Mujeres 763 (79%) y hombres 203 (21%). La edad media fue 52 años (3-88); 543 pacientes (56%) fueron tratados con agentes biológicos (casos) y 423 (44%) fueron no tratados con agentes biológicos (controles). 786 pacientes tenían artritis reumatoidea (81,4%) y 79 artritis psoriásica (8,2%), entre otros diagnósticos. La media de tiempo de evolución de enfermedad fue 11 años para los casos y 8,25 años para los controles. El fármaco biológico más utilizado fue el etanercept con 348 tratamientos (50%) y una supervivencia al tratamiento en años cuya media fue 2,90 seguido por el adalimumab con 158 tratamientos (22,7%) y una supervivencia al tratamiento en años cuya media fue 2,15. La causa más frecuente de interrupción de tratamiento en los casos fue ineficacia (42,1%) seguido por eventos adversos (32%).

Systemic lupus erythematosus: mortality and survival in Argentina. A multicenter study.

OBJECTIVE: To analyze the factors associated with mortality, survival and causes of death in patients with systemic lupus erythematosus (SLE) in Argentina. PATIENTS AND METHOD: A series of 366 patients with SLE (45 men and 321 women), mean age 29 y (range 11-70 y) and mean disease duration 6 y, was evaluated from 1990 to 1998. A total of 57 clinical, serological and therapeutic variables were studied. RESULTS: Five- and 10-year survival was 91% and 85% respectively. Forty four patients died (12%): 54% due to sepsis and 32% due to active SLE. Mortality risk factors included heart involvement CRR 3.82), hyperlipidemia (RR 2.72), renal damage (RR 2. 62), infections (RR 2.44), lung disease (RR 2.20) and myositis (RR 2. 07). High-dose prednisone (RR 3.4) or cyclophosphamide (RR 9.19) treatments increased the risk of sepsis (P=0.003) as a cause of death. However, corticosteroids, antimalarial agents and accumulated cyclophosphamide doses proved to be protective factors in overall mortality figures (RR <1). CONCLUSIONS: The main risk factors of death in SLE were heart involvement, hyperlipidemia and renal damage. Treatment with steroids, antimalarial agents and cyclophosphamide improved survival. High-dose corticosteroids and cyclophosphamide were associated with sepsis as a cause of death.

[Changes in bone mass and in glucose homeostasis in subjects with high spontaneous fluoride intake]. / Modificaciones en la masa osea y en la homeostasis de la glucosa en residentes de la zona de Bahía Blanca con alta ingesta espontanea de flúor.

This paper reports metabolic data of 24 women and two men, 44-66 years old, ex-residents in an area of endemic fluorosis close to Bahía Blanca city. Fasting fluoremias of these subjects (0.5 to 9.2 microM) and daily urinary fluoride excretion (> 60 mumoles/day) are characteristics of zones with endemic fluorosis. Bone mineral density (BMD) at the lumbar spine (L2-4 1330 +/- 41 mg/cm2) and femoral neck (1045 +/- 10 mg/cm2) were significantly above average of normal subjects of the same age and sex. A significant correlation was observed between the daily excretion of fluoride and BMD L2-4 (r = 0.43, P < 0.05). The Area Under the Curve of insulin during a standard glucose tolerance test showed an inverse relationship with fluoremia. This observation coincides with experiments published elsewhere indicating that fluoride intake at concentrations 5 microM or greater, inhibits the secretion of insulin.

Atlantoaxial subluxation in systemic lupus erythematosus: further evidence of tendinous alterations.

We prospectively determined the frequency of atlantoaxial subluxation in a group of patients with systemic lupus erythematosus (SLE) and analyzed its relationship with tendinous laxity, Jaccoud's syndrome and other features of the disease. Five of 59 patients (8.5%) had atlantoaxial subluxation. No patient presented atlantoaxial subluxation in neutral lateral cervical radiographs but all 5 had anterior atlantoaxial subluxation in full flexion films; one patient also had lateral subluxation. The 5 patients with atlantoaxial subluxation were compared with the remaining 54. Mean SLE disease duration was longer in patients with atlantoaxial subluxation (12 years) than in those without (6.6 years) (p less than 0.01). Jaccoud's syndrome, patellar tendon elongation and articular hypermobility were significantly more frequent in patients with atlantoaxial subluxation. The presence or history of arthritis failed to distinguish patients with and without atlantoaxial subluxation, while chronic renal failure and increased serum parathyroid hormone levels were significantly associated to the presence of atlantoaxial subluxation. We suggest that atlantoaxial subluxation is further evidence of tendinous alterations seen in patients with SLE.

Tendinous laxity and Jaccoud's syndrome in patients with systemic lupus erythematosus. Possible role of secondary hyperparathyroidism.

Fourteen of 52 unselected patients with systemic lupus erythematosus (SLE) (27%) had ligamentous derangement demonstrated by either Jaccoud's syndrome and/or patellar tendon elongation. Three cases had only Jaccoud's syndrome, 4 isolated patellar tendinous laxity, while the remaining 7 presented both findings. Jaccoud's syndrome and/or tendinous laxity were not associated to an increased frequency of arthritis, corticosteroid therapy or a longer disease duration, but significantly associated with increased serum PTH levels secondary to chronic renal failure. Hyperparathyroidism secondary to chronic renal failure should, therefore, be considered a potential factor contributing to the development of Jaccoud's syndrome and/or tendinous laxity in patients with SLE.