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...

[Bacterial endocarditis caused by salmonella in systemic lupus erythematosus]. / Endocarditis por salmonella en lupus eritematoso sistemico.

INTRODUCTION: Patients with SLE (Systemic Lupus Erythematosus) are prompt to develop infections with significant morbidity and mortality. The intravascular infection due to salmonella is a rare complication of difficult diagnosis and poor prognostic. OBJECTIVE: We report two cases of bacterial endocarditis due to salmonella in SLE patients. CLINICAL CASES: We report two cases of bacterial endocarditis caused by Salmonella in a patient with SLE, one with recent onset of mellitus diabetes and other with chronic renal failure. Despite of antibiotic treatment with fluoroquinolone and a third-generation cephalosporin, the patient required surgical intervention. CONCLUSION: Salmonella infection should be suspected in SLE patients in order to make earlier diagnosis and treatment.

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%).

[Ventricular diastolic dysfunction in rheumatoid arthritis]. / Disfunciondiastólica ventricular izquierda en la artritis reumatoidea.

UNLABELLED: Rheumatoid arthritis ( RA) is a chronic and systemic articular inflammatory disease, often associated with cardiac manifestations. However, cardiac involvement in RA is not always symptomatic. Previous studies reported high mortality rates for RA and that it was dependent on concurrent heart dis-ease. Myocardial infarction and inflammation have been reported in about 2% of the patients in autopsy studies. The earliest deterioration in cardiac disease is in diastolic function. OBJECTIVE: the aim of this study is to evaluate the ventricular diastolic dysfunction in patients with RA and its relation with the duration of the disease. PATIENTS AND METHODS: Thirty-two RA patients who attended the rheumatology unit at Hospital Cordoba during 2004 participated in this study. A control group was formed by thirty two healthy adults of matched sex and age. RA was diagnosed according to 1987 ACR criteria. None of them had diabetes mellitus, systemic hypertension, chronic lung disease, congenital cardiac malformation, coronary artery disease, arrhytmia or valvular heart disease. Two-dimensional, M-mode, pulsed and color Doppler echocardiography were performed on all these subjects by the same examiner. Diastolic dysfunction was defined when the E/A ratio was <1 (E wave velocity decreased, A wave velocity increased) , and desaceleration time (DT) and isovolumic relaxation time (IRT) were prolonged. Ap-value < 0.05 was considered as significant. RESULTS: The mean ages were 48,38 11,08 for patients and 46,81 9,96 for the control group.There were no significant differences between age, sex, heart rate, and systolic and diastolic blood pressure between RA patients and controls. Higher proportion of RA patients had E/A ratio < 1compared with the controls ( p<00001). The mean IRT value was significantly longer than in controls ( 83,59 1 13,82 vs 74,41 i 15,14 p<0.01). There was no correlation between the duration of illness and E/A ratio and IRT ( p=0.70, p=0.13). CONCLUSION: Diastolic function was impaired in patients with RA. There was no relation between some of the parameters of ventricular diastolic function and disease duration. These findings suggest a subclinical myocardial involvement in RA patients.

[Security of the combined treatment of methotrexate and leflunomide in patients with rheumatoid arthritis]. / Seguridad del tratamiento combinado de metotrexato y leflunomida en pacientes con artritis reumatoidea.

UNLABELLED: Rheumatoid Arthritis (RA) is a chronic disease leading to functional impairment and early mortality. Treatment with disease-modifying antirheumatic drugs have shown to achieve disease remission and improves its evolution. The use of combined therapy should have a biological efficacy, no increased toxicity and have an acceptable dose interval. Also, it should begin its action quickly and be cost-effective. AIMS: to assess the security of the combined treatment with Methotrexate (MTX) and Leflunomide (LF) in patients with Rheumatoid Arthritis (RA) and to evaluate whether the dose and route of MTX administration influence on the toxicity. PATIENTS AND METHODS: Patients with RA who fulfilled ACR criteria and they attended to the Rheumatology Unit at Córdoba Hospital in the last 2 years were assessed. All the patients that received combined treatment with MTX in doses from 7.5 mg to 25 mg weekly orally (PO) or intramuscularly (i.m.) that started LF treatment in doses of 20 mg/day due to disease activity persistence were retrospectively assessed. Patients having at least 6 months of combined treatment were included. Data on treatment and adverse events were collected. They were evaluated at the beginning, at 6 and 12 months of treatment. The presence of adverse events as well as the stop of combined treatment was evaluated at 6 and 12 months of treatment. Adverse events in patients with oral and i.m. MTX treatment and in different doses were compared for the analyses. P<0.05 was considered significant. RESULTS: 62 patients with a mean age of 54 were included. 89% were female and had positive rheumatoid factor and 83% had radiological erosions. Eighty eight percent were in doses of 15 mg MTX, 4.9% with 10 mg and 25 mg at the beginning of LF treatment. Twenty four percent suffered from adverse events and 33% left the medication by 6 months. Among adverse events, 6 patients had diarrhea, 5 increased hepatic enzymes, 3 alopecia, 3 weight loss, and 2 had anemia and leucopenia. Eight patients stopped the medication in 6 months, but only 5 did because of adverse events. There was not significant statistical difference in adverse events between patients with different dose or routes of administration of MTX. CONCLUSIONS: The presence of adverse events in MTX and LF combined treatment was low and it developed during the first 6 months of treatment in our patients. The MTX route of administration and doses did not influence on the toxicity of the combined treatment with LF. The combined therapy seems to be a safe treatment option in RA patients.

Anticuerpos antifosfolípidos en pacientes con nefritis lúpica: Estudio clínico-patológico / Antiphospholipid antibodies in lupic nephritis patients: Clinical-pathologic study

Introduction: Antiphospholipid Antibodies (APA) are detected in 30 and 40% of patients with Systemic lupus erythematosus (SLE). Antiphospholipid Syndrome nephropathy (APSN) is one of renal manifestations of APS. Histological lesions of APSN have been described in SLE. Objective: To evaluate the prevalence of APA in patients with lupus nephritis (LN), its clinical and laboratory association and the presence of APSN in renal biopsies from LN patients. Patients and Methods: We retrospectively studied 28 patients with SLE diagnosis according to ACR criteria, who underwent renal biopsies with diagnosis of LN. These patients attended to our rheumatology unit for the last 2 years. Demographic, clinical and serological data were collected at the time of the first biopsy. APA (Anticardiolipin Ig G, Ig M and lupus anticoagulant) were considered positivewhen they were positive in two opportunities during the follow up. Renal biopsies were classified according to NL classification 2004. Histological features of APSN were analyzed by 2 different pathologists who were blind to clinical data. P value <0.05 was considered statistically significant. Results: Mean age was 31 years old (17-53), 86% were female and mean SLE duration was 47 months (1-180). 54% of patients were positive for APA. There was not association between APA and first creatinine level, hypertension, amount of proteinuria and active sediment. Class II LN was most frequently associated with APA. Glomerular collapse and focal cortical atrophy (FCA) were associatedwith APA (p<0.008, p<0.005). Conclusions: APA were present in 54% of patients with LN. There was not association between APA and clinical features or histological type of LN. The main histological features of APSN were glomerular collapse and FCA