Incidence of tuberculosis among patients with rheumatoid arthritis using TNF blockers in Brazil: data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil) / Incidência de tuberculose em pacientes com artrite reumatoide em uso de bloqueadores do TNF no Brasil: dados do Registro Brasileiro de Monitoração de Terapias Biológicas BiobadaBrasil

Abstract Objectives To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. Patients and methods This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Statistical analysis: Unpaired t-test and Fisher's two-tailed test; p < 0.05. Results The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab = 676, infliximab = 547 and etanercept = 521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab = 4.43/1000 patient-years; etanercept = 1.92/1000 patient-years and infliximab = 1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. Conclusions The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.

Resumo Objetivos Avaliar incidência de tuberculose e triagem para tuberculose latente em brasileiros com artrite reumatoide em uso de agentes biológicos na prática clinica. Pacientes e métodos Estudo de coorte com dados do Registro Brasileiro de Monitoração de Terapias Biológicas (BiobadaBrasil), de 01/2009 a 05/2013, abrangeu 1.552 tratamentos, 415 somente com drogas modificadoras do curso da doença (MMCDs) sintéticas, 942 MMCDs sintéticas em associação com anti-TNF (etanercepte, infliximabe, adalimumabe) e 195 MMCDs sintéticas em associação com outros biológicos (abatacepte, rituximabe e tocilizumabe). Avaliaram-se ocorrência de tuberculose, tempo de exposição às drogas e triagem para TB. Análise estatística: teste t não pareado e teste de Fisher bicaudal; p < 0,05. Resultados O tempo de exposição dos controles foi de 981 pacientes-ano, do grupo de anti-TNF foi de 1.744 pacientes-ano (adalimumabe = 676, infliximabe = 547 e etanercepte = 521 pacientes-ano) e o de outros biológicos de 336 pacientes-ano. A incidência de TB foi de 1,01/1.000 pacientes-ano nos controles e de 2,87 pacientes-ano nos usuários de anti-TNF (adalimumabe = 4,43/1.000 pacientes-ano; etanercepte = 1,92/1.000 pacientes-ano e infliximabe = 1,82/1.000 pacientes-ano). Não houve casos de tuberculose no grupo de outros biológicos. O tempo médio de exposição até a ocorrência de tuberculose foi de 27(11) meses para o grupo anti-TNF. Conclusões A incidência de tuberculose foi maior nos usuários de MMCDs sintéticas e anti-TNF do que nos usuários de MMCDs sintéticas e de MMCDs sintéticas e biológicos não anti-TNF, e também mais tardia, sugerindo infecção durante o tratamento, e não falha na triagem.

Hepatitis C virus antibodies in high risk juvenile onset systemic lupus erythematosus / Anticorpos contra o vírus da hepatite C em pacientes de alto risco com lúpus eritematoso sistêmico de início juvenil

Abstract Objective To evaluate the prevalence of hepatitis C virus (HCV) infection in high risk juvenile systemic lupus erythematosus (JSLE). Study design Forty low income JSLE patients (6M:34F; mean age 19 ± 4.4 yrs; mean disease duration 6 ± 3.2 yrs) were studied. Twenty healthy children and adolescents matched for social economical level were included as controls. Anti-HCV tests were performed using a third generation microparticle enzyme immunoassay. Inclusion criterion was low social economical level. Results The frequencies of anti-HCV antibody were low and comparable between JSLE and control group (2.5% vs. 0, p = 1.0). JSLE patients had significantly more risk factors for HCV infection compared to the control group, including immunosuppressive treatment (90% vs. 0, p < 0.0001), hospitalization (50% vs. 12.5%, p = 0.0006) and invasive procedures (47.5% vs. 12.5%, p = 0.001). Conclusions The observed low frequency of anti-HCV antibodies in high risk JSLE suggests that this virus does not seem to have a relevant role in the pathogenesis of this disease.

Resumo Objetivo Avaliar a prevalência de infecção pelo vírus da hepatite C (VHC) em pacientes de alto risco com lúpus eritematoso sistêmico de início juvenil (LESJ). Desenho do estudo Foram estudados 40 pacientes de baixa renda com LESJ (6 H: 34 M, com média de 19 ± 4,4 anos; duração média da doença de 6 ± 3,2 anos). Incluíram-se no grupo controle 20 crianças e adolescentes saudáveis pareados por nível socioeconômico. Fizeram-se testes anti-VHC com um ensaio imunoenzimático de micropartículas de terceira geração. O critério de inclusão foi o baixo nível socioeconômico. Resultados As frequências de anticorpos anti-VHC foram baixas e comparáveis entre os grupos LESJ e controle (2,5% versus 0, p = 1). Os pacientes com LESJ tinham significativamente mais fatores de risco para infecção por VHC em comparação com o grupo controle, incluindo tratamento imunossupressor (90% versus 0, p < 0,0001), internação (50% versus 12,5%, p = 0,0006) e procedimentos invasivos (47,5% versus 12,5%, p = 0,001). Conclusões A baixa frequência de anticorpos anti-VHC observada nos pacientes de alto risco com LESJ sugere que esse vírus não parece ter um papel relevante na patogênese dessa doença.

Registro brasileiro de biológicos: processo de implementação e resultados preliminares do BiobadaBrasil / Brazilian biologic registry: BiobadaBrasil implementation process and preliminary results

OBJETIVOS: O presente estudo teve por objetivo descrever o processo de implementação de um registro nacional em um país em desenvolvimento (Brasil) e relatar os principais resultados preliminares do registro BiobadaBrasil. MATERAL E MÉTODOS: Através de um acordo com a PANLAR, o protocolo Biobadaser foi utilizado como modelo para a implementação de um novo registro no nosso país. Durante os dois primeiros anos desse esforço, o protocolo original foi adaptado, traduzido e apresentado a todos os reumatologistas brasileiros. Durante dez meses, dados de 1.037 pacientes (750 tratados com biológicos e 287 controles) de 15 centros foram coletados. RESULTADOS: A maioria dos pacientes tinha artrite reumatoide (AR) (n = 723). Infliximabe foi o agente anti-TNF mais usado, e a exposição total a biológicos foi 2.101 pacientes-ano. A razão mais comum para suspensão da droga foi ineficiência ou perda de efetividade (50 por cento), e 30 por cento dos pacientes interromperam o tratamento devido a eventos adversos. Três casos de tuberculose foram observados no grupo biológico, representando maior incidência do que aquela da população brasileira geral. Infecções foram observadas em 23 por cento dos pacientes do grupo biológico, sendo o trato respiratório superior o local mais comumente afetado. Apenas um caso de hanseníase tuberculoide foi observado. Nenhuma morte nem malignidade atribuível ao efeito dos medicamentos foi observada até fevereiro de 2010. CONCLUSÕES: A implementação do registro foi bem sucedida. Embora recente, o registro BiobadaBrasil já forneceu importantes dados.

OBJECTIVES: The present study aimed at describing the implementation process of a national registry in a developing country (Brazil) and at reporting the main preliminary results of the BiobadaBrasil registry. MATERIAL AND METHODS: Through a PANLAR agreement, the Biobadaser protocol was used as a model for implementing the new registry in our country. During the first two years of this effort, the original protocol was adapted, translated, and presented to all Brazilian rheumatologists. For ten months, data of 1,037 patients (750 subjects treated with biological drugs and 287 control subjects) from 15 centers were collected. RESULTS: Most patients had rheumatoid arthritis (RA) (n = 723). Infliximab was the most frequently used anti-TNF agent, and the total exposure to biologic drugs was 2,101 patient-years. The most common reason for interrupting drug use was lack or loss of efficacy (50 percent), while 30 percent withdrew from the treatment arm due to adverse events. Three cases of tuberculosis were observed in the biologic group, with an incidence higher than that of the general Brazilian population. Infections were observed in 23 percent of the biologic group, and the upper respiratory tract was the most commonly affected site. Only one case of tuberculoid leprosy was observed. No deaths or malignancies attributed to drug effects were observed as of February 2010. CONCLUSIONS: The implementation of the BiobadaBrasil registry was successful, and, although recent, the registry has provided important data.

Decreased high-density lipoprotein cholesterol levels in polyarticular juvenile idiopathic arthritis

OBJECTIVES: To investigate the prevalence of dyslipoproteinemia in a homogeneous cohort of polyarticular juvenile idiopathic arthritis patients. METHODS: Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis. The exclusion criteria included diabetes, thyroid dysfunction, smoking, proteinuria, lipid-lowering drugs, and hormone/diuretic therapy. Disease activity, disease duration, and therapy with corticosteroids and/or chloroquine were defined at the time of lipid measurements. RESULTS: Dyslipoproteinemia was identified in 20 of the 28 (71 percent) patients with polyarticular juvenile idiopathic arthritis. The primary lipoprotein risk factor was decreased high-density lipoprotein cholesterol (57 percent), followed by elevated levels of low-density lipoprotein cholesterol (18 percent), triglycerides (14 percent), and total cholesterol (7 percent). The male patients had decreased high-density lipoprotein cholesterol levels than the female patients (p<0.05). The incidence of decreased high-density lipoprotein cholesterol levels did not seem to be affected by disease activity or therapy because the incidence was similar in patients with active or inactive disease, with or without corticosteroid use and with or without chloroquine use. In addition, the frequency of decreased high-density lipoprotein cholesterol levels was similar in patients with short (≤5 years) vs. long (>5 years) disease duration. CONCLUSIONS: Dyslipoproteinemia is highly prevalent in patients with polyarticular juvenile idiopathic arthritis and is primarily related to decreased high-density lipoprotein cholesterol levels; therefore, early intervention is essential.