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.

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).

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.

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.

Posicionamento sobre o uso de tofacitinibe no algoritmo do Consenso 2012 da Sociedade Brasileira de Reumatologia para o tratamento da artrite reumatoide / Update on the 2012 Brazilian Society of Rheumatology Guidelines for the treatment of rheumatoid arthritis: position on the use of tofacitinib

Resumo Em 2014, o tofacitinibe, um medicamento modificador do curso da doença (MMCD) sintético, alvo-específico, inibidor seletivo das Janus quinases (JAK), foi aprovado para uso no Brasil. Este documento de posicionamento tem o objetivo de atualizar as recomendações da Sociedade Brasileira de Reumatologia (SBR) sobre o tratamento da artrite reumatoide (AR) no Brasil, especificamente com relação ao uso de MMCD sintéticos alvo-específicos. O método dessa recomendação incluiu revisão bibliográfica de artigos científicos, feita na base de dados Medline. Após a revisão, foi produzido um texto, que responde a perguntas na estrutura Pico, e considera questões de eficácia e segurança do uso do tofacitinibe para tratamento de AR em diferentes situações (como primeira linha de tratamento, após falha ao metotrexato [MTX] ou outros MMCD sintéticos convencionais, após falha da terapia biológica). Com base nas evidências existentes, e considerando os dados disponíveis sobre eficácia, segurança e custo das medicações disponíveis para tratamento da doença no Brasil, a Comissão de AR da SBR, após processo de discussão e votação de propostas, estabeleceu o seguinte posicionamento sobre o uso de tofacitinibe para o tratamento da AR no Brasil: “Tofacitinibe, em monoterapia ou em associação ao MTX, é uma opção para os pacientes com AR em atividade moderada ou alta, após falha de pelo menos dois esquemas com diferentes MMCD sintéticos e um esquema de MMCD biológico”. O grau de concordância com essa recomendação foi 7,5. Esse posicionamento poderá ser revisto nos próximos anos, com a maior experiência adquirida com o uso do medicamento.

Abstract In 2014, tofacitinib, a target-specific, synthetic disease modifying anti rheumatic drug (DMARD) and a selective inhibitor of Janus kinase (JAK) was approved for use in Brazil. This position paper aims to update the recommendations of the Brazilian Society of Rheumatology (SBR) on the treatment of rheumatoid arthritis (RA) in Brazil, specifically regarding the use of target-specific synthetic DMARDs. The method of this recommendation consisted of a literature review of scientific papers held on the Medline database. After this review, a text was produced, answering questions in Pico structure, considering efficacy and safety issues of tofacitinib use for RA treatment in different scenarios (such as first-line treatment after failure with methotrexate [MTX] or other conventional synthetic DMARDs after failure with biological therapy). Based on existing evidence, and considering the available data on efficacy, safety and cost of medications available to treat the disease in Brazil, the RA Commission of SBR, after a process of discussion and voting on proposals, established the following position on the use of tofacitinib for treatment of RA in Brazil: “Tofacitinib, alone or in combination with MTX, is an alternative for RA patients with moderate or high activity after failure of at least two different synthetic DMARDs and one biological DMARD.” The level of agreement with this recommendation was 7.5. This position may be reviewed in the coming years, in the face of a greater experience with the use of this medication.

Pulmonary involvement in rheumatoid arthritis: evaluation by radiography and spirometry.

OBJECTIVE: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA). METHODS: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry. RESULTS: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure. CONCLUSIONS: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms.

Pulmonary involvement in rheumatoid arthritis: evaluation by radiography and spirometry / Doença pulmonar em pacientes com artrite reumatoide: avaliação radiográfica e espirométrica

AbstractObjective: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA).Methods: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry.Results: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure.Conclusions: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms.

ResumoObjetivo: Determinar se métodos diagnósticos de baixa complexidade podem fornecer informações relevantes sobre doença pulmonar em pacientes com artrite reumatoide (AR).Métodos: Pacientes com AR foram selecionados aleatoriamente para um estudo transversal envolvendo avaliação clínica pulmonar, oximetria de pulso (SpO2) em repouso, radiografia de tórax e espirometria.Resultados: Um total de 246 pacientes foi submetido à avaliação completa. Metade dos pacientes na amostra relatou história de tabagismo. A proporção de pacientes com resultados anormais na espirometria, radiografia de tórax e SpO2 foi de, respectivamente, 30%, 45% e 13%. Resultados normais em radiografia de tórax, espirometria e SpO2 foram observados simultaneamente em apenas 41% dos pacientes com AR. História de tabagismo foi associada a achados espirométricos anormais, de doença pulmonar obstrutiva e de doença pulmonar restritiva, assim como radiografia de tórax anormal e com padrão intersticial. Na comparação dos pacientes com exames normais (n = 101) com aqueles com exames com alguma alteração (n = 145), houve uma diferença estatisticamente significante entre os dois grupos em relação a idade e história de tabagismo. Interessantemente, sinais de doença de vias aéreas foram observados em quase metade dos pacientes com relato de baixa exposição ao tabagismo ou de nunca ter sido fumante.Conclusões: O comprometimento pulmonar na AR pode ser identificado através de uma combinação de métodos diagnósticos simples, seguros e de baixo custo. Nossos resultados sugerem que pacientes com AR e sinais de acometimento pulmonar devem ser avaliados quanto a possíveis anormalidades pulmonares, mesmo na ausência de sintomas respiratórios.

[Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloarthritides]. / Segurança do uso de terapias biológicas para o tratamento de artrite reumatoide e espondiloartrites.

The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia/SBR) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis (RA) and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment.

Segurança do uso de terapias biológicas para o tratamento de artrite reumatoide e espondiloartrites / Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloarthritides

O tratamento das doenças reumáticas autoimunes sofreu uma progressiva melhora ao longo da última metade do século passado, que foi expandida com a contribuição das terapias biológicas ou imunobiológicos. No entanto, há que se atentar para as possibilidades de efeitos indesejáveis advindos da utilização dessa classe de medicações. A Sociedade Brasileira de Reumatologia (SBR) elaborou um documento, baseado em ampla revisão da literatura, sobre os aspectos relativos à segurança dessa classe de fármacos, mais especificamente no que diz respeito ao tratamento da artrite reumatoide (AR) e das espondiloartrites. Os temas selecionados pelos especialistas participantes, sobre os quais foram estabelecidas considerações quanto à segurança do uso de drogas biológicas, foram: ocorrência de infecções (bacterianas, virais, tuberculose), reações infusionais, reações hematológicas, neurológicas, gastrointestinais, cardiovasculares, ocorrências neoplásicas (neoplasias sólidas e da linhagem hematológica), imunogenicidade, outras ocorrências e reposta vacinal. Optou-se, por motivos didáticos, por se fazer um resumo da avaliação de segurança, de acordo com os tópicos anteriores, por classe de drogas/mecanismo de ação (antagonistas do fator de necrose tumoral, bloqueador da co-estimulação do linfócito T, depletor de linfócito B e bloqueador do receptor de interleucina-6). Em separado, foram tecidas considerações gerais sobre segurança do uso de biológicos na gravidez e na lactação. Esta revisão procura oferecer uma atualização ampla e equilibrada das experiências clínica e experimental acumuladas nas últimas duas décadas de uso de medicamentos imunobiológicos para o tratamento da AR e espondiloartrites.

The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment.

Incapacitação e qualidade de vida não são influenciadas pela prevalência de autoanticorpos em pacientes com artrite reumatoide inicial - resultados da Coorte Brasília / Disability and quality-of-life are not influenced by the prevalence of autoantibodies in early rheumatoid arthritis patients - results of the Brasília Cohort

INTRODUÇÃO: Embora muitos estudos sugiram que a presença de autoanticorpos, tais como fator reumatoide (FR) e/ou antipeptídeos citrulinados cíclicos (anti-CCP), sejam preditores de danos articulares na artrite reumatoide (AR), a associação entre os questionários de incapacidade e de qualidade de vida ainda são desconhecidos. OBJETIVOS: Avaliar a correlação entre os questionários Health Assessment Questionnaire (HAQ) e Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) com marcadores como FR, anti-CCP e antivimentina citrulinada (anti-Sa). PACIENTES E MÉTODOS: Foram avaliados no momento do diagnóstico 65 pacientes da Coorte Brasília com AR inicial. Foram realizadas sorologias (ELISA) para FR (IgM, IgG e IgA), anti-CCP (CCP2, CCP3 e CCP3.1) e anti-Sa, com a aplicação do HAQ e SF-36 na avaliação inicial. RESULTADOS: A idade média foi de 45 anos, predominando o gênero feminino (86%). Na avaliação inicial, o FR foi positivo em 32 indivíduos (49,23%); anti-CCP em 34 indivíduos (52,3%); e anti-Sa em nove indivíduos (13,8%). O escore inicial do HAQ foi de 1,8. Os escores dos domínios do SF-36 foram: emocional, 19,3; social, 43,1; dor, 25,43; estado geral, 57,6; saúde mental, 48,1; vitalidade, 49,5; físico, 4,6; e limitação por aspecto físico, 24,7. HAQ e escores do SF-36 não variaram com os níveis de autoanticorpos. CONCLUSÃO: Muitos pacientes com AR inicial apresentam comprometimento na qualidade de vida relacionada aos domínios da capacidade física e mental. Embora FR e anti-CCP tenham sido relacionados com dano articular e pior prognóstico clínico, não há correlação entre os questionários e as avaliações da qualidade de vida e incapacidade.

INTRODUCTION: Although many studies have suggested that the presence of autoantibodies, such as rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) in rheumatoid arthritis (RA) are predictors of joint damage, the association with disability and quality of life questionnaires are not known. OBJECTIVES: To evaluate the correlation between the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) scores with serological markers, such as RF, anti-CCP, and anti-citrullinated vimentin (anti-Sa). PATIENTS AND METHODS: Sixty five patients with early RA (ERA) from the Brasília Cohort of ERA were evaluated. Serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1), and anti-Sa were performed, with the application of the HAQ and SF-36 questionnaires in the initial evaluation. RESULTS: The mean age was 45 years, with a female predominance (86%). At the initial evaluation, RF was positive in 32 individuals (49.23%), anti-CCP in 34 (52.3%), and anti-Sa in nine (13.8%). The initial HAQ score was 1.8. The SF-36 scores were as follow: role-emotional, 19.3; social functioning, 43.1; bodily pain, 25.43; general health, 57.6; mental health, 48.1; vitality, 49.5; role-physical, 4.6; and physical functioning, 24.7. The HAQ and SF-36 scores did not vary with autoantibody levels. CONCLUSION: In many patients, ERA has a major impact on physical ability and health-related quality of life. Although RF and anti-CCP tests have been related with joint destruction and worse clinical prognosis, there is no correlation with the results of questionnaires of quality of life and disability.

Diagnóstico por imagem da artrite reumatoide inicial / Imaging diagnosis of early rheumatoid arthritis

O diagnóstico precoce da artrite reumatoide é essencial para o manejo adequado da condição. Atualmente, considera-se que a fase inicial da doença constitui uma janela de oportunidade terapêutica para a artrite reumatoide. Embora o diagnóstico seja primordialmente clínico, o desenvolvimento e o aprimoramento de métodos laboratoriais e de imagem têm contribuído para o diagnóstico mais precoce e a determinação da conduta na artrite reumatoide inicial. Neste artigo os autores revisam o papel dos principais métodos de imagem utilizados para a avaliação da artrite reumatoide inicial, notadamente a radiologia convencional, a ultrassonografia e a ressonância magnética.

Early diagnosis of rheumatoid arthritis is essential for its proper management. Currently, the initial phase of rheumatoid arthritis is known to provide a window of therapeutic opportunity. Although the diagnosis is primarily clinical, the development and improvement of laboratory and imaging methods have contributed to earlier diagnosis and determination of procedures in early rheumatoid arthritis. In this article, the authors review the role of the major imaging methods used for assessing early rheumatoid arthritis, especially conventional radiography, ultrasonography, and magnetic resonance imaging.

TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients.

OBJECTIVE: To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in RA and spondyloarthritis (SpA) patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls. METHODS: One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. RESULTS: After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. CONCLUSION: This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01151644.

Autoanticorpos na artrite reumatoide inicial: coorte Brasília - resultados de uma análise seriada de três anos / Autoantibodies in early rheumatoid arthritis: Brasília cohort - results of a three-year serial analysis

O valor diagnóstico e prognóstico da análise seriada dos anticorpos como fator reumatoide (FR), anticorpos antipeptídeos citrulinados cíclicos (anti-CCP) e antivimentina citrulinada (anti-Sa) não está definido nos pacientes com artrite reumatoide inicial (ERA). OBJETIVOS: Avaliar de forma prospectiva a presença de FR, anti-CCP e anti-Sa em pacientes com ERA. PACIENTES E MÉTODOS: Quarenta pacientes da coorte Brasília de ERA (menos de 12 meses) foram avaliados e monitorados durante três anos. Os dados clínicos e demográficos foram registrados, além dos resultados (ELISA) para FR (IgM, IgG e IgA), anti-CCP (CCP2, CCP3 e CCP3.1) e anti-Sa na avaliação inicial e aos 3, 6, 12, 18, 24 e 36 meses de acompanhamento. Comparações pelos testes t de Student e t pareado. RESULTADOS: A idade média foi de 45 anos, 90% dos pacientes do gênero feminino. No momento do diagnóstico, FR foi observado em 50% dos casos (FR IgA 42%, FR IgG 30% e FR IgM 50%), anti-CCP em 52,5% (não houve diferença entre CCP2, CCP3 e CCP3.1) e anti-Sa em 10%. Após três anos, não houve diferença na prevalência de FR e anti-CCP, mas a de anti-Sa aumentou para 17,5% (P = 0,001). CONCLUSÃO: A análise repetida do FR e anti-CCP, incluindo aqui diferentes isotipos, durante três anos de acompanhamento, não mostrou mudanças significativas. A terceira geração do anti-CCP não aumentou o valor diagnóstico dos testes de segunda geração.

The diagnostic and prognostic value of the serial measurement of antibodies, such as rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and anti-citrullinated vimentin (anti-Sa) antibodies, has not been defined in early rheumatoid arthritis (ERA). OBJECTIVES: To prospectively assess the presence of RF, anti-CCP, and anti-Sa in ERA patients. PATIENTS AND METHODS: Forty ERA (less than 12 months) patients of the Brasília cohort were evaluated and followed up for three years. Both clinical and demographic data were recorded, in addition to the results (ELISA) of RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1), and anti-Sa at the baseline assessment and after 3, 6, 12, 18, 24 and 36 months of follow-up. The results were compared by use of Student t test and paired t test. RESULTS: The patients' mean age was 45 years, and 90% of them were female. At the time of diagnosis, RF was identified in 50% of the patients (RF IgA, 42%; RF IgG, 30%; and RF IgM, 50%), anti-CCP in 52.5% (no difference between CCP2, CCP3, and CCP3.1), and anti-Sa in 10%. After three years, no difference was observed in RF and anti-CCP prevalence, but anti-Sa increased to 17.5% (P = 0.001). CONCLUSION: Repeated RF and anti-CCP measurement, including different isotypes, during three years of follow-up showed no significant changes. The third generation of anti-CCP assays did not increase the diagnostic value of the second-generation assays.

Ultrasound findings in infantile systemic hyalinosis.

To describe clinical and ultrasound findings in a patient with infantile systemic hyalinosis (ISH). A 5-month-old boy was evaluated of joint contractures. In addition to clinical and laboratory investigations, an ultrasound of his joints was done and compared to a child with similar age. On examination, a short neck, gingival hyperplasia and papular rash were noted. Joint examination showed painful passive movement, reduced range of motion, and joint contractures in knees, elbows, and small joints of the hands, without any evidence of synovial thickness. Ultrasound of the affected joints showed irregular cortical surface of MCPs and PIP, the presence of osteophytes and bone erosions, increased synovial fluid without evidence of synovial hyperplasia. This is the first report to show evidence of US findings in ISH. Ultrasound findings may help to distinguish ISH from JIA in early stages.

Central diabetes insipidus induced by tuberculosis in a rheumatoid arthritis patient.

Tuberculosis, a polymorphic disease, is a diagnostic challenge, particularly when arises concomitantly to an autoimmune disease such as rheumatoid arthritis (RA). Herein, the authors describe a 33-year-old woman with nodular RA who was being treated with methotrexate, sulfasalazine and corticosteroids and presented with subcutaneous nodules simultaneously with aseptic meningitis. Mycobacterium tuberculosis was identified in cultures from a biopsy of an axillary nodule. The patient also developed polyuria and polydipsia with normal glycemia; antidiuretic hormone (ADH) treatment before and after a 3% saline infusion test was performed and diabetes insipidus was diagnosed. An encephalic MRI showed sellar and suprasellar masses, suggesting central diabetes insipidus (CDI). The patient received standard tuberculosis (TB) treatment for 6 months and also DDAVP (desmopressin acetate) during this period. Control of CDI was observed. A pre-surgical magnetic resonance imaging (MRI) showed no pituitary mass. It is known that intrasellar tuberculoma occurs in only 1% of TB patients. TB should be considered in the differential diagnosis of CDI, especially in immunosupressed patients and in countries where this infection is a serious public health problem.

Características laboratoriais de um grupo de pacientes com artrite reumatoide inicial / Laboratory characteristics of a cohort of patients with early rheumatoid arthritis

INTRODUÇÃO/OBJETIVO: Caracterizar uma população de pacientes com artrite reumatoide (AR) inicial quanto aos aspectos laboratoriais, comparando-a com outras coortes similares. PACIENTES E MÉTODOS: Os dados apresentados fazem parte de um estudo prospectivo de coorte incidente, em que foram avaliados 65 pacientes com AR inicial, acompanhados por 36 meses a partir do diagnóstico, na Clínica de Artrite Reumatoide Inicial do Hospital Universitário de Brasília (HUB). Foram registrados os dados demográficos, clínicos e laboratoriais pertinentes à avaliação inicial da coorte, incluindo hematimetria, provas de atividade inflamatória e presença de autoanticorpos (fator reumatoide - FR, anticorpos antipeptídeos citrulinados cíclicos - anti-CCP e antivimentina citrulinada - anti-Sa). RESULTADOS: Houve predomínio de mulheres (86 por cento), com média de idade de 45,6 anos. Doze pacientes (18,46 por cento) tiveram o diagnóstico laboratorial de anemia (hemoglobina < 12 g/dL). Velocidade de hemossedimentação (VHS) e proteína C reativa (PCR) encontravam-se acima do valor de referência em 51 (78,46 por cento) e 46 (70,76 por cento) pacientes, respectivamente. Trinta e dois indivíduos (49,23 por cento) foram positivos para pelo menos um dos isotipos de FR, sendo que 28 pacientes (43,07 por cento) foram positivos para FR IgA, 19 (29,23 por cento) para FR IgG e 32 (49,23 por cento) para FR IgM, respectivamente; 34 pacientes (52,30 por cento do total) foram positivos para pelo menos uma das técnicas utilizadas na averiguação de anti-CCP (CCP2, CCP3 ou CCP3.1), enquanto 9 (13,85 por cento) o foram para anti-Sa. CONCLUSÕES: As características laboratoriais dos pacientes acompanhados nessa coorte brasileira se assemelham em vários aspectos a coortes norte-americanas, europeias e latino-americanas anteriormente publicadas.

INTRODUCTION/OBJECTIVE: To characterize a population of patients with early rheumatoid arthritis (RA) according to laboratory aspects, comparing it with other similar cohorts. METHODS: Data presented are part of a prospective incident cohort study that evaluated 65 patients with early RA, followed for 36 months from the diagnosis at Early Rheumatoid Arthritis Clinic of Hospital Universitário de Brasília (HUB). We recorded demographics, clinical, and laboratory data relevant to the cohort initial assessment, including red blood cells, evidence of inflammatory activity, and presence of autoantibodies (rheumatoid factor (RF)), cyclic citrullinated peptide antibodies (anti-CCP), and antivimentin citrullinated (anti-Sa). RESULTS: There was a preponderance of female (86 percent) with mean age of 45.6 years. Twelve patients (18.46 percent) had laboratory diagnosis of anemia (hemoglobin < 12 g / dL). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were above the reference value for 51 (78.46 percent) and 46 (70.76 percent) patients, respectively. Thirty-two patients (49.23 percent) were positive for at least one of the RF isotypes, and 28 patients (43.07 percent) were positive for IgA RF, 19 (29.23 percent) for IgG, and 32 ( 49.23 percent) for IgM RF, respectively; 34 patients (52.30 percent) were positive for at least one of the techniques used in investigation of anti-CCP (CCP2, or CCP3, or CCP3.1), while 9 (13,85 percent) were positive for anti-Sa. CONCLUSIONS: The laboratory characteristics of patients enrolled in this Brazilian cohort are similar in many respects to those of North-American, European, and Latin-American cohorts previously published.

Avaliação prospectiva da qualidade de vida em uma coorte de pacientes com artrite reumatoide inicial / Prospective evaluation of the quality of life in a cohort of patients with early rheumatoid arthritis

INTRODUÇÃO: Poucos estudos avaliaram, de forma prospectiva, os instrumentos de aferição de qualidade de vida, tanto genéricos quanto específicos, em pacientes com artrite reumatoide (AR) inicial. OBJETIVO: O objetivo deste trabalho foi caracterizar uma população de pacientes com AR inicial (menos de 12 meses de sintomas da doença no momento do diagnóstico) acompanhada prospectivamente quanto ao padrão de respostas aos questionários de qualidade de vida Health Assessment Questionnaire (HAQ) e o Medical Outcomes Study SF-36 Health Survey (SF - 36). PACIENTES E MÉTODOS: Foram avaliados 40 pacientes com diagnóstico de AR inicial no momento do diagnóstico, acompanhados prospectivamente por três anos, em uso de esquema terapêutico padronizado. Registrados os dados demográficos e clínicos e aplicados os questionários HAQ e SF-36 na avaliação inicial e aos 3, 6, 12, 18, 24 e 36 meses de acompanhamento. Comparações feitas pelo teste t de Student, t pareado e Wilcoxon (nível de significância de 5 por cento). RESULTADOS: A idade média foi de 45 anos e predominou o sexo feminino (90 por cento). A média do escore do HAQ inicial foi 1,89, com declínio progressivo até 0,77 no terceiro ano (P < 0,0001). A maioria dos elementos do SF-36 apresentaram significativa melhora durante os três anos de seguimento, com exceção de estado geral e vitalidade. CONCLUSÃO: Nessa população de pacientes com AR inicial no momento do diagnóstico, observou-se alterações importantes impacto na qualidade de vida no momento do diagnóstico, conforme avaliado pelos questionários HAQ e SF-36. O tratamento precoce da AR parece se associar à melhora da qualidade de vida relacionada com a saúde relatada pelo paciente.

INTRODUCTION: Few studies have prospectively assessed the tools used to measure quality of life, both generic and specific, in patients with early rheumatoid arthritis (RA). OBJECTIVE: The objective of this study was to characterize a population of patients with early RA (less than 12 months after symptom onset at the time of the diagnosis) prospectively followed for the pattern of responses to questionnaires addressing quality of life, the Health Assessment Questionnaire (HAQ) and Medical Outcomes Study SF-36 Health Survey (SF-36). PATIENTS AND METHODS: Forty patients with early RA at the time of diagnosis, treated with a standard treatment regimen, were prospectively followed for 3 years. Demographic and clinical data were recorded, and HAQ and SF-36 questionnaires were applied at baseline and after 3, 6, 12, 18, 24, and 36 months. Paired Student t test and Wilcoxon test were used for comparisons (significance level of 5 percent). RESULTS: The mean age was 45 years, with a prevalence of the female gender (90 percent). The average score of the initial HAQ was 1.89, with a progressive decline to 0.77 in the third year (P < 0.0001). Most domains of the SF-36 questionnaire presented significant improvement during the three years of follow-up, except for general health and vitality. CONCLUSION: In this population of patients with early RA at the time of diagnosis, the results showed significant impact on quality of life at the time of diagnosis, as measured by HAQ and SF-36 questionnaires. The early treatment of RA seems to be associated with improved health-related quality of life reported by patients.

Características demográficas e clínicas de uma coorte de pacientes com artrite reumatoide inicial / Demographic and clinical characteristics of a cohort of patients with early rheumatoid arthritis

INTRODUÇÃO: Há poucos estudos realizados com populações latino-americanas sobre as características demográficas e clínicas dos pacientes com diagnóstico de artrite reumatoide (AR) inicial. OBJETIVO: Caracterizar uma população de pacientes com AR inicial acompanhada, prospectivamente, quanto aos aspectos demográficos e clínicos, comparando-a com outras coortes similares. PACIENTES E MÉTODOS: Os dados apresentados fazem parte de um estudo prospectivo de coorte incidente, em que foram avaliados 65 pacientes com AR inicial, acompanhados de forma regular por 36 meses a partir do diagnóstico na Clínica de Artrite Reumatoide Inicial do Hospital Universitário de Brasília (HUB). Foram registrados os dados demográficos e clínicos pertinentes à avaliação inicial da coorte, incluindo características gerais, dados da história clínica e exame físico. Empregou-se estatística descritiva das variáveis analisadas. RESULTADOS: Houve predomínio de mulheres (86 por cento), com média de idade de 45,6 anos, brancas ou pardas (47,6 por cento), pertencentes à classe social média-baixa (53,85 por cento), com 8,3 anos de escolaridade em média. A maior parte dos pacientes iniciou os sintomas de forma aguda (76,9 por cento), com acometimento poliarticular (69,2 por cento), sinovite persistente em mãos (90,7 por cento) e rigidez matinal prolongada (157 minutos, em média). Os pacientes apresentaram uma contagem média de articulações dolorosas (18,6) e edemaciadas (13,9) elevada e alta prevalência de nódulos reumatoides (15,3 por cento), o que sugere doença de apresentação agressiva em sua fase inicial. CONCLUSÃO: As características demográficas e clínicas dos pacientes acompanhados nessa coorte brasileira divergiram em vários aspectos das coortes norte-americanas, europeias e latinoamericanas anteriormente publicadas.

INTRODUCTION: Very few studies carried out with Latin American populations on the demographic and clinical characteristics of patients diagnosed with early rheumatoid arthritis (RA) can be found in the literature. OBJECTIVE: To characterize a population of patients with early RA, prospectively followed, concerning demographic and clinical aspects and compare them with other similar cohorts. PATIENTS AND METHODS: The data presented are part of an incident cohort prospective study, in which 65 patients with early RA were evaluated and followed regularly for 36 months at the Early Rheumatoid Arthritis Outpatient Clinic of the University Hospital of Brasília (HUB, from the Portuguese). The demographic and clinical data of the initial evaluation, including general characteristics, clinical history, and physical examination were recorded. Descriptive statistics of the variables was applied. RESULTS: Women (86 percent) with a mean age of 45.6 years, Caucasian or Black (47.6 percent), belonging to intermediate-low social classes (53.85 percent), with 8.3 years of schooling, predominated. The presenting symptoms of the majority of patients were acute (76.9 percent), with polyarticular onset (69.2 percent), persistent synovitis of the hands (90.7 percent), and prolonged morning stiffness (157 minutes on average). Patients had a high average score of painful (18.6) and swollen (13.9) joints and high prevalence of rheumatoid nodules (15.3 percent), which suggests disease with aggressive presentation in its initial phases. CONCLUSION: The demographic and clinical characteristics of patients enrolled in this Brazilian cohort differed, on several aspects, from previously published North American, European, and Latin American cohorts.

Princípios gerais do tratamento da artrite reumatoide inicial: [revisão] / General principles for treatment of early rheumatoid arthritis: [review]

Os principais objetivos do tratamento de um paciente com artrite reumatóide (AR) são: reduzir a dor, o edema articular e os sintomas constitucionais, como a fadiga, melhorar a função articular, interromper a progressão do dano ósseo-cartilaginoso, prevenir incapacidades e reduzir a morbimortalidade. Nos últimos anos, o conceito terapêutico da AR inicial (primeiros 12 meses de sintomas da doença) sofreu grandes mudanças. Três aspectos, em particular, passaram a ser base do novo paradigma de tratamento: a precocidade do diagnóstico, o início imediato das drogas modificadoras do curso da doença (DMARD) e o controle rigoroso da atividade inflamatória. Nesse artigo, os autores fazem uma revisão dos princípios gerais do manejo de pacientes com diagnóstico de AR inicial.

The main goals of the treatment of a patient with RA are: to reduce pain, joint swelling and constitutional symptoms such as fatigue, to improve joint function, stop progression of bone-cartilage damage , prevent disabilities and reduce morbidity and mortality. In recent years, the therapeutic concept of early RA (first 12 months of symptoms) has undergone major changes. Three aspects in particular have become the basis of the new treatment paradigm: early diagnosis, immediate beginning of Disease Modifying Antirheumatic Drugs therapy (DMARD) and strict control of the inflammatory activity. In this article, the authors review the general principles of management of patients with early RA.

Artrite reumatoide inicial: conceitos / Early rheumatoid arthritis: concepts

A generalização do conceito de artrite reumatoide - AR inicial e da existência de uma janela de oportunidade terapêutica - período de tempo no qual a instituição de terapia adequada para a doença determinaria melhora clínica - firmaram a noção de que diagnóstico e tratamento precoces modificam o curso da doença. Atualmente, almeja-se avaliar um paciente com sintomas articulares na primeira oportunidade possível e a definição da fase inicial da AR compreende as primeiras semanas ou meses de sintomas (em geral, menos de 12 meses), destacando-se como período crítico as primeiras 12 semanas de manifestações como a AR muito inicial ou muito precoce. Embora todos os pacientes necessitem de avaliação e tratamento precoces, há razões específicas pelas quais é necessário o pronto envolvimento do especialista na avaliação de pacientes com diagnóstico de AR precoce, uma vez que a inflamação que caracteriza a doença deve ser suprimida o mais rápido possível. Não diagnosticar ou não tratar de forma adequada um paciente com AR em fase bem inicial da doença aumenta o risco de evolução com inflamação persistente e dano articular progressivo. Por outro lado, tratar agressivamente pacientes com artrite leve, que provavelmente não progredirão para formas erosivas é igualmente danoso - expõe o paciente a riscos sem benefício comprovado e representa o oposto do tratamento precoce efetivo. Portanto, dentro do conceito atual de janela de oportunidade, é essencial fazer o diagnóstico precoce da AR e estabelecer o mais rapidamente possível quais pacientes evoluirão para formas mais graves, e, portanto, necessitarão de terapia mais agressiva.

Generalization of the concept of early rheumatoid arthritis -RA and existence of a window of therapeutic opportunity, the period when appropriate therapy for this disease would determine clinical improvement, led to the concept that early diagnosis and treatment can change the disease's course. Currently, the goal is to evaluate patients with joint symptoms at the earliest opportunity. Definition of the initial phase of RA includes the first few weeks or months of symptoms (usually less than 12 months), and the first 12 weeks of symptoms of very early or initial RA are considered to be the critical period. Although all patients require early assessment and treatment, there are specific reasons for the involvement of a specialist soon in the evaluation of patients with early RA, since the inflammation that characterizes the disease should be treated as soon as possible. Failure to diagnose or treat a patient with RA at the very early stage of the disease increases the risk of progression to persistent joint inflammation and damage. On the other hand, aggressively treating patients with mild arthritis, which probably will not evolve to erosive forms is equally damaging. It exposes patients to risk without proven benefits and represents the opposite of effective early treatment. Therefore, within the current concept of a window of opportunity, early diagnosis of RA is essential and to establish, as soon as possible those patients who will progress to more severe forms, and therefore require more aggressive therapy.