Discordance between the patient's and physician's global assessment in rheumatoid arthritis: Data from the REAL study-Brazil.

BACKGROUND: Discordance between patient's global assessment (PtGA) and physician's global assessment (PhGA) has been described in rheumatoid arthritis (RA). Understanding the reasons for this discrepancy is important in the context of treat-to-target treatment strategy. OBJECTIVE: To assess the determinants of PtGA and PhGA and factors associated with discordance between them. METHODS: The REAL study included RA patients from Brazilian public health centers. Clinical, laboratory and outcomes measures were collected. PtGA and the PhGA were rated on a visual analog scale and analyzed. Three groups were defined: no discordance (difference between PtGA and PhGA within 3 cm), positive discordance (PtGA exceeding PhGA by >3 cm), and negative discordance (PtGA less than PhGA by >3 cm). Multivariate regression analysis was used to identify determinants of PtGA and PhGA and their discordance. RESULTS: 1115 patients (89,4% female, mean age 56.7y and median disease duration of 12.7y) were enrolled. Two factors were associated with PtGA in the final multivariate model: one point increase in the pain scale leads to an increase of 0.62 in PtGA; one point increase in HAQ increases by 9,25 points the PtGA. The factors associated with PhGA were pain scale, number of tender and swollen joints (NTJ and NSJ), positive RF, ESR, HAQ-DI and use of corticosteroids. Discordance between patient and physician was found in 30.52%: positive discordance in 24.6% and negative discordance in 5.92%. An increase of one point in the NSJ was associated with a 12% increase in the chance of negative discordance. The chance of positive discordance increased by 90% and 2% for each unit increased in HAQ-DI and pain scale respectively. Finally, the chance of positive discordance decreased by 3% for each point increased in NTJ and by 15% for each point increased in NSJ. CONCLUSION: In one-third of the assessments, there was disagreement between PtGA and PhGA (a positive discordance was found in 80% of them). Pain and function were determinants for patients to estimate disease activity, while swollen joints was the main factor related to a worse physician's evaluation. These data show how different can be the perspectives of patients and assistants.

Correction: Causes of synthetic disease-modifying drug discontinuation in rheumatoid arthritis: Data from a large real-life cohort.

[This corrects the article DOI: 10.1371/journal.pone.0213219.].

Causes of synthetic disease-modifying drug discontinuation in rheumatoid arthritis: Data from a large real-life cohort.

The treatment of rheumatoid arthritis (RA) has evolved rapidly in recent years. Nonetheless, conventional synthetic disease-modifying drugs (csDMARDs) remain the gold standard for RA treatment. The treatment for RA is expensive and this has a negative impact on public health. Given the low cost of csDMARDs compared to those of other treatment strategies, it is important to manage this type of treatment properly. Information on the duration of use of each drug and the reasons for their discontinuation is relevant to medical practitioners as it could improve the information available regarding side effects and their proper management. Moreover, data from clinical practice in the population can provide health care managers with information for resource allocation and optimization of csDMARD use with a consequent cost reduction in the treatment of RA. In this cross-sectional study, we aimed to describe the use of csDMARDs in public health services in Brazil, emphasizing on the duration of use and reasons for discontinuation of each drug. This study is a part of the REAL, a multicenter project that evaluated Brazilian patients with RA from eleven rheumatology services from August to October 2015. Patients were examined clinically, and an analysis of complementary exams and medical records was performed. A total of 1125 patients were included. 98.5% were women with a median age of 55.6 years. 36% and 90.84% patients were using biological disease-modifying drugs (bDMARDs) and csDMARDs, respectively. The duration of use and doses of each medication and the causes of suspension were analyzed. Most of the patients analyzed in this study were using csDMARDs for prolonged periods and methotrexate showed the longest duration of use. Interruption indexes due to ineffectiveness and side effects were analyzed. The knowledge of common adverse effects may alert attending physicians to the proper management of effective and low-cost therapeutic groups.

Leptin as an obesity marker in rheumatoid arthritis.

The determination of excess of body fat mass provides a more suitable determinant of obesity in rheumatoid arthritis patients; however, body mass index (BMI) may not be accurate for the quantification of adiposity. To identify a marker of excess adiposity in women with rheumatoid arthritis (RA) using different methods for fat mass evaluation. A cross-sectional study was conducted in adult female patients with RA. Disease activity was assessed by DAS28-ESR, and obesity was determined by waist circumference (WC), BMI and dual-energy X-ray absorptiometry (DXA). The Human Bone Metabolism kit (Merck Millipore, Darmstadt, Alemanha) was used to determine the plasma levels of leptin, TNF-α, IL-6, and IL-1ß by quantification of serum proteins by technical microspheres (LUMINEX, TX, USA). Adiponectin was measured by enzyme-linked immunosorbent assay sandwich kit (R&D Systems, Minneapolis, MN, USA). Eighty-nine female patients, median age of 55.4 (± 11.6) years, and median disease duration of 16.4 (± 14.9) years were included. The frequency of obesity was 33.7% according to BMI, 89.9% with WC, and 56.1% with DXA. The median serum leptin concentration was the only marker that correlated with body fat percentage according to the three methods. This correlation was positive and not influenced by DAS28, C-reactive protein, erythrocyte sedimentation rate, or inflammatory cytokines levels (IL-6, TNF-α, IL-1ß). Analysis of ROC curves determined the cut-off point of 10.3 ng/mL of leptin as an obesity marker, with a sensitivity of 96.43% and a specificity of 23.81%. Serum leptin correlates positively with fat mass and is potentially useful in excess fat mass determination in clinical practice.

Which is the best cutoff of body mass index to identify obesity in female patients with rheumatoid arthritis? A study using dual energy X-ray absorptiometry body composition / Qual o melhor ponto de corte de índice de massa corporal para diagnosticar a obesidade em mulheres com artrite reumatoide? Um estudo que usa a composição corporal pela absorciometria com raios X de dupla energia

ABSTRACT Introduction: Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. Objective: To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy X-ray absorptiometry (DXA)-based obesity criterion. Patients and method: Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. Results: Eighty two patients were included, mean age 55 ± 10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value ≥ 25 kg/m2 was the best for definition of obesity in female patients with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of sensitivity and 35% of specificity, the best value to detect obesity was 86 cm. Conclusion: A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25 kg/m2 and WC cutoff point of 86 cm were the most appropriate to detect obesity.

RESUMO Introdução: Medidas antropométricas universalmente usadas para diagnosticar obesidade na população geral podem não apresentar a mesma performance em pacientes com artrite reumatoide. Objetivos: Determinar pontos de corte do índice de massa corporal (IMC) e da circunferência de cintura (CC) para detecção de obesidade em mulheres com artrite reumatoide (AR) por meio da comparação dessas medidas antropométricas habituais com os índices de adiposidade obtidos pela densitometria óssea por dupla emissão de raios X (DXA). Pacientes e método: Mulheres adultas com mais de seis meses de diagnóstico de AR foram submetidas a avaliação clínica com medidas antropométricas e à DXA com exame da composição corporal. Resultados: Foram incluídas 82 pacientes, média de 55± 10,7 anos. O diagnóstico de obesidade na amostra foi de 31,7% pelo IMC, 86,6% pela circunferência de cintura e 59,8% pela DXA. Considerando a DXA o padrão-ouro, o valor de IMC acima de 25 kg/m2 foi o mais adequado para definição de obesidade nas pacientes com AR, apresentou sensibilidade de 80% e especificidade de 60%. Da mesma forma, para a CC, com 80% de sensibilidade e de 35% de especificidade, o valor encontrado foi de 86 cm para se detectar a obesidade. Conclusão: Foi elevado o porcentual de pacientes obesas. Os pontos de corte tradicionalmente usados para obesidade não foram adequados para nossa amostra. Para essa população de pacientes femininas com diagnóstico de AR, o ponto de corte de 25 kg/m2 para IMC e de 86 cm para CC foi o mais adequado para definir obesidade.

Which is the best cutoff of body mass index to identify obesity in female patients with rheumatoid arthritis? A study using dual energy X-ray absorptiometry body composition.

INTRODUCTION: Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. OBJECTIVE: To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy X-ray absorptiometry (DXA)-based obesity criterion. PATIENTS AND METHOD: Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. RESULTS: Eighty two patients were included, mean age 55±10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value≥25kg/m2 was the best for definition of obesity in female patients with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of sensitivity and 35% of specificity, the best value to detect obesity was 86cm. CONCLUSION: A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25kg/m2 and WC cutoff point of 86cm were the most appropriate to detect obesity.

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.

Update on the 2012 Brazilian Society of Rheumatology Guidelines for the treatment of rheumatoid arthritis: position on the use of tofacitinib.

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.

Prevalence of serological markers for celiac disease (IgA and IgG class antigliadin antibodies and IgA class antiendomysium antibodies) in patients with autoimmune rheumatologic diseases in Belo Horizonte, MG, Brazil.

CONTEXT: Patients with autoimmune rheumatologic conditions and celiac disease tend to have a variety of autoantibodies, many of which have no clear pathogenic role. The literature contains frequent reports of celiac disease being more prevalent in patients with rheumatologic diseases, although this remains controversial. OBJECTIVES: To investigate the prevalence of positive serum tests for celiac disease, particularly IgA and IgG antigliadin (AGA) antibodies and IgA antiendomysium antibodies (EmA) in patients with autoimmune rheumatologic diseases. A second aim was to correlate positive serum tests with prednisone and immunosuppressant medication. METHODS: A total of 190 adults and pediatric patients with a variety of autoimmune rheumatologic diseases (systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis and spondyloarthrophathies) were evaluated and tested for IgA and IgG antigliadin-antibodies and IgA antiendomysium antibodies. Patients with positive serum tests underwent endoscopic duodenal biopsies for pathology studies. RESULTS: There were four positive sera (2.1%) for AGA IgA, all of which tested negative for AGA IgG and EmA. Three sera (1.6%) tested positive for AGA IgG; all were negative for AGA IgA and EmA. The EmA test at a 1:2.5 serum dilution tested positive in 94 patients (49.5%); at a 1:5 serum dilution it was positive in 41 patients (21.6%). Eleven subjects tested positive for EmA at 1:40 dilution; and all of these tested negative for IgA tissue antitransglutaminase (tTG) antibodies. Nine of the 11 EmA-positive patients and all 7 patients with positive antigliadin antibodies tests underwent duodenal endoscopic biopsies, and no significant changes were demonstrated in their duodenal mucosa. A positive EmA was associated with elevated optical density AGA IgA readings; however, there was no relationship between positive EmA and AGA IgG optical density readings. Prednisone and immunosuppressant use were unrelated to AGA IgA optical density readings or AGA IgG readings. These drugs were associated with fewer positive EmA tests. CONCLUSIONS: Positive AGAA, AGAG or EmA results are probably nonspecific for the presence of celiac disease among autoimmune rheumatologic disease patients. The intake of prednisone and immunosuprressant drugs seems to reduce the prevalence of IgA EmA, but it does not interfere with antigliadin antibodies tests.Further studies are required to estimate more accurately the prevalence of this disease in rheumatologic patients.

Prevalence of serological markers for celiac disease (IgA and IgG class antigliadin antibodies and IgA class antiendomysium antibodies) in patients with autoimmune rheumatologic diseases in Belo Horizonte, MG, Brazil / Pesquisa de anticorpos antigliadina (classes IgA e IgG) e anticorpos antiendomísio classe IgA, em pacientes com doenças reumatológicas autoimunes em Belo Horizonte, Brasil

CONTEXT: Patients with autoimmune rheumatologic conditions and celiac disease tend to have a variety of autoantibodies, many of which have no clear pathogenic role. The literature contains frequent reports of celiac disease being more prevalent in patients with rheumatologic diseases, although this remains controversial. OBJECTIVES: To investigate the prevalence of positive serum tests for celiac disease, particularly IgA and IgG antigliadin (AGA) antibodies and IgA antiendomysium antibodies (EmA) in patients with autoimmune rheumatologic diseases. A second aim was to correlate positive serum tests with prednisone and immunosuppressant medication. METHODS: A total of 190 adults and pediatric patients with a variety of autoimmune rheumatologic diseases (systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis and spondyloarthrophathies) were evaluated and tested for IgA and IgG antigliadin-antibodies and IgA antiendomysium antibodies. Patients with positive serum tests underwent endoscopic duodenal biopsies for pathology studies. RESULTS: There were four positive sera (2.1 percent) for AGA IgA, all of which tested negative for AGA IgG and EmA. Three sera (1.6 percent) tested positive for AGA IgG; all were negative for AGA IgA and EmA. The EmA test at a 1:2.5 serum dilution tested positive in 94 patients (49.5 percent); at a 1:5 serum dilution it was positive in 41 patients (21.6 percent). Eleven subjects tested positive for EmA at 1:40 dilution; and all of these tested negative for IgA tissue antitransglutaminase (tTG) antibodies. Nine of the 11 EmA-positive patients and all 7 patients with positive antigliadin antibodies tests underwent duodenal endoscopic biopsies, and no significant changes were demonstrated in their duodenal mucosa. A positive EmA was associated with elevated optical density AGA IgA readings; however, there was no relationship between positive EmA and AGA IgG optical density readings. Prednisone and immunosuppressant use were unrelated to AGA IgA optical density readings or AGA IgG readings. These drugs were associated with fewer positive EmA tests. CONCLUSIONS: Positive AGAA, AGAG or EmA results are probably nonspecific for the presence of celiac disease among autoimmune rheumatologic disease patients. The intake of prednisone and immunosuprressant drugs seems to reduce the prevalence of IgA EmA, but it does not interfere with antigliadin antibodies tests.Further studies are required to estimate more accurately the prevalence of this disease in rheumatologic patients.

CONTEXTO: Tanto os pacientes com doenças reumatológicas autoimunes quanto os com doença celíaca costumam apresentar vários tipos de autoanticorpos, muitos deles ainda sem papel definido na etiopatogênese dessas afecções. Apesar de tratar-se de assunto controverso, é bastante citada na literatura a maior prevalência da doença celíaca em diversos grupos de pacientes reumatológicos. OBJETIVO: Investigar a prevalência de marcadores sorológicos positivos para doença celíaca: anticorpos antigliadina (AGA) classes IgA e IgG (AGAA e AGAG) e anticorpos antiendomísio classe IgA (EmA), em pacientes com doenças reumatológicas autoimunes. Procurou-se também avaliar a correlação entre a positividade dos testes sorológicos com o uso de prednisona e de medicamentos imunossupressores. MÉTODOS: Foram avaliados 190 pacientes adultos e pediátricos com doenças reumatólogicas variadas (lúpus eritematoso sistêmico, artrite reumatóide, artrite reumatóide juvenil e espondiloartropatias. Em todos foram realizadas pesquisas de AGAA e AGAG e de EmA, encaminhando-se os casos positivos para biopsias endoscópica duodenal e estudos histológicos. RESULTADOS: Houve quatro soros positivos (2,1 por cento) para AGAA, todos com resultados negativos para AGAG e EmA. Três soros (1,6 por cento) tiveram resultados positivos para AGAG, todos com resultados negativos para AGAA e EmA. Na pesquisa de EmA, a diluição do soro em 1:2,5 mostrou resultados positivos em 94 pacientes (49,5 por cento) e na diluição de 1:5, em 41 (21,6 por cento). Em 11 indivíduos obteve-se resultado positivo para EmA na diluição 1:40 e todos eles tiveram resultado negativo para a pesquisa de anticorpos antitransglutaminase tecidual IgA (tTg). Nove dos 11 pacientes positivos para EmA e todos os 7 pacientes com anticorpos antigliadina positivos foram submetidos a biopsia duodenal endoscópica, não se constatando alterações significativas da mucosa duodenal em nenhum deles. Todos os soros positivos para EmA apresentaram resultados negativos para a pesquisa de anticorpos antitransglutaminase tecidual classe IgA (tTG). A positividade para EmA associou-se a leituras de densidade óptica mais altas para AGAA. O mesmo não foi observado para AGAG. O uso de prednisona e de imunossupressores não se relacionou às leituras de densidade óptica dos AGAA, tampouco dos AGAG. O uso dessas medicações se relacionou, contudo, a menor positividade para EmA. CONCLUSÃO: Resultados positivos para AGAA, AGAG ou EmA demonstraram-se inespecíficos para a presença de doença celíaca em pacientes com doenças reumatológicas autoimune. O uso de prednisona e drogas imunossupressoras parece diminuir a prevalência de anticorpos antiendomísio IgA, mas não de anticorpos antigliadina. Mais estudos são necessários para se avaliar com maior precisão a prevalência da doença celíaca em pacientes reumatológicos.

Lúpus eritematoso sistêmico e doença de Kikuchi-Fujimoto: relato de caso / Systemic lupus erythematosus and Kikuchi-Fujimoto disease: case report

Relata-se caso de paciente jovem que, após o diagnóstico de lúpus eritematoso sistêmico, desenvolveu linfadenomegalia dolorosa nas regiöes cervical, axilar e inguinal, acompanhada por febre, mal-estar, emagrecimento, náuseas e vômitos. A análise histológica de linfonodo cervical evidenciou doença de Kikuchi-Fujimoto. Foi realizada revisäo dos aspectos clínico-patológicos da doença de Kikuchi-Fujimoto e da linfadenopatia do lúpus eritematoso sistêmico, assim como discussäo sobre a associaçäo destas duas enfermidades, destacando-se possível ligaçäo etiológica entre elas.