2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritis

The objective of this document is to provide a comprehensive update of the recommendations of Brazilian Society of Rheumatology on drug treatment of rheumatoid arthritis (RA), based on a systematic literature review and on the opinion of a panel of rheumatologists. Four general principles and eleven recommendations were approved. General principles: RA treatment should (1) preferably consist of a multidisciplinary approach coordinated by a rheumatologist, (2) include counseling on lifestyle habits, strict control of comorbidities, and updates of the vaccination record, (3) be based on decisions shared by the patient and the physician after clarification about the disease and the available therapeutic options; (4) the goal is sustained clinical remission or, when this is not feasible, low disease activity. Recommendations: (1) the first line of treatment should be a csDMARD, started as soon as the diagnosis of RA is established; (2) methotrexate (MTX) is the first-choice csDMARD; (3) the combination of two or more csDMARDs, including MTX, may be used as the first line of treatment; (4) after failure of first-line therapy with MTX, the therapeutic strategies include combining MTX with another csDMARD (leflunomide), with two csDMARDs (hydroxychloroquine and sulfasalazine), or switching MTX for another csDMARD (leflunomide or sulfasalazine) alone; (5) after failure of two schemes with csDMARDs, a bDMARD may be preferably used or, alternatively a tsDMARD, preferably combined, in both cases, with a csDMARD; (6) the different bDMARDs in combination with MTX have similar efficacy, and therefore, the therapeutic choice should take into account the peculiarities of each drug in terms of safety and cost; (7) the combination of a bDMARD and MTX is preferred over the use of a bDMARD alone; (8) in case of failure of an initial treatment scheme with a bDMARD, a scheme with another bDMARD can be used; in cases of failure with a TNFi, a second bDMARD of the same class or with another mechanism of action is effective and safe; (9) tofacitinib can be used to treat RA after failure of bDMARD; (10) corticosteroids, preferably at low doses for the shortest possible time, should be considered during periods of disease activity, and the risk-benefit ratio should also be considered; (11) reducing or spacing out bDMARD doses is possible in patients in sustained remission

Artrite reumatóide e doenças cardiovasculares Rheumatoid arthritis and cardiovascular disease

A maior prevalência das doenças cardiovasculares, particularmente da doença coronária, está bem estabelecida na artrite reumatóide (AR). Este trabalho, envolvendo uma revisão extensa da literatura, analisa as evidências epidemiológicas apontando as doenças cardiovasculares como a maior causa de mortalidade prematura na AR, os fatores de risco para doença coronária, a relação entre aterosclerose e AR, os mecanismos fisiopatológicos desta associação, incluindo o papel direto e indireto do processo inflamatório sistêmico e as características da doença coronária na AR. Finalmente, é destacada a importância dos cuidados preventivos para este paciente reumatóide com alto risco de eventos cardiovasculares.<br>The increased prevalence of cardiovascular disease (CVD) in rheumatoid arthrtis (RA) patients is by now largely recognized. The purpose of this extensive literature review is to analyze the epidemiological evidences of CVD, particularly coronary heart disease (CHD), as the leading cause of early death in RA, the presence of coronary risk factors, the relationship between RA and atherosclerosis, the shared physiopathology mechanisms, including the systemic inflammatory process and the peculiarities of CHD in the rheumatoid population. Lastly, given the burden of cardiovascular disease in this population, it is emphasized the importance of preventive care in these high risk patients

Sarcopenia in rheumatoid cachexia: definition, mechanisms, clinical consequences and potential therapies

A caquexia relacionada à artrite reumatoide é conceituada como perda involuntária de massa magra, predominantemente de músculo esquelético, que também ocorre em vísceras e sistema imune, com massa gorda estável ou um pouco elevada e com pequena ou nenhuma perda de peso. A causa é multifatorial, incluindo a produção acentuada de citocinas, principalmente TNF± e IL-1², diminuição da ação periférica da insulina e pouca atividade física. A caquexia se faz presente em doentes com AR ativa ou mesmo inativa. Neste artigo discutem-se aspectos relacionados à patogenia, implicações clínicas e possíveis opções terapêuticas.Rheumatoid cachexia can be defined as an involuntary loss of body cell mass, which predominates in skeletal muscle, but is also observed in the viscera and immune system. It occurs with little or no weight loss in the presence of stable or increased fat mass. The etiology is likely multifactorial, and involves excessive inflammatory cytokine production, namely excess tumor necrosis factor-± and interleukin-1² production, reduced peripheral insulin action, and low habitual physical activity. Cachexia occurs in active rheumatoid arthritis and even in the presence of disease control. In this article, we discuss the pathogenesis of rheumatoid cachexia, its clinical implications and potential therapies

National recommendations based on scientific evidence and opinions of experts on the use of methotrexate in rheumatic disorders, especially in rheumatoid arthritis : results of the 3E Initiative from Brazil

Objetivos: A utilização do metotrexato (MTX) tem sido a base da terapia da artrite reumatoide (AR), porém ainda não temos uniformidade sobre as normas para seu uso clínico. O objetivo deste estudo foi criar recomendações baseadas em evidências científicas e opiniões de especialistas (experts) sobre o uso do MTX, as quais permitirão melhorar nossa prática clínica. Métodos: O 3E (Evidence, Expertise, Exchange) Initiative in Rheumatology é um grupo multinacional de reumatologistas oriundos de 17 países, incluindo o Brasil. Após uma seleção de dez questões sobre o uso de MTX, feita pelo método Delphi, realizou-se uma revisão sistemática da literatura (RSL) (Medline, Pubmed, Embase, Cochrane, Abstracts EULAR 2005-2007 e ACR 2006-2007) por seis revisores bibliográficos internacionais escolhidos pelos men¬tores do estudo 3E. Duas diferentes questões nacionais do Brasil também foram incluídas e essa pesquisa foi realizada por um revisor bibliográfico nacional.** Os resultados da RSL foram apresentados por sete membros do comitê cien¬tífico brasileiro do 3E*, em um encontro nacional de 48 reumatologistas, os quais discutiram as informações da RSL, votaram e elaboraram recomendações nacionais aqui apresentadas. Estas foram utilizadas posteriormente na criação de recomendações multinacionais. Resultados e conclusões: Formularam-se 21 recomendações acerca das dez questões internacionais e das duas questões nacionais, com um nível de concordância entre os participantes de 77% (63 a 100%). O MTX é indicado inicialmente por via oral, na dose mínima de 10 mg/sem e máxima de 25 mg/sem. A elevação de AST/ALT acima de 3 vezes o limite superior do valor normal, por pelo menos três vezes, justifica a suspensão temporária do MTX, podendo-se reinstituir com a normalização dos valores encontrados. MTX é seguro a longo prazo. O uso de álcool (> 100 g/sem) deve ser evitado. Recomenda-se combinação do MTX com drogas antirreumáticas modificadoras da doença (DMARDs), embora haja risco de maior toxicidade. Ácido fólico em dose maior que 5 mg/sem deve ser associado. Devem-se solicitar hemograma, creatinina, AST/ALT, sorologia para vírus B e C da hepatite e raio X de tórax antes de iniciar o MTX, e deve-se inquirir sobre contracepção, comorbidades, uso de drogas ilícitas e álcool, hepatopatias e medicamentos hepatotóxicos. O MTX pode ser mantido durante cirurgias eletivas. Sugere-se a interrupção do MTX por, pelo menos, três meses antes do planejamento de gravidez, tanto em homens quanto em mulheres. Justifica-se a utilização de métodos de contracepção com o uso de MTX em idade reprodutiva. Pode-se usar MTX como poupador de corticoide em pacientes com arterite de células gigantes, polimialgia reumática (PMR), dermatomiosite juvenil e lúpus eritematoso sistêmico (LES) com envolvimento cutâneo e/ou articular.Objectives: The use of methotrexate (MTX) has been the basis for rheumatoid arthritis (RA) therapy, but there is no uniformity on the guidelines for its clinical use. The objective of this study was to develop recommendations based on scientific evidence and opinions of experts on the use of MTX, which will allow the improvement of our clinical practice. Methods: 3E (Evidence, Expertise, Exchange) Initiative in Rheumatology is a multinational group of rheumatologists from 17 countries, including Brazil. After a selection of 10 questions about the use of MTX, held by the Delphi method, a systematic literature review (SLR) was done (Medline, Pubmed, Embase, Cochrane, Abstracts EULAR 2005-2007 and ACR 2006-2007) by six international bibliographic reviewers chosen by the mentors of the 3E study. Two other different national questions from Brazil were also included, and the SLR was done by a national bibliographic reviewer.** The results of SLR were presented by 7 members of our Brazilian 3E scientific committee* at a meeting of 48 rheumatologists, which discussed RSL details, voted, and produced the national recommendations presented here. These recommendations were subsequently used in the creation of multinational recommendations. Results and conclusions: 21 recommendations concerning the 10 international and the 2 national questions were formulated, with an agreement level of 77% among the participants (63-100%). Oral MTX should be started at a minimum dose of 10 mg/wk and a maximum dose of 25 mg/wk. Elevation of AST/ALT above 3x the upper limit, for at least 3 times consecutively, justifies the temporary suspension of MTX, which can be restored after normalization of serum liver enzyme levels; MTX is safe for long term use. The use of alcohol (100 g/wk) should be avoided. Combinations of MTX with disease modifying antirheumatic drugs are recommended, although there is risk of greater toxicity. Folic acid should be associated with MTX in dose higher than 5 mg/wk. Total blood cell count, creatinine, AST/ALT, serology for hepatitis B and C virus, and chest X-ray should be ordered before initiating MTX. Inquire about contraception methods, comorbidities, use of illicit drugs, alcohol, and liver diseases and hepatotoxic drugs should be performed. The MTX can be maintained during elective surgeries; discontinuation of MTX for at least 3 months before planning of pregnancy is suggested, for both men and women Use of contraception method is justified with the use of MTX in reproductive age. MTX can be used to reduce the cumulative dose of corticosteroid in patients with giant cell arthritis, rheumatic polymyalgia (RPM), juvenile dermatomyositis, and in systemic lupus erythematosus (SLE) with cutaneous or joint involvement

National recommendations based on scientific evidence and opinions of experts on the use of methotrexate in rheumatic disorders, especially in rheumatoid arthritis : results of the 3E Initiative from Brazil

Objetivos: A utilização do metotrexato (MTX) tem sido a base da terapia da artrite reumatoide (AR), porém ainda não temos uniformidade sobre as normas para seu uso clínico. O objetivo deste estudo foi criar recomendações baseadas em evidências científicas e opiniões de especialistas (experts) sobre o uso do MTX, as quais permitirão melhorar nossa prática clínica. Métodos: O 3E (Evidence, Expertise, Exchange) Initiative in Rheumatology é um grupo multinacional de reumatologistas oriundos de 17 países, incluindo o Brasil. Após uma seleção de dez questões sobre o uso de MTX, feita pelo método Delphi, realizou-se uma revisão sistemática da literatura (RSL) (Medline, Pubmed, Embase, Cochrane, Abstracts EULAR 2005-2007 e ACR 2006-2007) por seis revisores bibliográficos internacionais escolhidos pelos men¬tores do estudo 3E. Duas diferentes questões nacionais do Brasil também foram incluídas e essa pesquisa foi realizada por um revisor bibliográfico nacional.** Os resultados da RSL foram apresentados por sete membros do comitê cien¬tífico brasileiro do 3E*, em um encontro nacional de 48 reumatologistas, os quais discutiram as informações da RSL, votaram e elaboraram recomendações nacionais aqui apresentadas. Estas foram utilizadas posteriormente na criação de recomendações multinacionais. Resultados e conclusões: Formularam-se 21 recomendações acerca das dez questões internacionais e das duas questões nacionais, com um nível de concordância entre os participantes de 77% (63 a 100%). O MTX é indicado inicialmente por via oral, na dose mínima de 10 mg/sem e máxima de 25 mg/sem. A elevação de AST/ALT acima de 3 vezes o limite superior do valor normal, por pelo menos três vezes, justifica a suspensão temporária do MTX, podendo-se reinstituir com a normalização dos valores encontrados. MTX é seguro a longo prazo. O uso de álcool (> 100 g/sem) deve ser evitado. Recomenda-se combinação do MTX com drogas antirreumáticas modificadoras da doença (DMARDs), embora haja risco de maior toxicidade. Ácido fólico em dose maior que 5 mg/sem deve ser associado. Devem-se solicitar hemograma, creatinina, AST/ALT, sorologia para vírus B e C da hepatite e raio X de tórax antes de iniciar o MTX, e deve-se inquirir sobre contracepção, comorbidades, uso de drogas ilícitas e álcool, hepatopatias e medicamentos hepatotóxicos. O MTX pode ser mantido durante cirurgias eletivas. Sugere-se a interrupção do MTX por, pelo menos, três meses antes do planejamento de gravidez, tanto em homens quanto em mulheres. Justifica-se a utilização de métodos de contracepção com o uso de MTX em idade reprodutiva. Pode-se usar MTX como poupador de corticoide em pacientes com arterite de células gigantes, polimialgia reumática (PMR), dermatomiosite juvenil e lúpus eritematoso sistêmico (LES) com envolvimento cutâneo e/ou articular.Objectives: The use of methotrexate (MTX) has been the basis for rheumatoid arthritis (RA) therapy, but there is no uniformity on the guidelines for its clinical use. The objective of this study was to develop recommendations based on scientific evidence and opinions of experts on the use of MTX, which will allow the improvement of our clinical practice. Methods: 3E (Evidence, Expertise, Exchange) Initiative in Rheumatology is a multinational group of rheumatologists from 17 countries, including Brazil. After a selection of 10 questions about the use of MTX, held by the Delphi method, a systematic literature review (SLR) was done (Medline, Pubmed, Embase, Cochrane, Abstracts EULAR 2005-2007 and ACR 2006-2007) by six international bibliographic reviewers chosen by the mentors of the 3E study. Two other different national questions from Brazil were also included, and the SLR was done by a national bibliographic reviewer.** The results of SLR were presented by 7 members of our Brazilian 3E scientific committee* at a meeting of 48 rheumatologists, which discussed RSL details, voted, and produced the national recommendations presented here. These recommendations were subsequently used in the creation of multinational recommendations. Results and conclusions: 21 recommendations concerning the 10 international and the 2 national questions were formulated, with an agreement level of 77% among the participants (63-100%). Oral MTX should be started at a minimum dose of 10 mg/wk and a maximum dose of 25 mg/wk. Elevation of AST/ALT above 3x the upper limit, for at least 3 times consecutively, justifies the temporary suspension of MTX, which can be restored after normalization of serum liver enzyme levels; MTX is safe for long term use. The use of alcohol (100 g/wk) should be avoided. Combinations of MTX with disease modifying antirheumatic drugs are recommended, although there is risk of greater toxicity. Folic acid should be associated with MTX in dose higher than 5 mg/wk. Total blood cell count, creatinine, AST/ALT, serology for hepatitis B and C virus, and chest X-ray should be ordered before initiating MTX. Inquire about contraception methods, comorbidities, use of illicit drugs, alcohol, and liver diseases and hepatotoxic drugs should be performed. The MTX can be maintained during elective surgeries; discontinuation of MTX for at least 3 months before planning of pregnancy is suggested, for both men and women Use of contraception method is justified with the use of MTX in reproductive age. MTX can be used to reduce the cumulative dose of corticosteroid in patients with giant cell arthritis, rheumatic polymyalgia (RPM), juvenile dermatomyositis, and in systemic lupus erythematosus (SLE) with cutaneous or joint involvement

2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritis

The objective of this document is to provide a comprehensive update of the recommendations of Brazilian Society of Rheumatology on drug treatment of rheumatoid arthritis (RA), based on a systematic literature review and on the opinion of a panel of rheumatologists. Four general principles and eleven recommendations were approved. General principles: RA treatment should (1) preferably consist of a multidisciplinary approach coordinated by a rheumatologist, (2) include counseling on lifestyle habits, strict control of comorbidities, and updates of the vaccination record, (3) be based on decisions shared by the patient and the physician after clarification about the disease and the available therapeutic options; (4) the goal is sustained clinical remission or, when this is not feasible, low disease activity. Recommendations: (1) the first line of treatment should be a csDMARD, started as soon as the diagnosis of RA is established; (2) methotrexate (MTX) is the first-choice csDMARD; (3) the combination of two or more csDMARDs, including MTX, may be used as the first line of treatment; (4) after failure of first-line therapy with MTX, the therapeutic strategies include combining MTX with another csDMARD (leflunomide), with two csDMARDs (hydroxychloroquine and sulfasalazine), or switching MTX for another csDMARD (leflunomide or sulfasalazine) alone; (5) after failure of two schemes with csDMARDs, a bDMARD may be preferably used or, alternatively a tsDMARD, preferably combined, in both cases, with a csDMARD; (6) the different bDMARDs in combination with MTX have similar efficacy, and therefore, the therapeutic choice should take into account the peculiarities of each drug in terms of safety and cost; (7) the combination of a bDMARD and MTX is preferred over the use of a bDMARD alone; (8) in case of failure of an initial treatment scheme with a bDMARD, a scheme with another bDMARD can be used; in cases of failure with a TNFi, a second bDMARD of the same class or with another mechanism of action is effective and safe; (9) tofacitinib can be used to treat RA after failure of bDMARD; (10) corticosteroids, preferably at low doses for the shortest possible time, should be considered during periods of disease activity, and the risk-benefit ratio should also be considered; (11) reducing or spacing out bDMARD doses is possible in patients in sustained remission