Abstract Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

Abstract 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.

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.

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.

OBJETIVO: Elaborar recomendações para a vacinação em pacientes com artrite reumatoide (AR) no Brasil. MÉTODO: Revisão da literatura e opinião de especialistas membros da Comissão de AR da Sociedade Brasileira de Reumatologia e um pediatra reumatologista. RESULTADOS E CONCLUSÕES: Foram estabelecidas 12 recomendações: 1) Antes de iniciar drogas modificadoras do curso de doença, deve-se revisar e atualizar o cartão vacinal; 2) As vacinas contra influenza sazonal e contra H1N1 estão indicadas anualmente para pacientes portadores de AR; 3) A vacina antipneumocócica deve ser indicada para todos os pacientes; 4) A vacina contra varicela deve ser indicada para pacientes com história negativa ou duvidosa de infecção prévia por varicela; 5) A vacina contra HPV deve ser considerada em adolescentes e mulheres jovens; 6) A vacina antimeningocócica é indicada para pacientes portadores de AR apenas em casos de asplenia ou deficiência de complemento; 7) Existe orientação de imunização contra o Haemophilus influenzae tipo B de pacientes adultos asplênicos; 8) Não há indicação de uma vacina adicional contra BCG em pacientes com AR; 9) A vacina contra hepatite B é indicada para pacientes com anticorpos contra HBsAg negativos; considerar a vacina contra hepatite A em combinação com a hepatite B; 10) Pacientes com grande risco de contrair tétano que receberam rituximabe nas últimas 24 semanas devem utilizar imunização passiva com imunoglobulina antitetânica; 11) A vacina contra febre amarela é contraindicada nos pacientes com AR em uso de imunossupressores; 12) As recomendações acima descritas devem ser revisadas ao longo da evolução da AR.

OBJECTIVE: To elaborate recommendations to the vaccination of patients with rheumatoid arthritis (RA) in Brazil. METHOD: Literature review and opinion of expert members of the Brazilian Society of Rheumatology Committee of Rheumatoid Arthritis and of an invited pediatric rheumatologist. RESULTS AND CONCLUSIONS: The following 12 recommendations were established: 1) Before starting disease-modifying anti-rheumatic drugs, the vaccine card should be reviewed and updated; 2) Vaccines against seasonal influenza and against H1N1 are indicated annually for patients with RA; 3) The pneumococcal vaccine should be indicated for all patients with RA; 4) The vaccine against varicella should be indicated for patients with RA and a negative or dubious history for that disease; 5) The HPV vaccine should be considered for adolescent and young females with RA; 6) The meningococcal vaccine is indicated for patients with RA only in the presence of asplenia or complement deficiency; 7) Asplenic adults with RA should be immunized against Haemophilus influenzae type B; 8) An additional BCG vaccine is not indicated for patients diagnosed with RA; 9) Hepatitis B vaccine is indicated for patients with RA who are negative for antibodies against HBsAg; the combined hepatitis A and B vaccine should be considered; 10) Patients with RA and at high risk for tetanus, who received rituximab in the preceding 24 weeks, should undergo passive immunization with tetanus immunoglobulin in case of exposure; 11) The YF vaccine is contraindicated to patients with RA on immunosuppressive drugs; 12) The above described recommendations should be reviewed over the course of RA.