Do it fast! Early access to specialized care improved long-term outcomes in rheumatoid arthritis: data from the REAL multicenter observational study

Abstract Background Early rheumatoid arthritis (RA) offers an opportunity for better treatment outcomes. In real-life settings, grasping this opportunity might depend on access to specialized care. We evaluated the effects of early versus late assessment by the rheumatologist on the diagnosis, treatment initiation and long-term outcomes of RA under real-life conditions. Methods Adults meeting the ACR/EULAR (2010) or ARA (1987) criteria for RA were included. Structured interviews were conducted. The specialized assessment was deemed "early" when the rheumatologist was the first or second physician consulted after symptoms onset, and "late" when performed afterwards. Delays in RA diagnosis and treatment were inquired. Disease activity (DAS28-CRP) and physical function (HAQ-DI) were evaluated. Student's t, Mann-Whitney U, chi-squared and correlation tests, and multiple linear regression were performed. For sensitivity analysis, a propensity score-matched subsample of early- vs. late-assessed participants was derived based on logistic regression. The study received ethical approval; all participants signed informed consent. Results We included 1057 participants (89.4% female, 56.5% white); mean (SD) age: 56.9 (11.5) years; disease duration: 173.1 (114.5) months. Median (IQR) delays from symptoms onset to both RA diagnosis and initial treatment coincided: 12 (6-36) months, with no significant delay between diagnosis and treatment. Most participants (64.6%) first sought a general practitioner. Notwithstanding, 80.7% had the diagnosis established only by the rheumatologist. Only a minority (28.7%) attained early RA treatment (≤ 6 months of symptoms). Diagnostic and treatment delays were strongly correlated (rho 0.816; p < 0.001). The chances of missing early treatment more than doubled when the assessment by the rheumatologist was belated (OR 2.77; 95% CI: 1.93, 3.97). After long disease duration, late-assessed participants still presented lower chances of remission/low disease activity (OR 0.74; 95% CI: 0.55, 0.99), while the early-assessed ones showed better DAS28-CRP and HAQ-DI scores (difference in means [95% CI]: −0.25 [−0.46, −0.04] and − 0.196 [−0.306, −0.087] respectively). The results in the propensity-score matched subsample confirmed those observed in the original (whole) sample. Conclusions Early diagnosis and treatment initiation in patients with RA was critically dependent on early access to the rheumatologist; late specialized assessment was associated with worse long-term clinical outcomes.

Decreasing delays in the diagnosis and treatment of rheumatoid arthritis in Brazil: a nationwide multicenter observational study

Abstract Background Management delays imply worse outcomes in rheumatoid arthritis (RA) and, therefore, should be minimized. We evaluated changes in diagnostic and treatment delays regarding RA in the last decades in Brazil. Methods Adults fulfilling the ACR/EULAR (2010) criteria for RA were assessed. Delays in diagnosis and treatment, and the frequencies of early management initiation within thresholds (windows of opportunity) of 3, 6, and 12 months from symptoms onset were evaluated. The Mann-Kendall trend test, chi-squared tests with Cramer's V effect sizes and analysis of variance were conducted. Results We included 1116 patients: 89.4% female, 56.8% white, mean (SD) age 57.1 (11.5) years. A downward trend was found in diagnostic (tau = - 0.677, p < 0.001) and treatment (tau = - 0.695, p < 0.001) delays from 1990 to 2015. The frequency of early management increased throughout the period, with ascending effect sizes across the 3-, 6-, and 12-month windows (V = 0.120, 0.200 and 0.261, respectively). Despite all improvements, even in recent years (2011-2015) the diagnostic and treatment delays still remained unacceptably high [median (IQR): 8 (4-12) and 11 (5-17) months, respectively], with only 17.2% of the patients treated within the shortest, 3-month window. Conclusion The delays in diagnosis and treatment of RA decreased during the last decades in Brazil. Improvements (effect sizes) were greater at eliminating extreme delays (≥ 12 months) than in attaining really short management windows (≤ 3 months). Very early treatment was still an unrealistic goal for most patients with RA.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort

Abstract Introduction Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. Objective To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. Method Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whit-ney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). Results 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. Conclusions ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force

Abstract Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle-Ottawa Scale to assess the quality of nonrandomized studies. Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4—agree—and 5—strongly agree—, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.

Cardiovascular risk comorbidities in rheumatoid arthritis patients and the use of anti-rheumatic drugs: a cross-sectional real- life study

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune systemic inflammatory disease. In addition to joint involvement, RA patients frequently have other comorbidities, such as cardiovascular diseases. Drugs used for RA treatment may increase or decrease the risk of a cardiovascular event. This study aims to analyze cardiovascular risk comorbidities in patients with RA and the correlation with the use of anti-rheumatic drugs. Methods: Cross-sectional study conducted based on the real-life rheumatoid arthritis study database - REAL, a prospective observational cohort study. Associations between the use of anti-rheumatic drugs and the presence of comorbidities were represented by their prevalence ratio and evaluated using the Chi-square or Fisher's Exact tests. Results: We assessed 1116 patients, 89.4% women, mean age of 55.15 years and predominance of seropositive disease. 63.3% had some cardiovascular comorbidity, predominantly hypertension (49.9%). The use of glucocorticoids was observed in 47.4% of patients and there was a significant tendency of lower use of these drugs in the presence of dyslipidemia (PR: 0.790; p = 0.007). We observed that the presence of cardiovascular comorbidities was associated with higher use of bDMARDs (PR:1.147; p = 0.003). Conclusions: The presence of cardiovascular risk comorbidities was confirmed to be higher in RA patients. Different treatment strategies using less glucocorticoids in the presence of dyslipidemia and more common use of bDMARDs in patients with cardiovascular comorbidities suggest that rheumatologists are aware of the potential influence of the DMARDs in the risk of cardiovascular event. Reinforcing these results, we highlight the need for a better baseline assessment to guide the choice of anti-rheumatic drugs in RA patients who have comorbidities.

Rheumatoid artrhitis treatment in Brazil: data from a large real-life multicenter study

Abstract Background: Last decades witnessed great technological advances in rheumatoid arthritis (RA) management, but their implementation in clinical practice might prove difficult. Despite the efficacy demonstrated in controlled trials this information needs to be confirmed by real life data. This study assessed real-life treatment among RA patients. Methods: REAL study included Brazilian RA patients from eleven centers. Interview and medical records were performed. Continuous variables were compared using Student's t or Mann-Whitney and categorical variables were assessed with chi-square or Fisher's exact tests. Results: 1115 patients were included, women 89.5%. Median age 56.6 years, disease duration 152.5 months; 78.7% were rheumatoid fator positive; 55.2% had erosive disease; DAS28 (disease activity index-28 joints) = 3.5, HAQ (health assessment questionnaire) =0.875. The median duration of symptoms until the start of first DMARD was 12 months. A total of 529 (47.2%) patients used corticosteroids; 1022 (90.8%) were on conventional synthetic (cs) DMARDs and 406 (36.1%) on biological (b) DMARDs. Methotrexate (MTX) was the most frequent csDMARD: 748 (66.5%) patients, followed by leflunomide (LFN), used by 381 (33.9%) of patients. MTX was associated to LFN in 142 (12.6%) patients. Only five (0.4%) patients used triple therapy (MTX + hydroxychloroquine + sulfasalazine) or sulfasalazine in monotherapy. Conclusions: Despite advances in therapeutic resources, roughly half RA patients failed achieve T2T goals and 55.2% developed erosive disease. The frequent use of corticosteroids and delay in initiating DMARDs were demonstrated. Issues concerning timely access to medical care are crucial for effective management.(AU)

Real - rheumatoid arthritis in real life -study cohort: a sociodemographic profile of rheumatoid arthritis in Brazil

Abstract Background: In Brazil, socioeconomic differences in the incidence of rheumatoid arthritis (RA) have been demonstrated, which are important in the formulation of hypotheses regarding the association between environmental factors, lifestyle and the risk of disease development. This study examines how the socioeconomic condition of the patient with RA in Brazil, assessed according to social class, educational level, employment situation and use of caregivers, affects the times between the beginning of symptoms and diagnosis and the beginning of the use of disease-modifying antirheumatic drugs, as well as the presence of erosive disease and functional status. Methods: This work is part of a multicentric study called REAL - Rheumatoid Arthritis in Real Life in Brazil, which is a prospective observational cohort study. Results: As described in the REAL study, we included a total of 1115 patients. It was noted that patients with an educational classification of up to second grade incomplete presented with erosion percentages above those with a higher grade complete. Patients with caregivers presented a higher percentage of erosion than patients without caregivers. We verified that patients from economic classes above B2 presented fewer occurrences of erosion than those from classes C2, D-E. We also analyzed the average time differences from the beginning of symptoms and diagnosis and the beginning of treatment, according to academic level, erosion and economic classification. Patients with first grade complete showed an HAQ-DI averages higher than those with second grade complete. The patients who had employment showed lower HAQ-DI averages than patients who were not employed. The patients with erosion showed an HAQ-DI value higher than those without erosion. Patients with caregivers showed an HAQ-DI average higher than that of without caregivers. Conclusion: This study showed that the therapeutic window of RA is not being reached, and therefore we should have a policy to expand and ensure access to public health for all patients, especially those with lower levels of education and income. Trial registration: This study was approved by the National Commission of Ethics in Research.(AU)

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.

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.

Consenso 2012 da Sociedade Brasileira de Reumatologia sobre vacinação em pacientes com artrite reumatoide / 2012 Brazilian Society of Rheumatology Consensus on vaccination of patients with rheumatoid arthritis

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.

Consenso 2012 da Sociedade Brasileira de Reumatologia sobre o manejo de comorbidades em pacientes com artrite reumatoide / 2012 Brazilian Society of Rheumatology Consensus on the management of comorbidities in patients with rheumatoid arthritis

OBJETIVO: Elaborar recomendações da Comissão de Artrite Reumatoide da Sociedade Brasileira de Reumatologia (SBR) para o manuseio das comorbidades em artrite reumatoide (AR). MÉTODOS: Revisão da literatura e opinião de especialistas da Comissão de AR da SBR. RESULTADOS E CONCLUSÕES: Recomendações: 1) Diagnosticar e tratar precoce e adequadamente as comorbidades; 2) O tratamento específico da AR deve ser adaptado às comorbidades; 3) Inibidores da enzima conversora da angiotensina (IECA) ou bloqueadores dos receptores de angiotensina II (BRA) são preferidos no tratamento da hipertensão arterial sistêmica; 4) Em pacientes com AR e diabetes mellitus, deve-se evitar o uso contínuo de dose cumulativa alta de corticoides; 5) Sugere-se o uso de estatinas para manter níveis de LDL menor que 100 mg/dL e índice aterosclerótico menor que 3,5 em pacientes com AR e comorbidades; 6) A síndrome metabólica deve ser tratada; 7) Recomenda-se a realização de exames para a investigação de aterosclerose subclínica; 8) Maior vigilância para um diagnóstico precoce de neoplasia oculta; 9) Medidas de prevenção para trombose venosa são sugeridas; 10) Recomenda-se a realização de densitometria óssea em pacientes com AR acima de 50 anos, e naqueles com idade menor com corticoide maior que 7,5 mg por mais de três meses; 11) Pacientes com AR e osteoporose devem evitar quedas, e devem ser aconselhados a aumentarem a ingestão de cálcio, aumentarem a exposição solar e fazerem atividade física; 12) Suplementação de cálcio e vitamina D é sugerida.Autilização de bisfosfonatos é sugerida para pacientes com escore T menor que -2,5 na densidade mineral óssea; 13) Recomenda-se equipe multidisciplinar, com participação ativa do médico reumatologista no tratamento das comorbidades.

OBJECTIVE: To elaborate recommendations of the Rheumatoid Arthritis Committee of the Brazilian Society of Rheumatology (SBR) to manage comorbidities in rheumatoid arthritis (RA). METHODS: To review the literature and the opinions of the SBR RA Committee experts. RESULTS AND CONCLUSIONS: Recommendations: 1) Early diagnosis and proper treatment of comorbidities are recommended; 2) The specific treatment of RA should be adapted to the presence of comorbidities; 3) Angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers are preferred to treat systemic arterial hypertension; 4) In patients diagnosed with rheumatoid arthritis and diabetes mellitus, the continuous use of a high cumulative dose of corticoids should be avoided; 5) Statins should be used to maintain LDL cholesterol levels under 100 mg/dL and the atherosclerotic index lower than 3.5 in patients with RA who have other comorbidities; 6) Metabolic syndrome should be treated; 7) Performing non-invasive tests to investigate subclinical atherosclerosis is recommended; 8) Greater surveillance for the early diagnosis of occult malignancy is recommended; 9) Preventive measures of venous thrombosis are suggested; 10) Bone densitometry is recommended in RA patients over the age of 50 years and in younger patients on corticoid therapy at a dose greater than 7.5 mg for over three months; 11) Patients with RA and osteoporosis should be instructed to avoid falls, to increase their dietary calcium intake and sun exposure, and to exercise; 12) Calcium and vitamin D supplementation is suggested. Bisphosphonates are suggested for patients with T score < -2.5 on bone densitometry; 13) A multidisciplinary team, with the active participation of a rheumatologist, is recommended to treat comorbidities.

Consenso 2012 da Sociedade Brasileira de Reumatologia para o tratamento da artrite reumatoide / 2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis

OBJETIVO: Elaborar recomendações para o tratamento da artrite reumatoide no Brasil. MÉTODO: Revisão da literatura com seleção de artigos baseados em evidência e opinião de especialistas da Comissão de Artrite Reumatoide da Sociedade Brasileira de Reumatologia. RESULTADOS E CONCLUSÕES: 1) A decisão terapêutica deve ser compartilhada com o paciente; 2) imediatamente após o diagnóstico, uma droga modificadora do curso da doença (DMCD) deve ser prescrita e o tratamento ajustado para atingir remissão; 3) o tratamento deverá ser conduzido por reumatologista; 4) o tratamento inicial inclui DMCD sintéticas; 5) o metotrexato é a droga de escolha; 6) pacientes que não alcançaram resposta após a utilização de dois esquemas de DMCD sintéticas devem ser avaliados para DMCD biológicas; 7) excepcionalmente, DMCD biológicas poderão ser consideradas mais precocemente; 8) recomenda-se preferencialmente o uso de agentes anti-TNF como terapia biológica inicial; 9) após falha terapêutica a uma primeira DMCD biológica, outros biológicos poderão ser utilizados; 10) ciclofosfamida e azatioprina podem ser consideradas em manifestações extra-articulares graves; 11) recomenda-se a utilização de corticoide oral em baixas doses e por curtos períodos; 12) os anti-inflamatórios não hormonais devem sempre ser prescritos em associação à DMCD; 13) avaliações clínicas devem ser mensais no início do tratamento; 14) terapia física, reabilitação e terapia ocupacional são indicadas; 15) deve-se recomendar tratamento cirúrgico para correção de sequelas; 16) métodos de terapia alternativa não substituem a terapia tradicional; 17) deve-se orientar planejamento familiar; 18) orienta-se a busca ativa e o manejo de comorbidades; 19) atualizar e documentar a vacinação do paciente; 20) doenças transmissíveis endêmico-epidêmicas devem ser investigadas e tratadas.

OBJECTIVE: To elaborate recommendations for the treatment of rheumatoid arthritis in Brazil. METHOD: Literature review with articles' selection based on evidence and the expert opinion of the Rheumatoid Arthritis Committee of the Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: 1) The therapeutic decision should be shared with the patient; 2) immediately after the diagnosis, a disease-modifying antirheumatic drug (DMARD) should be prescribed, and the treatment adjusted to achieve remission; 3) treatment should be conducted by a rheumatologist; 4) the initial treatment includes synthetic DMARDs; 5) methotrexate is the drug of choice; 6) patients who fail to respond after two schedules of synthetic DMARDs should be assessed for the use of biologic DMARDs; 7) exceptionally, biologic DMARDs can be considered earlier; 8) anti-TNF agents are preferentially recommended as the initial biologic therapy; 9) after therapeutic failure of a first biologic DMARD, other biologics can be used; 10) cyclophosphamide and azathioprine can be used in severe extra-articular manifestations; 11) oral corticoid is recommended at low doses and for short periods of time; 12) non-steroidal anti-inflammatory drugs should always be prescribed in association with a DMARD; 13) clinical assessments should be performed on a monthly basis at the beginning of treatment; 14) physical therapy, rehabilitation, and occupational therapy are indicated; 15) surgical treatment is recommended to correct sequelae; 16) alternative therapy does not replace traditional therapy; 17) family planning is recommended; 18) the active search and management of comorbidities are recommended; 19) the patient's vaccination status should be recorded and updated; 20) endemic-epidemic transmissible diseases should be investigated and treated.

Consenso da Sociedade Brasileira de Reumatologia 2011 para o diagnóstico e avaliação inicial da artrite reumatoide / 2011 Consensus of the Brazilian Society of Rheumatology for diagnosis and early assessment of rheumatoid arthritis

OBJETIVO: Elaborar recomendações para o manejo da artrite reumatoide (AR) no Brasil, com enfoque no diagnóstico e na avaliação inicial da doença. MÉTODO: Revisão da literatura e opinião de especialistas membros da Comissão de AR da Sociedade Brasileira de Reumatologia. RESULTADOS E CONCLUSÕES: Foram estabelecidas 10 recomendações: 1) O diagnóstico da AR deve ser estabelecido considerando-se achados clínicos e exames complementares; 2) Deve-se dedicar especial atenção ao diagnóstico diferencial dos casos de artrite; 3) O fator reumatoide (FR) é um teste diagnóstico importante, porém com sensibilidade e especificidade limitadas, sobretudo na AR inicial; 4) O anti-CCP (teste para anticorpos antipeptídeos citrulinados cíclicos) é um marcador com sensibilidade semelhante a do FR, mas com especificidade superior, sobretudo na fase inicial da doença; 5) Embora inespecíficas, provas de atividade inflamatória devem ser solicitadas a pacientes com suspeita clínica de AR; 6) A radiografia convencional deve ser empregada para avaliação de diagnóstico e prognóstico da doença. Quando necessário e disponível, a ultrassonografia e a ressonância magnética podem ser utilizadas; 7) Podem-se utilizar critérios de classificação de AR (ACR/EULAR 2010), embora ainda não validados, como um guia para auxiliar no diagnóstico de pacientes com artrite inicial; 8) Deve-se utilizar um dos índices compostos para avaliação de atividade de doença; 9) Recomenda-se a utilização regular de ao menos um instrumento de avaliação da capacidade funcional; 10) Deve-se verificar, na avaliação inicial da doença, a presença ou não de fatores de pior prognóstico, como o acometimento poliarticular, FR e/ou anti-CCP em títulos elevados e erosão articular precoce.

OBJECTIVE: Develop guidelines for management of rheumatoid arthritis (RA) in Brazil, focusing on diagnosis and early assessment of the disease. METHOD: Literature review and expert opinions of RA Committee members of the Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: The following ten reccommendations were established: 1) RA diagnosis should be established considering clinical findings and complementary test results; 2) Special attention should be given to the differential diagnosis of arthritis; 3) Rheumatoid factor (RF) is an important diagnostic test, but has limited sensitivity and specificity, mainly in early RA; 4) Anti-CCP (anti-cyclic citrullinated peptide antibody) is a marker with sensitivity similar to that of the RF, but with higher specificity, mainly in the initial phase of disease; 5) Although unspecific, acute-phase reactants should be measured in patients with clinical suspicion of RA; 6) Conventional radiography should be performed for diagnostic and prognostic assessment of the disease. When necessary and available, ultrasound and magnetic resonance may be used; 7) Rheumatoid arthritis classification criteria (ACR/EULAR 2010), although not yet validated, may be used as a guide to aid in diagnosing patients with early RA; 8) One of the combined disease activity indices should be used to assess disease activity; 9) At least one of the functional capacity assessment instruments, such as mHAQ or HAQ-DI, should be regularly used; 10) At the early assessment of the disease, the presence of worse prognostic factors, such as polyarticular involvement, high titers of RF and/or anti-CCP, and early joint erosion, should be investigated.

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 / Recomendações nacionais baseadas em evidências científicas e opiniões dos especialistas sobre o uso do metotrexato nas doenças reumáticas, especialmente na artrite reumatoide: resultados da iniciativa 3E do Brasil

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 mentores 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 científico 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...

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...

Antiinflamatórios não hormonais / Nonsteroidal anti-infl ammatory drugs

Os fármacos antiinflamatórios não hormonais fazem parte de um grupode medicamentos dos mais comercializados em todo o mundo. NosEstados Unidos, estima-se que cerca de 17 milhões de pessoas usamessas substâncias diariamente, pois várias delas podem ser obtidassem prescrições. Calcula-se, por outro lado, que aproximadamente 60milhões de prescrições sejam feitas anualmente. A maioria a utilizálassão adultos idosos. Estes fármacos têm se mostrado efi cazes nocontrole de dores infl amatórias, agudas e crônicas, em particular asmúsculo esqueléticas.

Antiinflamatórios hormonais: Glicocorticóides / Steroidal antiinfl ammatory drugs: glucocorticoids

Os gicocorticóides são drogas amplamente usadas em função de seusefeitos imunossupressivos e antiinfamatórios no tratamento de muitasdoenças reumáticas, além de outras doenças infl amatórias. Contudo, seu uso é muitas vezes limitado por numerosas reações adversas que provoca. No presente capítulo, são abordados aspectos fi siológicos e farmacológicos, mecanismo de ação dos glicocorticóides, bem como suas formas de administração e, em especial, as indicações para o uso de glicocorticosteróides em doenças reumáticas do idoso. As interações medicamentosas e os efeitos adversos são discutidos.

Consenso brasileiro para diagnóstico e tratamento da artrite reumatóide / Brazilian consensus for the diagnosis and treatment of rheumatoid arthritis

Objetivo: Estabelecer diretrizes claras e sucintas para o diagnóstico e o tratamento da artrite reumatóide. Métodos: Reunião consensual e multidisciplinar com a participação de médicos reumatologistas, fisiatras e ortopedistas para elaboração do texto final. A partir de textos recentes (Guidelines for the management of rheumatoid arthritis, do Colégio Americano de Reumatologia, e das diretrizes para o diagnóstico e tratamento da artrite reumatóide do Ministério da Saúde) e baseados em extensa revisπo bibliográfica, com prioridade para metanálises, os participantes, divididos em três grupos, produziram um texto de trabalho, cujas recomendações foram submetidas à aprovação geral dos participantes, sofrendo uma revisão geral. Resultados: Obteve-se, assim, um texto básico, que vinculadopela internet tornouse objeto de novas correções e revisões atá alcançar a forma final.(AU)¼

Artrite séptica como complicação clínica em pacientes com doença reumatóide / Infectious arthritis as a clinic complication in patients with rheumatoid arthritis

A doença reumatóide (DRe) é uma patologia reumática inflamatória crônica, sistêmica, progressiva e de etiologia desconhecida. Complicações infecciosas são bem conhecidas nos pacientes com DRe e especial atenção tem sido dada aos processos infecciosos intra-articulares. O atraso no diagnóstico das pioartrites e na instituição terapêutica pode ocasionar graves sequelas articulares e, eventualmente, óbito. Os autores analisaram a incidência e as características clínicas das artrites sépticas no curso evolutivo de pacientes com DRe. Material e métodos - Foram revisados 97 prontuários de pacientes com DRe internados na enfermaria de Reumatologia no período de janeiro de 1993 a dezembro de 1997 e preenchidos protocolos com dados referentes a sexo, idade, tempo de doença, duração de internação, articulação comprometida, agentes etiológicos, doenças associadas e fármacos usados. Resultados - Dos 97 pacientes internados por DRe, cinco apresentavam artrite séptica como causa de internação. A idade média dos pacientes foi de 65 anos, o tempo médio de DRe foi de 12 anos e a duração média de internação nestes casos foi de 47,2 dias. As articulações acometidas foram: joelhos (três casos), quadril (um caso), ombro (um caso). O Staphylococcus aureus foi o agente etiológico mais frequente. Todos os pacientes estavam em uso de prednisona, com dose média de 6,5 mg/dia e um deles fazia uso de metotrexato (7,5mg/semana). conclusão - As artrites sépticas são causas de complicações em pacientes com DRe. O principal diagnóstico diferencial para os casos de artrite séptica deve ser com a exacerbação/reativação da própria DRe. Nesta casuística as pioartrites ocorreram em pacientes com doença de longa duração e/ou naqueles com idade avançada. Concordando com a literatura, o agente etiológico mais comum foi o Staphylococcus aureus e, a articulação mais acometida, o joelho. O rápido reconhecimento do quadro clínico e a instituição de tratamento adequado são fundamentais para a boa resolução do processo, sem que haja piora do quadro já estabelecido pela DRe