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. (RA therefore minimized Brazil ACREULAR ACR EULAR 2010 (2010 assessed opportunity 6 1 MannKendall Mann Kendall test chisquared chi squared Cramers Cramer s conducted 111 894 89 4 89.4 female 568 56 56.8 white SD (SD 571 57 57. 11.5 115 5 (11.5 tau 0677 0 677 0.677 0.001 0001 001 0695 695 0.695 199 2015 period , 3- 6- 12month month 0120 120 0.120 0200 200 0.20 0261 261 0.261 respectively. respectively . respectively) improvements 2011–2015 20112015 2011 (2011–2015 median IQR (IQR) 4–12 412 (4–12 5–17 517 17 (5–17 respectively, respectively] 172 2 17.2 shortest 3month window ≥ ( ≤ months. 201 (201 89. 56. 11. (11. 067 67 0.67 0.00 000 00 069 69 0.69 19 012 0.12 020 20 0.2 026 26 0.26 2011–201 2011201 (2011–201 (IQR 4–1 41 (4–1 5–1 51 (5–1 17. (20 (11 06 0.6 0.0 01 0.1 02 0. 2011–20 201120 (2011–20 4– (4– 5– (5– (2 (1 2011–2 20112 (2011–2 (4 (5 2011– (2011– (2011

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. (RA reallife real life settings care longterm term conditions ACREULAR ACR EULAR 2010 (2010 1987 (1987 conducted “early “late afterwards inquired DAS28CRP DASCRP DAS28 CRP DAS (DAS28-CRP HAQDI HAQ DI (HAQ-DI Students Student s t MannWhitney Mann Whitney U chisquared chi squared tests analysis scorematched score vs lateassessed assessed approval consent 105 89.4% 894 89 4 (89.4 female 565 56 5 56.5 white white) SD (SD age 569 9 56. 11.5 115 11 (11.5 years duration 1731 173 1 173. 114.5 1145 114 (114.5 IQR (IQR coincided 6–36 636 36 (6–36 64.6% 646 64 (64.6% practitioner Notwithstanding 807 80 7 80.7 28.7% 287 28 (28.7% ≤ ( symptoms. . symptoms) rho 0.816 0816 0 816 0.001. 0001 0.001 001 0.001) OR 2.77 277 2 77 95 CI 193 93 1.93 3.97. 397 3.97 3 97 3.97) remissionlow remission low 0.74 074 74 055 55 0.55 0.99, 099 0.99 , 99 0.99) earlyassessed difference [95 CI] 025 25 −0.2 −0.46, 046 46 [−0.46 −0.04 004 04 0196 196 0.19 −0.306, 0306 306 [−0.306 −0.087 0087 087 respectively. respectively respectively) propensityscore whole (whole sample 201 (201 198 (198 DAS2 10 89.4 8 (89. 11. (11. 17 114. (114. 6–3 63 (6–3 64.6 (64.6 80. 28.7 (28.7 0.81 081 81 000 0.00 00 2.7 27 19 1.9 39 3.9 0.7 07 05 0.5 09 0.9 [9 02 −0. −0.46 [−0.4 −0.0 019 0.1 −0.306 030 30 [−0.30 −0.08 008 08 20 (20 (19 89. (89 (11 (114 6– (6– 64. (64. 28. (28. 0.8 0.0 2. 1. 3. 0. [ −0 −0.4 [−0. 01 −0.30 03 [−0.3 (2 (1 (8 (6 (64 (28 [−0 −0.3 [−

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.

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.

Abstract Background: There are few data on the epidemiology, clinical manifestations and management of RA in Brazil, even with the recognition of the high direct, indirect and societal costs of this disease. Herein, we report the formation of the REAL - Rheumatoid Arthritis in Real Life, the first nationally representative multicenter prospective observational study in Brazil. Methods: The REAL study was designed to include a total of 1300 evaluable patients from 13 tertiary care public health centers specialized in RA management and representative of 5 regions of Brazil. Each center was expected to enroll ~ 100 consecutively seen patients and follow them prospectively in a systematic protocol-driven fashion with scheduled visits at baseline, 6 and 12 months. Core clinical, laboratory and patient-reported outcomes measures were required to be collected at each visit. Results: A total of 1115 patients (89.4% female, mean age of 56.7 years and median disease duration of 12.7 years) were enrolled from 11 participating centers. Almost 80% of patients were of middle-low or low socioeconomic classes. The median educational time was 8 years, with 3.23% being below literacy level. The interval between symptoms and diagnosis varied from 1 to 457 months (median 12 months). Almost half of the patients were on glucocorticoids, 96.5% on DMARDs, with 35.7% on biologics. Median HAQ-DI was 0.875, ranging from 0 to 3. Median DAS28-ESR was 3.5, with 58.7% of patients presenting moderate or high disease activity. Conclusions: The first large cohort of Brazilian patients with RA in a real-life setting shows several striking differences from previously published cohorts from other countries. The long delay for diagnosis and start of DMARDs may partly explain the high frequency of erosive disease. An elevated percentage of patients on moderate or high disease activity was seen, despite of the high frequency of corticosteroid and biologics utilization. Data from this cohort may enable public health managers of developing countries better allocate the limited resources available for the care of RA patients.

Objetivo: Avaliar o escore US7 modificado (escore MUS7 SIN) na avaliação de pacientes com artrite reumatoide inicial (ARI). Além disso, foram examinados recessos dorsais e palmares dos punhos, bem como pequenas articulações das mãos e dos pés, para o diagnóstico de sinovite, mediante uma avaliação global das articulações. Métodos: A amostra do estudo compreendeu 32 pacientes tratados para artrite, com 13 meses como duração média da doença. Foi utilizado um aparelho de ultrassonografia (US) com transdutor de alta frequência. As mãos dos participantes também foram radiografadas e analisadas pelo escore de Larsen. Resultados: Nas 832 articulações examinadas, detectou-se sinovite em 173 (20,79%), tenossinovite em 22 (4,91%) e erosões em três (1,56%). A sinovite foi predominantemente detectada no recesso dorsal (73,38%) das articulações MCF e IFP, quando comparado com o recesso palmar (26%). A presença de sinovite nas articulações avaliadas teve correlação com os resultados clínicos (HAQ-DI, DAS28), laboratoriais (anti-PCC, FR, PCR) e ultrassonográficos (r = 0,37 a r = 0,42; p = 0,04 a p = 0,003). Encontramos correlação do escore MUS7 SIN para US na técnica da escala de cinzas (gray scale) ou na técnica de Doppler de amplitude (power Doppler) com os valores do instrumento DAS28 (PCR) (r = 0,38; p = 0,0332) e com os resultados da PCR (r = 0,39; p = 0,0280), respectivamente. Conclusão: O recesso dorsal, o punho e as pequenas articulações podem ser considerados como locais importantes para a detecção de sinovite pelo escore MUS7 SIN em pacientes com ARI.

Objective: To evaluate the modified US7 score (MUS7 score SYN) in the assessment of patients with early rheumatoid arthritis (ERA). In addition, dorsal and palmar recesses of the wrists as well as of small joints of the hands and feet were examined for the presence of synovitis by means of a global assessment of joints. Methods: The study sample comprised 32 patients treated for arthritis, with an average disease duration of 13 months. An ultrasound machine with high frequency transducer was used. Hands were also X-rayed and analysed by Larsen score. Results: Out of the 832 examined joints, synovitis was detected in 173 (20,79%), tenosynovitis in 22 (4,91%), and erosions in 3 (1,56%). Synovitis was predominantly detected in the dorsal recess (73,38%) of MCP and PIP joints, when compared with palmar recess (26%). The presence of synovitis in the joints evaluated correlated with clinical (HAQ-DI, DAS28), laboratory (ACPA, RF, CRP), and ultrasound results (r = 0,37 to r = 0,42; p = 0,04 to p = 0,003). We found correlation of the MUS7 score SYN of the gray scale US or of the power Doppler US with DAS28 (PCR) values (r = 0,38; p = 0,0332), and with CRP results (r = 0,39; p = 0,0280), respectively. Conclusion: The dorsal recess, the wrist, and small joints can be considered as important sites to detect synovitis by the MUS7 score SYN in patients with ERA.

Os bisfosfonatos são potentes inibidores da reabsorção óssea e são utilizados no tratamento da osteoporose e de outras doenças que causam a perda de massa óssea, como doença de Paget, metástases ósseas e mieloma múltiplo, prevenindo fraturas patológicas. Desde 2003, estudos associam osteonecrose avascular dos ossos maxilares a seu uso, principalmente intravenoso. Na literatura, há relatos de ocorrência variando de 0,8% a 12%, dos pacientes, na sua maioria em uso prolongado. Médicos e dentistas devem estar cientes dessa potencial complicação no tratamento odontológico.

Bisphosphonates are potent inhibitors of bone resorption, and are used in the treatment of osteoporosis and other diseases that cause bone mass loss, such as Paget's disease, bone metastases, and multiple myeloma, to prevent pathological fractures. Since 2003, avascular osteonecrosis of the jaw has been associated with the use of bisphosphonates, mainly intravenous. According to the literature, the occurrence of osteonecrosis of the jaw has ranged from 0.8% to 12% of the patients on bisphosphonates, most of them on prolonged use. Physicians and odontologists should be aware of that potential complication in dental treatment.

OBJETIVO: Determinar a prevalência de sintomas depressivos e ansiosos na artrite reumatóide (doença inflamatória crônica) em comparação com um grupo controle com osteoartrite (doença crônico-degenerativa não inflamatória). Identificar variáveis sociodemográficas e clínicas associadas a sintomas depressivos nesses pacientes. MÉTODO: Participaram do estudo 62 pacientes com artrite reumatóide e 60 pacientes com osteoartrite. Foram coletados dados sociodemográficos e clínicos e foram aplicadas as escalas Hospital Anxiety and Depression Scale e Disability Index of the Health Assessment Questionnaire. RESULTADOS: A prevalência dos sintomas depressivos foi 53,2% na artrite reumatóide e 28,3% na osteoartrite (p = 0,005). A prevalência dos sintomas ansiosos foi 48,4% na artrite reumatóide e 50,0% na osteoartrite (p = 0,859). Os valores médios (desvio padrão) de Disability Index of the Health Assessment Questionnaire foram 1,4 (0,8) na artrite reumatóide e 1,4 (0,6) na osteoartrite (p = 0,864). Pacientes com artrite reumatóide e sintomas depressivos apresentaram menor nível educacional e maiores níveis de atividade da doença e incapacidade funcional. CONCLUSÃO: Embora ambas as doenças reumatológicas sejam similares em termos de dor e incapacidade funcional, uma prevalência significativamente maior de sintomas depressivos na artrite reumatóide foi encontrada. Essa diferença poderia ser explicada por meio da hipótese de um mecanismo neuroimunobiológico relacionado às citocinas nas doenças inflamatórias, o qual vem sendo considerado candidato para o desenvolvimento de sintomas depressivos.

OBJECTIVE: To determine the prevalence of depressive and anxiety symptoms in patients with rheumatoid arthritis (a chronic inflammatory disease) in comparison to a control group with osteoarthritis (a chronic non-inflammatory degenerative disease) and to identify the sociodemographic and clinical variables associated with depressive symptoms in these patients. METHOD: Sixty-two rheumatoid arthritis patients and 60 osteoarthritis patients participated in the study. Sociodemographic and clinical data were collected and the Hospital Anxiety and Depression Scale and the Disability Index of the Health Assessment Questionnaire were applied. RESULTS: The prevalence of depressive symptoms was of 53.2% in rheumatoid arthritis and 28.3% in osteoarthritis (p = 0.005). The prevalence of anxiety symptoms was of 48.4% in rheumatoid arthritis and 50.0% in osteoarthritis (p = 0.859). The mean (and standard deviation) scores in the Disability Index of the Health Assessment Questionnaire were 1.4 (0.8) in rheumatoid arthritis and 1.4 (0.6) in osteoarthritis (p = 0.864). Rheumatoid arthritis patients with depressive symptoms had lower education and higher disease activity and functional disability. CONCLUSION: Although these two rheumatic diseases are similar in terms of the pain and functional disability that they cause, a significantly higher prevalence of depressive symptoms was found in rheumatoid arthritis patients. This difference might be explained by the hypothesis of a neuroimmunobiological mechanism related to cytokines in inflammatory diseases, which has been considered as a candidate to the development of depressive symptoms.

Apesar de rara, a pneumoconiose reumatoide, também chamada de síndrome de Caplan, pode ser diagnosticada entre trabalhadores expostos à sílica e entre pacientes com silicose, pneumoconiose dos mineiros de carvão e asbestose. A maior prevalência ocorre entre os silicóticos, apesar de ter sido descrita inicialmente em mineiros de carvão com pneumoconiose. O achado que define o tipo clássico da síndrome é a presença de nódulos reumatoides nos pulmões, independente da presença ou não de pequenas opacidades pneumoconióticas, ou de grandes opacidades de fibrose pulmonar maciça, associada ou não a um quadro de artrite reumatoide em atividade. Relatamos o caso de uma mulher com quadro de artrite reumatoide, diagnosticada 34 anos após exposição à sílica livre em uma indústria de porcelana por 7 anos, apresentando radiograma de tórax com opacidades arredondadas de 1 a 5 cm de diâmetro, distribuídas na periferia de ambos os pulmões. A biópsia transtorácica guiada por TC de um dos nódulos revelou tratar-se de nódulo reumatoide com macrófagos em paliçada, típico da síndrome de Caplan. São discutidos aspectos de diagnóstico da síndrome, classificação e ocorrência, ressaltando a importância da anamnese ocupacional em casos de artrite reumatoide com opacidades radiológicas pulmonares.

Although rare, rheumatoid pneumoconiosis, also known as Caplan's syndrome, can occur in workers exposed to silica, as well as in patients with silicosis, coal workers' pneumoconiosis or asbestosis. Prevalence is higher among patients with silicosis, despite the fact that it was originally described in coal workers with pneumoconiosis. The classical finding that defines this syndrome is that of rheumatoid nodules in the lungs, regardless of whether there are small rounded opacities suggestive of pneumoconiosis or large opacities consistent with massive pulmonary fibrosis, with or without clinical rheumatoid arthritis. We describe the case of a female patient with rheumatoid arthritis, diagnosed 34 years after 7 years of occupational exposure to silica at a porcelain plant. A chest X-ray showed circular opacities of 1-5 cm in diameter, bilaterally distributed at the periphery of the lungs. A CT-guided thoracic punch biopsy of one of those nodules revealed that it was rheumatoid nodule surrounded by a palisade of macrophages, which is typical of Caplan's syndrome. Aspects of diagnosis, classification and occurrence of this syndrome are discussed, emphasizing the importance of the occupational anamnesis of patients with rheumatoid arthritis and lung opacities on chest X-rays.

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. 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.