Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01–1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29–3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

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.

Abstract Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA. Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database. Results: The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06–20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09–138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10–0.67, P < 0.005). Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA. Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.

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 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 Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.

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.

Resumo Introdução: Os tratamentos para artrite reumatoide (AR) e osteoartrite (OA) devem diminuir dor, modular inflamação e diminuir deformidades. O LLLT é um biomodulador e pode auxiliar no quadro clínico destas. Objetivo: Analisar os parâmetros mais comumente utilizados para a diminuição das respostas de dor em pacientes com AR e OA em ensaios clínicos controlados e não controlados. Método: Trata-se de uma revisão sistemática com busca de artigos em inglês, português e espanhol na: PUBMED, SCOPUS, LILACS e Web of SCIENCE, entre 2006 a 2018. Foram utilizados os descritores MESH. Critérios de inclusão: avaliação da eficácia do LLLT nestas populações, verificação da dor antes e depois do tratamento, ensaios clínicos controlados e não controlados, publicados integralmente. Foi realizado o cálculo da dosimetria do laser e análise de média, mediana e moda da energia por ponto e energia por tratamento. Resultados: Incluídos neste estudo 3 artigos de AR e 16 de OA. Em relação à dosimetria, apenas um AR apresentou redução da dor, sendo este com a maior dose de energia. Já na OA, a maioria dos artigos apresentou diminuição da dor, e com variabilidade na dosagem aplicada. Alguns tiveram poucos parâmetros apresentados, tornando impossível calcular a dosimetria. Conclusão: há evidências científicas para reduzir a dor relatada em pacientes com OA de joelho, principalmente com doses de 6 J por ponto e 48 J aplicadas no tratamento diário. Para as outras articulações afetadas com OA e AR, seria importante a publicação de mais artigos científicos com melhor qualidade metodológica e descrição da dosimetria.

Abstract Introduction: Treatments for rheumatoid arthritis (RA) and osteoarthritis (OA) can reduce, modulate inflammation, and reduce deformities. Low-Level Laser Therapy is a biomodulator and may aid in the clinical picture of these conditions. Objective: To analyze the parameters most frequently used to determine the responses of patients with RA and OA in controlled and uncontrolled clinical trials. Method: This is a systematic review with search of articles in English, Portuguese and Spanish in PUBMED, SCOPUS, LILACS and Web of SCIENCE, of articles published between 2006 and 2018. MeSH terms were used. Inclusion criteria: evaluation of LLLT in the evaluations, evaluation and evaluation of the period, controlled and uncontrolled clinical trials, full publications. The base date of the energy dosimetry and the analysis of mean, median and mode of energy per point and energy per treatment. Results: Three articles on RA and 16 on OA were included in this study. Regarding dosimetry, it was one of the most recent of the pain, being this one with a greater energy dose. In OA, most of the articles presented are of importance, with variability in the dosage applied. Conclusion: There are several reports for patient studies purposes, mainly with doses of 6 J per point and 48 J. In the joints affected with OA and AR, it would be important to publish more scientific articles with better methodological quality and description of dosimetry.

Resumen Introducción: Los tratamientos para la artritis reumatoide (AR) y la osteoartritis (OA) pueden reducirse, modular, encender y disminuir las deformidades. El LLLT es un biomodulador y puede auxiliar en el cuadro clínico de éstas. Objetivo: Analizar los parámetros más frecuentemente utilizados para determinar las respuestas de pacientes con AR y OA en ensayos clínicos controlados y no controlados. Método: Se trata de una revisión sistemática y la búsqueda de artículos en Inglés, portugués y español en: PubMed, SCOPUS, se utilizaron LILACS y Web of Science, entre 2006 y 2018. Los descriptores de malla. Criterios de inclusión: evaluación de la LLLT en las evaluaciones, evaluación y evaluación del período, ensayos clínicos controlados y no controlados, íntegramente. La fecha base de la dosimetría de energía y el análisis de media, media y moda de la energía por punto y energía por tratamiento. Resultados: Incluido en este estudio 3 artículos de AR y 16 de OA. En cuanto a la dosimetría, fue uno de los más recientes del dolor, siendo éste con una dosis mayor de energía. En la OA, la mayoría de los artículos presentados son de importancia, con la variabilidad en la dosificación aplicada. Se han tenido pocos pocos parámetros parámetros parámetros presentados presentados. Conclusión: hay una serie de informes para fines de estudios con pacientes, principalmente con dosis de 6 J por punto y 48 J. Las articulaciones afectadas con OA y AR, sería importante la publicación de más artículos científicos con mejor calidad metodológica y descripción de dosimetría.

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.

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.

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.

Objetivo: Avaliar a distribuição dos reumatologistas no Brasil e sua correlação com oferta de residência médica (RM) especializada, Produto Interno Bruto (PIB) e Índice De Desenvolvimento Humano Municipal (IDH-M) das unidades da federação (UFs). Métodos: Consulta a várias bases de dados oficiais, sumarização de dados por técnicas estatísticas descritivas e cruzamento de informações. Para análise de correlação, utilizou-se o coeficiente de Spearman (r). Resultados: Foram encontrados 1.229 reumatologistas registrados regularmente no país. A região Norte reunia apenas 3,6% desse contingente (n = 44), enquanto o Sudeste, 42,2% (n = 519). As capitais somadas aos cinco maiores municípios de cada UF concentraram 75,8% desses especialistas (n = 931). No total, 49,9% dos reumatologistas prestavam atendimento pelo Sistema Único de Saúde (SUS). Achou-se razão geral de 157.809 habitantes para cada reumatologista no Brasil, porém com grande variação entre as UF quanto a essa proporção. Entre 2000 e 2012, houve 593 concluintes de RM em reumatologia no Brasil. Achou-se correlação positiva do número de reumatologistas ante o PIB (r = 0,94), o IDH-M da capital (r = 0,77) e o número de concluintes de RM em reumatologia (r = 0,79) das UF. Conclusões: Observou-se forte concentração de reumatologistas nas capitais e maiores municípios brasileiros, com inequalidades perceptíveis também entre as UF e as regiões do país. A distribuição desses profissionais acompanhou o PIB, o IDH-M da capital e o número de concluintes de RM em reumatologia das UF, sugerindo que fatores relacionados a oportunidades de renda e desenvolvimento humano e ao local de formação especializada podem influir na fixação geográfica dos reumatologistas.

Objective: To assess the distribution of rheumatologists in Brazil and their correlation with Medical Residency specialization offer, Gross Domestic Product (Gdp) And Municipal Human Development Index (HDI-M) of units of the federation (UFs). Methods: Query to various official databases, data summarization by techniques for descriptive statistics and cross-referenced information. For correlation analysis, we used the Spearman correlation coefficient (r). Results: There were 1229 rheumatologists regularly registered in the country. The Northern region had only 3.6% of the total (n = 44), while the Southeast had 42.2% (n = 519). The State capitals, added to the five largest municipalities in each UF, concentrated 75.8% of these specialists (n = 931). In total, 49.9% of rheumatologists offered treatment at SUS. A general ratio of 157,809 inhabitants per rheumatologist in Brazil was determined, but with wide variation among UFs with respect to this ratio. In the years 2000-2012, there were 593 Rheumatology Residency graduated physicians in Brazil. We observed a positive correlation among number of rheumatologists compared with GDP (r = 0.94), HDI-M of the State capitals (r = 0.77) and number of Rheumatology Residency graduated physicians (r = 0.79) in UFs. Conclusions: We noted a strong concentration of rheumatologists in State capitals and larger municipalities, with noticeable inequalities also between UFs and country regions. The distribution of these professionals accompanied GDP, HDI-M of the State capital and number of Rheumatology Residency graduated physicians, suggesting that factors related to income opportunities and human development and the place of speciality training may influence the geographical fixation of rheumatologists.