Prevalência e fatores associados a enteroparasitoses em pacientes com artrite reumatoide

Dissertação (mestrado) — Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, 2016.Introdução: Os pacientes portadores de doenças reumáticas apresentam profundas alterações no sistema imunitário em virtude das doenças de base e dos tratamentos utilizados, o que aumenta o risco de ocorrência e a gravidade de infecções, dentre elas as enteroparasitoses. O tratamento atual da artrite reumatoide envolve terapias imunossupressores potentes havendo a necessidade de rastreamento para processos infecciosos latentes. Não há na literatura estudos de prevalência de parasitoses em portadores de artrite reumatoide até o momento. O conhecimento destes dados epidemiológicos são fundamentais para fornecer elementos para o adequado manejo destes pacientes na prática clínica. Objetivos: a) Avaliar a prevalência de parasitoses em uma população com Artrite Reumatoide; b) Determinar a prevalência das helmintíases e protozooses por espécie nos pacientes; c) Avaliar as condições socioeconômicas dos pacientes e sua relação com a ocorrência das enteroparasitoses; d) Demonstrar a possível relação entre a presença de parasitoses intestinais e parâmetros de atividade de doença. Pacientes e Métodos: Foram coletados dados socioeconômicos demográficos e clínicos de uma amostra de conveniência de 67 pacientes acompanhados regularmente no ambulatório de AR do Hospital Universitário de Brasília no período de julho de 2015 a abril de 2016. Todos os pacientes foram submetidos ao exames parasitológico de fezes (EPF) pelo método de Hoffman, Pons e Janer (HPJ). Foram obtidas as frequências das variáveis de interesse, realizada análise bivariada e análise de regressão de Poisson múltipla com variância robusta. Resultados: A idade média foi de 53.9 anos, com predomínio em mulheres (94%) brancas (47.8%). O tempo médio de doença foi de 9.2 anos e a maioria dos pacientes estava com a doença em remissão ou atividade leve . A prevalência de parasitoses foi de 11.9%, sendo todos os casos de protozoários das seguintes espécies: Endolimax nana, Entamoeba histolytica e Entamoeba Coli. A análise multivariada final indicou que a presença de parasitose tem relação estatística significativa com ausência fadiga pela EVA (p = 0,0488) e com melhor índice de saúde atual pela EVA (p = 0,0012).Introduction: Patients with rheumatic diseases have profound alterations in the immune system as a result of underlying diseases and the treatments used, which increases the risk of occurrence and severity of infections, among them the enteroparasitosis. The current treatment of rheumatoid arthritis involves immunosuppressive therapies powerfully needed for screening infectious processes. There are no studies in the literature on the prevalence of parasitic infections in patients with rheumatoid arthritis till date. The knowledge of these epidemiologic data are crucial to provide elements for the proper management of these patients in clinical practice. Objectives: a) To assess the prevalence of parasitic diseases in a population with Rheumatoid Arthritis; b) To determine the prevalence of helminthiasis and protozooses by species in patients; (c) Assess the socioeconomic conditions of the patients and its relationship with the occurrence of enteroparasitosis; (d) To demonstrate the possible relationship between the presence of intestinal parasitic infections and parameters of disease activity. Patients and methods: We collected demographic and socioeconomic data of a convenience sample of 67 patients followed up regularly at the clinic of the Hospital Universitário de Brasília in July 2015 period to April 2016. All patients were presented for parasitological examination of stools (EPF) by Hoffman, Pons and Janer (HPJ). We obtained the frequencies of the variables of interest, performed bivariate analysis and logistic regression, Poisson regression with robust variance. Results: The mean age was 53.9 years, predominantly in women (94%) white (47.8%). The mean disease duration was 9.2 years and most patients had the disease in remission or light activity. The prevalence of parasitic infections was 11.9%, with all cases of protozoa of the following species: Endolimax nana, Entamoeba histolytica and Entamoeba coli. The final multivariate analysis indicated that the presence of disease has significant statistical relationship with no fatigue by VAS (p=0.0488) and best current health index by VAS (p = 0.0012)

Perfil terapêutico de pacientes com artrite reumatoide no Brasil : estudo de vida real

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências Médicas, Programa de Pós-Graduação em Ciências Médicas, 2019.A artrite reumatoide (AR) é uma doença crônica, sistêmica, de etiologia autoimune, caracterizada principalmente pelo acometimento inflamatório das articulações sinoviais periféricas. O atraso no diagnóstico, bem como o controle inadequado do processo inflamatório, podem gerar destruição articular com perda da capacidade funcional e qualidade de vida dos pacientes. Nas últimas décadas houve grande avanço no tratamento, a partir do surgimento de fármacos com novos mecanismos de ação e do conceito de “tratamento com meta – treat to target” (T2T). Acredita-se que a ênfase no diagnóstico precoce e no controle rigoroso da atividade de doença, com o uso racional do arsenal terapêutico atualmente disponível, estão associados com uma melhor evolução e prognóstico. Apesar do conceito teórico do T2T a sua implementação na prática clínica e seu consequente benefício ainda não estão bem estabelecidos, em especial em países da América Latina. No Brasil, os dados estatísticos a respeito do tratamento da AR são escassos e desta forma as informações de “vida real” são fundamentais tanto para o conhecimento dos médicos bem como no embasamento de políticas públicas de saúde. O objetivo principal deste estudo foi descrever os padrões de tratamento de pacientes brasileiros com artrite reumatoide no SUS. Metodologia: Este trabalho é um corte transversal do estudo REAL (“Artrite reumatoide na vida real no Brasil”), estudo multicêntrico com participação de 11 serviços públicos de reumatologia de diferentes estados brasileiros: UnB, UERJ, UNICAMP, USP, USP- Ribeirão Preto, UFPA, UFRGS, UFSC, UF Paraná, UFMG, HSPE-SP. Os pacientes foram submetidos a avaliação clínica, análise de exames complementares e do prontuário médico. Todos os dados coletados de cada centro foram incluídos em prontuário eletrônico desenvolvido especialmente para a pesquisa (“Meconsulte”) e acessado em tempo real, por meio de um tablet. Na análise estatística as variáveis contínuas foram comparadas utilizando o teste t de Student ou teste de Mann-Whitney. Para se comparar as proporções de pacientes das variáveis demográficas e clínicas entre grupos de medicação foi empregado o teste de qui-quadrado ou exato de Fisher. Resultados: Foram analisados 1125 pacientes sendo 89.5% mulheres com mediana de idade de 56.6 anos e tempo de doença de 152.5 meses. 78.73% eram fator reumatoide positivo e 55.2% tinham doença erosiva. A mediana do DAS foi de 3.52. Em relação ao tratamento verificamos que 529 (47,2%) usavam corticoides, 122 (10.9%) estavam em uso de antiinflamatórios não esteroidais (AINES), 1022 (90,84%) medicamentos modificadores do curso da doença (MMCD) sintético convencional (MMCDsc) e 406 (36.09%) MMCD biológico (MMCDb) . O metotrexato (MTX) foi o medicamento mais utilizado (66,49%) seguido de leflunomida (33.87%). (142/ 12.6%) utilizavam a associação MTX + leflunomida e apenas 0.44% da população estava em uso de MTX + hidroxicloroquina + sulfassalazina. A maioria dos pacientes analisados neste estudo estava usando MMCDsc por períodos prolongados e o MTX apresentou maior duração de uso. Índices de interrupção devido à ineficácia e efeitos colaterais dos MMCD sintéticos e biológicos também foram analisados. Conclusão: Particularidades foram vistas neste primeiro estudo multicêntrico de vida real no Brasil: uso elevado de corticoides, baixo uso de AINE, uso significativo da associação MTX + leflunomida (esquema pouco utilizado em outros países) e baixíssima frequência do esquema tríplice (MTX + hidroxicloroquina + sulfassalazina). As informações obtidas a respeito do tratamento da AR no Brasil são extremamente importantes para melhor compreensão do assunto e gerenciamento de recursos.Introduction: Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune etiology characterized mainly by the inflammatory involvement of the peripheral synovial joints. Delayed diagnosis, as well as inadequate control of the inflammatory process, can lead to joint destruction with loss of functional capacity and quality of life of the patients. In the last decades, there has been a great advance in the treatment, from the emergence of drugs with new mechanisms of action and the concept of "treatment with meta - treat to target" (T2T). It is believed that the emphasis on early diagnosis and strict control of disease activity, with the rational use of the currently available therapeutic arsenal, are associated with improved outcome and prognosis. Despite the theoretical concept of T2T its implementation in clinical practice and its consequent benefit are still not well established, especially in Latin American countries. In Brazil, statistical data regarding the treatment of RA are scarce and thus "real life" information is fundamental both for the knowledge of physicians as well as on the basis of public health policies. The main objective of this study was to describe the treatment patterns of Brazilian patients with rheumatoid arthritis in SUS. Methodology: This is a cross-section of the REAL study ("Rheumatoid arthritis in real life in Brazil"), a multicenter study involving 11 public rheumatology services from different Brazilian states: UnB, UERJ, UNICAMP, USP, USP-Ribeirão Preto , UFPA, UFRGS, UFSC, UF Paraná, UFMG, HSPE-SP. The patients were submitted to clinical evaluation, analysis of complementary exams and medical records. All data collected from each center were included in an electronic medical record specially developed for the research ("Meconsulte") and accessed in real time through a tablet. In the statistical analysis, continuous variables were compared using Student's t-test or Mann-Whitney test. In order to compare the proportions of patients of the demographic and clinical variables between groups of medication, the chisquare or Fisher's exact test was used. Results: A total of 1125 patients were analyzed, 89.5% of whom were women with a median age of 56.6 years and a disease duration of 152.5 months. 78.73% were positive rheumatoid factor and 55.2% had erosive disease. The median of DAS was 3.52. Regarding treatment, 529 (47.2%) used corticosteroids, 122 (10.9%) were on non-steroidal anti-inflammatory drugs (NSAID), 1022 (90.84%) conventional synthetic disease modifying antirheumatic drugs (csDMARD) and 406 (36.09%) biological disease modifying antirheumatic drugs (bDMARD). Methotrexate (MTX) was the most used drug (66.49%) followed by leflunomide (33.87%). (142 / 12.6%) used the MTX + leflunomide combination and only 0.44% of the population was using MTX + hydroxychloroquine + sulfasalazine. Most of the patients analyzed in this study were using csDMARD for prolonged periods and MTX presented longer duration of use. Interruption indices due to ineffectiveness and side effects of synthetic and biological DMARD were also analyzed. Conclusion: Particularities were seen in this first multicenter real-life study in Brazil: high use of corticosteroids, low use of NSAID,significant use of the combination MTX + leflunomide (a scheme rarely used in other countries) and very low frequency of the triple scheme (MTX + hydroxychloroquine + sulfasalazine). The information obtained regarding the treatment of RA in Brazil is extremely important for a better understanding of the subject and the management of resources

Síndromes gripais e infecção por coronavírus em pacientes usuários de imunossupressores no DF: um estudo de caso controle

Em um contexto de pandemia pelo COVID-19 em que mais de 150 milhões de casos jáocorreram, busca-se avaliar o comportamento das síndromes gripais e do COVID-19 napopulação com doenças reumatológicas em uso de imunossupressores convencionaissintéticos no Distrito Federal. Por meio de um questionário aplicado em entrevistastelefônicas, os pacientes foram acompanhados durante 12 semanas em 5 contatos paraavaliar a presença de sintomas gripais ou casos confirmados de COVID-19. Os dados coletadosforam analisados descritivamente, feitas associações entre duas variáveis categóricasutilizando-se os testes de Qui-Quadrado e teste exato de Fisher, e realizadas comparações demédias entre dois grupos por meio de testes não paramétricos de Mann-Whitney e de Kruskal-Wallis. Foram estimadas regressões Binomiais Negativas simples (univariada) e múltiplas(multivariada). Para todos os testes estatísticos foram utilizados um nível de significância de5%. As análises estatísticas foram realizadas com o uso do software estatístico SPSS 20.0 eSTATA 12. Um total de 373 pacientes foram incluídos no estudo, 170 faziam uso deimunossupressores, a maioria era do sexo feminino (91,7%, n=342) com a média de idade de45,7 anos. Em relação às comorbidades no grupo em uso de imunossupressores 20% (n=33)tinham hipertensão arterial sistêmica, 11,5% (n=19) tinham doença renal, 7,3% (n=12) tinhamdoença pulmonar, 6,1% (n=10) tinham cardiopatia e 5,5% (n=9) tinham diabetes mellitus. Nomodelo multivariado final a idade (p=0,001) e uso de imunossupressor (p=0,003) foramsignificativas. Observou-se que a frequência de sintomas gripais foi 66,0% maior em pacientesque faziam uso de imunossupressores comparativamente àqueles que não faziam uso dessamedicação. Não se obteve diferença significativa no número de casos por COVID-19. Dessaforma, o uso de imunossupressores convencionais sintéticos associou-se a uma maiorfrequência de sintomas gripais

Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs

A Brazilian cohort of patients with immuno-mediated chronic inflammatory diseases infected by SARS-CoV-2 (ReumaCoV-Brasil Registry) : protocol for a prospective, observational study

Background: Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, several questions were raised regarding the impact of COVID-19 at the start of the pandemic. Objective: This paper presents the protocol of a study that aims to prospectively evaluate patients with IMRD and a confirmed COVID-19 diagnosis (using criteria provided by the Brazilian Ministry of Health). Methods: The study comprised a prospective, observational cohort (patients with IMRD and COVID-19) and a comparison group (patients with only IMRD), with a follow-up time of 6 months to evaluate differences in health outcomes. The primary outcomes will be changes in IMRD disease activity after SARS-CoV-2 infection at 4 time points: (1) at baseline, (2) within 4-6 weeks after infection, (3) at 3 months after the second assessment (±15 days), and (4) at 6 months (±15 days). The secondary outcomes will be the progression rate to moderate or severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death, and therapeutic changes related to IMRD. Two outcomes—pulmonary and thromboembolic events in patients with both IMRD and SARS-CoV-2 infection—are of particular interest and will be monitored with close attention (clinical, laboratory, and function tests as well as imaging). Results: Recruitment opened in May 2020, with 1300 participants recruited from 43 sites as of November 2020. Patient recruitment will conclude by the end of December 2020, with follow-up occurring until April 2021. Data analysis is scheduled to start after all inclusion data have been collected, with an aim to publish a peer-reviewed paper in December 2020. Conclusions: We believe this study will provide clinically relevant data on the general impact of COVID-19 on patients with IMRD

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

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

High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID-19 : first results of ReumaCoV Brasil registry

Objectives To evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19. Methods Analysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study. Results 334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p<0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p<0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p<0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p<0.018). Conclusions Age >50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process

Predictors of serious infections in rheumatoid arthritis—a prospective Brazilian cohort

Abstract Background Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. Objective To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. Methods We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. Results 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5–6.9), 3.6 times (95% CI: 1.2–10.4) and 2.4 times (95% CI: 1.2–5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3–12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20–120%). Conclusion The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort