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To investigate the association between periconceptional environmental exposures and the occurrence of cleft lips and palates.This case-control study analyzed 150 mothers of children with cleft lips and palates living in the same city as 250 mothers whose children did not present with this malformation (controls). Environmental exposure data were gathered through a questionnaire (Latin American Collaborative Study of Congenital Malformations methodology).Multivariate analysis revealed that monthly income below minimum wage, having another malformed child, other diseases in the first gestational trimester (urinary infection), use of pesticides in home gardens, and pesticide use in farms close to the home were risk factors associated with the malformation, whereas taking vitamins was a protective factor.Maternal and paternal exposure to pesticides is associated with cleft lip and palate in Mato Grosso State, Brazil.

Pesquisa desenvolvida com o objetivo de caracterizar o perfil sociodemográfico e antropológico das vítimas fatais de intoxicação por agrotóxicos, necropsiadas no IML de Cuiabá nos anos de 2010 a 2017, correlacionando a existência de subnotificação dos casos e o uso excessivo dos agrotóxicos no Estado de Mato Grosso. Foram analisados 32 laudos de necropsia e seus respectivos exames toxicológicos. Os resultados mostram que não houve diferença em relação ao sexo e que a faixa etária entre os 20 a 49 anos foi a mais acometida (71,88%). Foi maior o número de intoxicações em solteiros (65,63%), pardos (56,25%) e profissionais do Lar (18,75%). A via digestiva (71,88%) foi responsável pelo maior número de intoxicações. Maioria dos óbitos foi de causa suicida (43,75%), seguidos por acidental (12,50%) e homicida (6,25%). O trabalho agrícola não foi apontado, neste estudo, como fator determinante para morte por intoxicações. Os agrotóxicos da classe dos inseticidas foram identificados em 15,64% das amostras. Cerca de 84,38% das vítimas, receberam atendimento médico prévio ao óbito. Os resultados encontrados no estudo podem contribuir como instrumento norteador às questões relacionadas ao planejamento das ações em saúde frente à utilização dos agrotóxicos, principalmente, com o objetivo de restringir o acesso indiscriminado a estes venenos. Palavras-chave: Agrotóxico. Intoxicação. Óbito. Abstract Research developed with the aim of characterizing the socio-demographic and anthropological profile of fatal victims of pesticide poisoning, necropsied at the IML in Cuiabá in the years from 2010 to 2017, correlating the existence of underreporting of cases and the overuse of pesticides in the state of Mato Grosso. 32 necropsy reports and their respective toxicological exams were analyzed. The results show that there was no difference in relation to sex and that the age group between 20 to 49 years was the most affected (71.88%). There was a greater number of intoxications in single (65.63%), brown (56.25%) and home professionals (18.75%). The digestive tract (71.88%) was responsible for the largest number of intoxications. Most deaths were suicidal (43.75%), followed by accidental (12.50%) and homicidal (6.25%). Agricultural work was not identified in this study as a determining factor for poisoning death. Pesticides of the insecticide class were identified in 15.64% of the samples. About 84.38% of the victims received medical care prior to death. The results found in the study can contribute as a guiding instrument to issues related to the planning of health actions regarding the use of pesticides, mainly with the objective of restricting indiscriminate access to such poisons. Keywords: Pesticide. Intoxication. Death.

A artrite reumatoide é uma doença inflamatória, crônica, autoimune, sistêmica e progressiva com etiologia ainda desconhecida, que causa danos progressivos ao sistema musculoesquelético. Esta doença atinge aproximadamente 0,5% a 1% da população mundial, predomina no sexo feminino e acomete todas as faixas etárias com maior prevalência entre 40-60 anos. A atividade da doença é avaliada pelo Índice de Atividade da Doença (DAS28) analisando 28 articulações. Estudos demonstram que a poluição atmosférica está associada aos agravos à saúde humana e à perda de qualidade de vida. Este estudo teve como objetivo relatar o papel da poluição atmosférica na artrite reumatoide, através de uma revisão narrativa de literatura, a partir das bases de dados PubMed e Scielo. Incluíram-se artigos nos idiomas inglês e português publicados em periódicos, nacionais e internacionais, acerca da temática da pesquisa. A relação entre o desenvolvimento da AR e diferentes poluentes atmosféricos foi analisada em diversos estudos, que demostraram associação entre diferentes poluentes atmosféricos e o desenvolvimento da doença, no entanto, nenhum estudo publicado até a data atual, avaliou a relação com a exacerbação da atividade da doença. Palavras-chave: Artrite Reumatoide. Poluição do Ar. Doenças Autoimunes. Abstract Rheumatoid arthritis is an inflammatory, chronic, autoimmune, systemic and progressive disease with a still unknown etiology that causes progressive damage to the musculoskeletal system. This disease affects approximately 0.5% to 1% of the world population, predominates in females and affects all age groups with a higher prevalence between 40-60 years. The disease activity is assessed by the Disease Activity Index (DAS28) analyzing 28 joints. Studies show that air pollution is associated with damage to human health and loss of quality of life. This study aimed to report the role of air pollution in rheumatoid arthritis, through a literature narrative review, using the PubMed and Scielo databases. Articles in English and Portuguese published in national and international journals about the research theme were included. The relationship between the RA development and different air pollutants has been analyzed in several studies, which showed an association between different air pollutants and the development of the disease, however, no study published to date has evaluated the relationship with the disease activity exacerbation. Keywords: Rheumatoid Arthritis. Air Pollution. Autoimmune Diseases.

Em função da Pandemia pelo COVID-19, houve a necessidade de elaborar um guia com intuito de nortear as ações dos serviços em funcionamento, buscando a segurança para pacientes em tratamento para doenças autoimunes e equipe de saúde envolvidos na prestação da assistência, sem prejuízo ao controle clínico destas doenças. Elaborar um Plano de enfrentamento e recomendar diretrizes para os Serviços de Terapia Assistida. Foram pesquisadas publicações de saúde pública nacional e internacional, sociedades de especialidades médicas de áreas afins das doenças, que se utilizam de imunomoduladores parenterais para tratamento e publicações nas principais bases de dados virtuais relacionando COVID-19, doenças reumáticas e drogas imunobiológicas. Com base em revisão de dados atuais da literatura, recomendações das principais sociedades de especialidades médicas relacionadas ao tema e agências de saúde pública, foi possível elaborar um plano de contingência para que serviços de terapia assistida para tratamento de doenças autoimunes não sofressem um impacto negativo desnecessário durante a Pandemia de COVID-19, permitindo assim a continuidade de tratamento para pacientes que necessitam uso contínuo de medicações imunomoduladoras parenterais, evitando a piora clínica destes pacientes. Palavras-chave: COVID-19. Doenças Reumáticas. Serviço de Terapia Assistida. Abstract Due to the Covid-19 pandemic, there was a need to prepare a coping plan to guide the services actions in operation, seeking safety for patients undergoing treatment for autoimmune diseases and the health team involved in providing care, without harming to the clinical control of such diseases. To develop a coping plan and recommend guidelines for assisted therapy services. Publications from national and international public health agencies, societies of medical specialties from disease-related areas that use parenteral immunomodulators for treatment and publications in the main virtual databases relating Covid-19, rheumatic diseases and immunobiological drugs were searched. Based on a review of current literature data, recommendations from the main societies of medical specialties related to the theme and public health agencies, it was possible to develop a contingency plan so that assisted therapy services for the autoimmune diseases treatment would not undergo an unnecessary negative effect during the Covid-19 pandemic, thus allowing treatment continuity for patients who need continuous use of parenteral immunomodulatory medications, preventing the clinical worsening of these patients. Keywords: Covid-19. Rheumatic Diseases. Assisted Therapy Services

Objective: The study aimed to evaluate the influence of storage temperature on immunobiological efficacy and safety in autoimmune rheumatic disease treatment. Methods: This observational study included adult patients with autoimmune rheumatic diseases who used immunobiologicals stored at home and were followed up at the rheumatology outpatient clinic of the General University Hospital of Cuiabá, Mato Grosso, Brazil, in 2017/2018. Patients were evaluated regarding disease activity and occurrence of adverse events, and a household survey of the temperature of the storage environment of these drugs was conducted. Results: Sixty patients with a mean age of 50.4 years were evaluated. Of these, 39 patients (65%) stored their biological drugs outside the recommended temperature range. Storage of the immunobiological at the incorrect temperature was 76% higher among patients with moderate/high rheumatic disease activity (p=0.003). Conclusion: Most patients stored their immunobiologicals outside the temperature range recommended in the package insert, and there was an association between incorrect storage temperature and moderate/high autoimmune rheumatic disease activity.

As doenças reumáticas autoimunes, tais como: artrite reumatoide, espondilite anquilosante, artrite psoriásica são doenças inflamatórias crônicas, que provocam deformidades permanentes. O tratamento dessas patologias envolve o uso de medicamentos imunobiológicos, que se caracterizam por ser termolábeis e de uso parenteral, necessitando de cuidados com a armazenagem em temperatura recomendada para a manutenção de sua eficácia e segurança. Estudos observacionais vêm demonstrando que a maioria dos pacientes armazena seus medicamentos imunobiológicos fora da temperatura recomendada em bula, e houve associação entre temperatura incorreta do armazenamento destas drogas e moderada/alta atividade das doenças reumáticas autoimunes. Orientar aos pacientes os cuidados de transporte, de armazenagem e de conservação dos medicamentos imunobiológicos em domicílio, visando preservar a eficácia e segurança do tratamento. Foram pesquisadas publicações sobre o armazenamento domiciliar dos medicamentos biológicos nas bases de dados virtuais e manuais de conservação dos orgãos de regulamemtação de armazenagem de biomedicamentos, relacionando terapia biológica, armazenamento doméstico e doenças reumáticas. Com a revisão de literatura foi possível elaborar normas quanto ao cuidado no transporte, no armazenamento e na conservação dos medicamentos imunobiológicos, respeitando a realidade local. Com o acesso às normas de armazenamento e conservação dos medicamentos imunobiológicos, os pacientes obtiveram maior conhecimento e, assim, uma resposta mais eficaz, diminuindo também a chance de eventos adversos durante o seu tratamento. Palavras-chave: Terapia Biológica. Temperatura Ambiental. Doenças Reumáticas. Antirreumáticos. Armazenamento Doméstico. Abstract Autoimmune rheumatic diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis are chronic inflammatory diseases that cause permanent deformities. The treatment of these pathologies involves the use of immunobiological drugs that are characterized by being thermolabile and for parenteral use, requiring care with storage at the recommended temperature to maintain their effectiveness and safety. Observational studies have shown that most patients store their immunobiological drugs outside the recommended temperature in the medicine package insert, and there was an association between incorrect storage temperature of such drugs and moderate / high autoimmune rheumatic diseases activity. Objective: To guide patients in the care of transport, storage and preservation of immunobiological drugs at home in order to preserve the treatment effectiveness and safety. Methods: Publications on the home storage of biological medicines were searched in the virtual databases and manuals for the conservation of biomedical storage regulatory bodies, concerning biological therapy and home storage. Result: With the literature review, it was possible to elaborate rules regarding the care in the transport, storage and conservation of immunobiological drugs, respecting the local reality. Conclusions: With access to the rules for storage and conservation of immunobiological drugs, patients obtained greater knowledge and thus a more effective response, also decreasing the chance of adverse events during their treatment. Keywords: Biological Therapy. Temperature. Rheumatic Diseases. Antirheumatic Agents. Home Storage.

Background: Evidence suggests that DNA damage is implicated in the development of Systemic Lupus Erythematosus (SLE). Objective: Investigate the possible association of polymorphisms in the DNA repair genes XRCC1 and XRCC3 with SLE and its clinical and laboratory features. Methods: This is a case-control study comparing the polymorphisms in the DNA repair genes XRCC1 and XRCC3 in SLE patients and control individuals. Genotyping for DNA repair genes was performed by polymerase chain reaction-restriction fragment length polymorphism in 76 patients and 82 healthy control individuals. Results: Our data indicated that the genotype frequencies in patients with the XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms were similar to those observed in the control group (p > 0.05). However, the frequencies of the 399Gln allele (p = 0.023, OR = 0.58, 95% CI = 0.36–0.93) and 241Met allele (p = 0.0039, OR = 0.59, 95% CI = 0.36–0.98) were significantly lower in the patients than those in the control subjects. Conclusion: We demonstrated that 399Gln and 241Met alleles may play a protective role in SLE susceptibility.

Objective.To evaluate the safety of the methotrexate (MTX)–leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors (JAKi).Methods.Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons.Results.In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76–1.31, P = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36–0.88, P = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25–0.94, P = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16–0.65, P = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis.Conclusion.In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.

BACKGROUND The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases. OBJECTIVES The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs. METHODS BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI). RESULTS A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01-4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15-2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups. CONCLUSIONS In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Background: As Brazil is accountable for 33% of the tuberculosis (TB) burden in Americas, with an annual incidence of 33.5/100,000 in 2017[1], the occurrence of tuberculosis infection in patients with rheumatic diseases in use of biological therapy is a recurrent concern. Objectives: To assess incident TB among patients with rheumatic disease in use of biological therapy in a country with high incidence of TB. Methods: BiobadaBrasil is a multicentric prospective cohort study involving patients with rheumatic diseases who started the first biologic or a synthetic disease modifying anti-rheumatic drug (DMARD)[6]. This analysis includes patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) recruited from Jan 2009 to Aug 2018 and followed-up for one or multiple courses of treatment until censoring or incident TB. The primary outcome was the incidence of tuberculosis (in any organ site). The history of exposure to tuberculosis, chest Rx, screening and treatment for latent tuberculosis infection (LBTI), and use of prophylactic isoniazid were evaluated before each course of treatment. Multivariate Cox proportional hazards models (with DMARDs included as time-varying covariates) were used to estimate hazard ratios (HR) and 95% confidence intervals (CI); analyses were performed with the Survival package of R. Results: Sample: 2858 patients (female =70,2%; RA = 72%, AS=20%, and PsA = 8%). A total of 31 (1.1%) patients developed tuberculosis during treatment. One patient on abatacept and one on tocilizumab developed TB while all the others were on TNF-inhibitors(29). The median (interquartile range) exposure to the current DAMRD course was 11.1 (5.9-20) months. TB patients did not significantly differ from others regarding disease duration, sex or age. Almost half (n=14,45%) of TB patients did not present evidence of previous exposure or any screening positive test for TB; 9 (29%) TB patients had received adequate LTBI treatment (isoniazid) recently or in the past. Furthermore, 8(26%) had incomplete/inconsistent screening. The overall incidence of TB was 1.9/1000 patients/year, and was not significantly different among the diseases (1.63 for RA, 2.06, for AS, and 3.79/1000/year for PsA). In univariate analysis, exposure to anti-TNF monoclonal antibodies (HR 3.1, 95%CI 1.18-8.15, P=0.02) and presence of any marker of previous contact with TB (positive history of TB, known contact with TB, positive TST, or abnormal chest X-ray: HR 4.2 (2.1-8.5, p Conclusion: Monoclonal anti-TNF antibodies and previous exposure/diagnosis of TB are independent risk factors for developing TB in Brazil. TB cases occurred both early and lately during treatment courses, suggesting LTBI screening failures, treatment non-adherence or re-exposure. Current application and content of the protocol for screening and treatment of LTBI needs to be reviewed. References [1] WHO TB report2018.https://www.who.int/tb/publications/global_report/en/ [2] Rev Bras Reumatol Engl Ed. 2017;57Suppl 2:477-483. doi: 10.1016/j.rbre.2017.05.005. Acknowledgement: monitor P Cabral, MDs N Sacilotto, H Pereira, F Sztajnbok. Disclosure of Interests: Ana Medeiros: None declared, M Bredemeier: None declared, V Valim: None declared, M Pinheiro Consultant for: Janssen, Pfizer, Speakers bureau: Abbot,Janssen,Novartis, C Macieira: None declared, A Duarte: None declared, B Stadler: None declared, R Ranza: None declared, M Bertolo: None declared, J Miranda Speakers bureau: Pfizer, C Brenol Speakers bureau: Pfizer, Roche, Janssen, Bristol., G Castro: None declared, V Fernandes Speakers bureau: Janssen, D Titton: None declared, F Sauma: None declared, I Pereira: None declared, R Botelho: None declared, H Carvalho: None declared, A Hayata: None declared, P Louzada: None declared, A Ranzolin: None declared, S Studart: None declared, G Castelar: None declared, A Kakehasi Grant/research support from: Abbvie, UCB, JANSSEN, ROCHE, NOVARTIS, PFIZER, Consultant for: Abbvie, UCB, JANSSEN, ROCHE, NOVARTIS, PFIZER, Paid instructor for: JANSSEN, Speakers bureau: Abbvie, UCB, JANSSEN, ROCHE, NOVARTIS, PFIZER, W Bianchi: None declared, R Acayaba: None declared, I Silveira: None declared, H Resende: None declared, J Amaral: None declared, L Rocha: None declared, M Gazzeta: None declared, L Carvalho: None declared, S Schowalski: None declared, D Feldman: None declared, I Laurindo Consultant for: Abbvie, UCB, GSK, JANSSEN, LILLY, NOVARTIS, PFIZER, Paid instructor for: Abbvie, JANSSEN, Speakers bureau: Abbvie, UCB, GSK, JANSSEN, LILLY, NOVARTIS, PFIZER, ROCHE, J Provenza: None declared

Background The combination of methotrexate (MTX) with leflunomide (LEF), despite being effective in the therapy of rheumatoid arthritis (RA)[1], has not been widely accepted[2,3]. In spite of evidence that the MTX-LEF combination is generally safe [1,4,5], the relatively small number of patients and treatment courses have not permitted firm conclusions. Objectives To evaluate the safety of the combination MTX-LEF in Brazilian patients with RA included in BiobadaBrasil. Methods BiobadaBrasil is a multicentric prospective cohort study involving patients with rheumatic diseases who started the first biologic or a synthetic disease modifying anti-rheumatic drug (DMARD)[6]. This analysis includes RA (2010 criteria) patients recruited from Jan 2009 to Aug 2018,followed-up for one or multiple courses of treatment until censoring (latest date, September 03, 2018) or occurrence of the outcome of interest. The primary outcome was the incidence of any serious AE (SAE). Secondary outcomes were infectious, non-mycobacterial pulmonary infectious, hepatic, hematologic and cardiovascular SAE. Multivariate Cox proportional hazards models (with DMARDs included as time-varying covariates) were used to estimate hazard ratios (HR) and 95% confidence intervals (CI); analyses were performed with the Survival package of R. Results Sample: 2055 RA patients, female=85.1%, median disease duration=6.02 yrs; mean (SD) age=50.3 (12.1) yrs; mean (SD) DAS28=5.3 (3.1); seronegative RA=14.1%; median follow-up duration=3.9 yrs. In total, 565 patients received 664 courses of the MTX-LEF combination (median duration, 2.5 years/course; 2209 person-years). The incidence of SAE was 4.75/100 patient-years in the entire sample. There was no significant increase in the risk of any of the outcomes with the use of combined therapy (table 1) comparing with methotrexate (without leflunomide). The use of antimalarials was associated with reduced risk of SAE (adjusted HR=0.62, 95% CI 0.48 to 0.79, P Conclusion BIOBADABRASIL results suggest that the combination of methotrexate and leflunomide is safe in thetreatment of RA. References [1] Ann Intern Med 2002; 137: 726. [2] Ann Rheum Dis 2010; 69: 43. [3] Ann Pharma cother 2004; 38: 1206. [4] J Rheumatol 2013; 40: 228. [5] Rev Bras Reumatol 2011; 51: 141/51:152. Acknowledgement monitor P Cabral Disclosure of Interests Markus Bredemeier: None declared, M Pinheiro Consultant for: Janssen, Pfizer, Speakers bureau: Abbot,Janssen,Novartis, C Macieira: None declared, A Duarte: None declared, B Stadler: None declared, R Ranza: None declared, Ana Medeiros: None declared, V Valim: None declared, M Bertolo: None declared, J Miranda Speakers bureau: Pfizer, C Brenol Speakers bureau: Pfizer, Roche, Janssen, Bristol., G Castro: None declared, V Fernandes Speakers bureau: Janssen, D Titton: None declared, F Sauma: None declared, I Pereira: None declared, R Botelho: None declared, H Carvalho: None declared, A Hayata: None declared, P Louzada: None declared, A Ranzolin: None declared, I Silveira: None declared, S Schowalski: None declared, D Feldman: None declared, I Laurindo Consultant for: Abbvie, UCB, GSK, JANSSEN, LILLY, NOVARTIS, PFIZER, Paid instructor for: Abbvie, JANSSEN, Speakers bureau: Abbvie, UCB, GSK, JANSSEN, LILLY, NOVARTIS, PFIZER, ROCHE, J Provenza: None declared

Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries.We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs.Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016.While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Background:After failure of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in the therapy of rheumatoid arthritis (RA), treatment may be escalated to biologic (bDMARDs) or JAK inhibitors (JAKi) (1). Analysis of drug survival can provide useful information on the effectiveness of these therapeutic schemes.Objectives:to evaluate the association of the choice of therapeutic agent with the survival of treatment course in RA patients receiving their first bDMARD or JAKi.Methods:BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients starting their first bDMARD/JAKi (2). This analysis includes RA patients recruited from Jan 2009 to Oct 2019, followed-up over the first course of treatment with a bDMARD/JAKi until censoring (latest date, Nov 19, 2019) or occurrence of the outcome of interest. A treatment course is defined as a period during which the medication scheme does not change, except for dose adjustments. The primary outcome was the interruption of treatment course for any reason (except for pregnancy or disease remission); interruption of treatment due to adverse events (AEs) or death and due to inefficacy served as secondary outcomes. Multivariate Cox proportional hazards models were used for analyses.Results:In total, 1177 patients (3800 patient-years [PY]) were enrolled. The overall incidence of treatment interruption was 17.5/100 PY. Adalimumab was the most frequently prescribed agent, followed by infliximab (n= 267). The hazards ratios (HR) of the primary and secondary outcomes are presented in Table 1. Figure 1 compares the survival of treatment curves of different bDMARDs/JAKi.Table 1.Hazard ratios (HR) of interruption of therapy course of each therapeutic agent (the reference category for bDMARDs/ JAKi is infliximab). Results are HR, 95% CIs, and P values*.Agent (number of patients)Interruption for any reason (665 events)Interruption due to adverse events or death (196 events)Interruption due to inefficacy (319 events)Adalimumab (354)0.83 (0.68 to 1.01), P= 0.0620.68 (0.48 to 0.96), P=0.0291.08 (0.80 to 1.44), P=0.621Etanercept (257)0.81 (0.66 to 1.01), P=0.0630.56 (0.37 to 0.83), P=0.0040.93 (0.68 to 1.29), P=0.674Certolizumab (80)0.74 (0.47 to 1.16), P=0.1850.33 (0.13 to 0.86), P=0.0241.32 (0.74 to 2.35), P=0.350Golimumab (53)0.86 (0.53 to 1.38), P=0.5300.46 (0.18 to 1.19), P=0.1111.07 (0.53 to 2.15), P=0.849JAKi (tofacitinib) (59)0.54 (0.30 to 0.99), P=0.0470.19 (0.04 to 0.82), P=0.0260.89 (0.41 to 1.96), P=0.779Rituximab (48)0.87 (0.55 to 1.37), P=0.5400.48 (0.20 to 1.18), P=0.1090.58 (0.26 to 1.34), P=0.205Abatacept (30)0.52 (0.25 to 1.07), P=0.0770.46 (0.14 to 1.56), P=0.2150.46 (0.14 to 1.52), P=0.203Tocilizumab (29)0.29 (0.14 to 0.63), P=0.0020.40 (0.12 to 1.30), P=0.1260.28 (0.09 to 0.90), P=0.033Methotrexate (792)0.95 (0.79 to 1.14), P=0.5610.86 (0.62 to 1.19), P=0.3620.98 (0.75 to 1.28), P=0.860Leflunomide (497)1.17 (0.99 to 1.39), P=0.0611.44 (1.06 to 1.96), P=0.0201.02 (0.80 to 1.30), P=0.856Sulfasalazine (48)1.18 (0.80 to 1.75), P=0.4011.94 (1.07 to 3.54), P=0.0300.85 (0.45 to 1.59), P=0.605Antimalarials (230)0.80 (0.65 to 0.98), P=0.0270.67 (0.45 to 0.99), P=0.0430.67 (0.50 to 0.92), P=0.011* All tests adjusted for other variables presented in the table and for age, baseline DAS28, disease duration, gender, smoking, seropositivity (RF/anti-CCP), previous malignancy, diabetes, hypertension, hypercholesterolemia, renal failure, ischemic cardiomyopathy, COPD, heart failure, use of corticosteroids, starting year, hypercholesterolemia, osteoporosis, hepatitis B and C.Conclusion:In our study, infliximab was related to an overall higher hazard of treatment course interruption than tolicizumab and tofacitinib, and higher hazard of interruption due to AEs than most other anti-TNF agents and tofacitinib. Maintaining antimalarials in patients receiving advanced therapies for RA may reduce interruption of treatment due to inefficacy and AEs.Disclosure of Interests:None declared

Previous studies have shown that high levels of air pollutants may increase activity of systemic lupus erythematosus (SLE). The aim of this study is to analyze the association between pollutants originating from the Brazilian Legal Amazon and SLE activity. This is a retrospective longitudinal cohort study with patients with SLE in the General Hospital in Cuiab&aacute, Brazil. The association with SLE activity was measured using the SLE disease activity index (SLEDAI) and data on air quality&mdash, PM2.5 and CO, published on the websites of the State Department of Environment and the Center for Weather Forecasting and Climate Studies. To assess the effect of daily concentrations of pollutants on SLEDAI scores, the generalized estimation equation (GEE) model was used. A total of 32 female patients were assessed, in 96 doctor&rsquo, s appointments. The average SLEDAI score was 6 points (&plusmn, 5.05). GEE showed an association of disease activity with both higher rates of wildfires (p = 0.021) and average CO rate (p = 0.013), but there was no statistical association between particulate levels and SLE activity. The results suggest that variations in air pollution are associated with the activity of autoimmune rheumatic diseases.

Objectives To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. Patients and methods This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Statistical analysis: Unpaired t-test and Fisher's two-tailed test; p < 0.05. Results The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab = 676, infliximab = 547 and etanercept = 521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab = 4.43/1000 patient-years; etanercept = 1.92/1000 patient-years and infliximab = 1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. Conclusions The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure. Resumo Objetivos Avaliar incidência de tuberculose e triagem para tuberculose latente em brasileiros com artrite reumatoide em uso de agentes biológicos na prática clinica. Pacientes e métodos Estudo de coorte com dados do Registro Brasileiro de Monitoração de Terapias Biológicas (BiobadaBrasil), de 01/2009 a 05/2013, abrangeu 1.552 tratamentos, 415 somente com drogas modificadoras do curso da doença (MMCDs) sintéticas, 942 MMCDs sintéticas em associação com anti-TNF (etanercepte, infliximabe, adalimumabe) e 195 MMCDs sintéticas em associação com outros biológicos (abatacepte, rituximabe e tocilizumabe). Avaliaram-se ocorrência de tuberculose, tempo de exposição às drogas e triagem para TB. Análise estatística: teste t não pareado e teste de Fisher bicaudal; p < 0,05. Resultados O tempo de exposição dos controles foi de 981 pacientes-ano, do grupo de anti-TNF foi de 1.744 pacientes-ano (adalimumabe = 676, infliximabe = 547 e etanercepte = 521 pacientes-ano) e o de outros biológicos de 336 pacientes-ano. A incidência de TB foi de 1,01/1.000 pacientes-ano nos controles e de 2,87 pacientes-ano nos usuários de anti-TNF (adalimumabe = 4,43/1.000 pacientes-ano; etanercepte = 1,92/1.000 pacientes-ano e infliximabe = 1,82/1.000 pacientes-ano). Não houve casos de tuberculose no grupo de outros biológicos. O tempo médio de exposição até a ocorrência de tuberculose foi de 27(11) meses para o grupo anti-TNF. Conclusões A incidência de tuberculose foi maior nos usuários de MMCDs sintéticas e anti-TNF do que nos usuários de MMCDs sintéticas e de MMCDs sintéticas e biológicos não anti-TNF, e também mais tardia, sugerindo infecção durante o tratamento, e não falha na triagem.

INTRODUÇÃO: A artrite reumatoide (AR) é uma doença inflamatória crônica, com caráter sistêmico e progressivo, caracterizada pelo envolvimento articular que pode resultar em deformidade e incapacidade funcional. No mundo, a realidade de diagnóstico, tratamento e seguimento de pacientes com AR é muito variável. As principais sociedades de reumatologia, assim como os órgãos governamentais da maioria dos países, tentam estabelecer recomendações direcionando os critérios de diagnóstico, tratamento e seguimento para AR. O avanço rápido na descoberta de novas drogas, com respostas terapêuticas cada vez mais eficientes, não tem sido acompanhado da atualização dessas recomendações, e esforços devem ser feitos para uniformizar os procedimentos estabelecidos. OBJETIVO: comparar as principais recomendações de tratamento da AR com os protocolos brasileiros, da SBR e do Ministério da Saúde. MÉTODOS: Foram analisados os protocolos para tratamento da AR do Ministério da Saúde do Brasil, da Sociedade Brasileira de Reumatologia, da PANLAR/GLADAR, do Colégio Americano de Reumatologia (ACR), da Liga Europeia contra o Reumatismo (EULAR) e do Colégio Mexicano de Reumatologia. RESULTADOS: Diferenças importantes foram identificadas entre as diversas recomendações com destaque para os critérios de início das terapias biológicas, sequência hierárquica para uso dos biológicos disponíveis, assim como para a suspensão ou troca entre estes. CONCLUSÕES: É necessária a atualização mais rápida das recomendações de tratamento da AR. A padronização universal de critérios para elaboração de recomendações seria de grande valia para nortear regiões e países do mundo em torno de conduta semelhante por parte dos reumatologistas.

OBJETIVOS: O presente estudo teve por objetivo descrever o processo de implementação de um registro nacional em um país em desenvolvimento (Brasil) e relatar os principais resultados preliminares do registro BiobadaBrasil. MATERAL E MÉTODOS: Através de um acordo com a PANLAR, o protocolo Biobadaser foi utilizado como modelo para a implementação de um novo registro no nosso país. Durante os dois primeiros anos desse esforço, o protocolo original foi adaptado, traduzido e apresentado a todos os reumatologistas brasileiros. Durante dez meses, dados de 1.037 pacientes (750 tratados com biológicos e 287 controles) de 15 centros foram coletados. RESULTADOS: A maioria dos pacientes tinha artrite reumatoide (AR) (n = 723). Infliximabe foi o agente anti-TNF mais usado, e a exposição total a biológicos foi 2.101 pacientes-ano. A razão mais comum para suspensão da droga foi ineficiência ou perda de efetividade (50%), e 30% dos pacientes interromperam o tratamento devido a eventos adversos. Três casos de tuberculose foram observados no grupo biológico, representando maior incidência do que aquela da população brasileira geral. Infecções foram observadas em 23% dos pacientes do grupo biológico, sendo o trato respiratório superior o local mais comumente afetado. Apenas um caso de hanseníase tuberculoide foi observado. Nenhuma morte nem malignidade atribuível ao efeito dos medicamentos foi observada até fevereiro de 2010. CONCLUSÕES: A implementação do registro foi bem sucedida. Embora recente, o registro BiobadaBrasil já forneceu importantes dados. OBJECTIVES: The present study aimed at describing the implementation process of a national registry in a developing country (Brazil) and at reporting the main preliminary results of the BiobadaBrasil registry. MATERIAL AND METHODS: Through a PANLAR agreement, the Biobadaser protocol was used as a model for implementing the new registry in our country. During the first two years of this effort, the original protocol was adapted, translated, and presented to all Brazilian rheumatologists. For ten months, data of 1,037 patients (750 subjects treated with biological drugs and 287 control subjects) from 15 centers were collected. RESULTS: Most patients had rheumatoid arthritis (RA) (n = 723). Infliximab was the most frequently used anti-TNF agent, and the total exposure to biologic drugs was 2,101 patient-years. The most common reason for interrupting drug use was lack or loss of efficacy (50%), while 30% withdrew from the treatment arm due to adverse events. Three cases of tuberculosis were observed in the biologic group, with an incidence higher than that of the general Brazilian population. Infections were observed in 23% of the biologic group, and the upper respiratory tract was the most commonly affected site. Only one case of tuberculoid leprosy was observed. No deaths or malignancies attributed to drug effects were observed as of February 2010. CONCLUSIONS: The implementation of the BiobadaBrasil registry was successful, and, although recent, the registry has provided important data.

Background.Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem, and autoimmune disease.Objective.The aim of this study was to describe the prevalence of hyposalivation in SLE patients and evaluate factors associated.Methods.This is a cross-sectional study developed at the Cuiaba University General Hospital (UNIC-HGU), Mato Grosso, Brazil. The study population consisted of female SLE patients treated at this hospital from 06/2010 to 12/2012. Unstimulated salivary flow rates (SFRs) were measured. Descriptive and inferential analyses were performed in all cases using a significance levelP<0.05.Results.The results showed that 79% of patients with systemic lupus erythematosus suffered from hyposalivation and that the disease activity and age in years were the factors that resulted in statistically significant differences.Conclusion.The activity of the disease, age >27 years, and the drugs used were factors associated with hyposalivation, resulting in a statistically significant decrease in saliva production.

Objective To describe the development of 4 new cases of leishmaniasis in patients receiving anti-tumor necrosis factor-α (anti-TNF) agents and review the pertinent literature. Methods Chart review of the 4 cases and MEDLINE search for additional reported cases. Results All reported cases, including ours, came from endemic areas. The infection was detected on an average of 23.5 months after the initiation of anti-TNF therapy. The majority of cases had the classical clinical presentation. The biological therapy was suspended in 21 cases. The results were successful for leishmaniasis therapy in all cases. In 10 cases it was possible to reintroduce anti-TNF agents. On follow-up it was observed that there was an infection relapse in 3 cases. Conclusions The present study shows that leishmaniasis, in its several clinical forms, should be included in the differential diagnosis of possible infections involving patients under use of aTNF therapy. Endemic disease under geographic expansion, easy international displacement and intense human migratory flows certainly represents a risk of this infection in an increasing universe of people which includes the immunosuppressed patients. Cutaneous lesions, prolonged fever, splenomegaly, and pancytopenias, the main clinical-laboratory findings of leishmaniasis, can also be present in autoimmune rheumatic disease, thus leading to delayed diagnosis and treatment of the parasitic disease. The diagnosis depends basically on a high suspicion index, being confirmed with the identification of the protozoan. The classic treatment of the infection when instituted is associated with complete recovery. It is important to point out that all cases reported so far had either originated from or been recently in regions regarded as endemic of leishmaniasis.

The present study aimed at describing the implementation process of a national registry in a developing country (Brazil) and at reporting the main preliminary results of the BiobadaBrasil registry.Through a PANLAR agreement, the Biobadaser protocol was used as a model for implementing the new registry in our country. During the first two years of this effort, the original protocol was adapted, translated, and presented to all Brazilian rheumatologists. For ten months, data of 1,037 patients (750 subjects treated with biological drugs and 287 control subjects) from 15 centers were collected.Most patients had rheumatoid arthritis (RA) (n = 723). Infliximab was the most frequently used anti-TNF agent, and the total exposure to biologic drugs was 2,101 patient-years. The most common reason for interrupting drug use was lack or loss of efficacy (50%), while 30% withdrew from the treatment arm due to adverse events. Three cases of tuberculosis were observed in the biologic group, with an incidence higher than that of the general Brazilian population. Infections were observed in 23% of the biologic group, and the upper respiratory tract was the most commonly affected site. Only one case of tuberculoid leprosy was observed. No deaths or malignancies attributed to drug effects were observed as of February 2010.The implementation of the BiobadaBrasil registry was successful, and, although recent, the registry has provided important data.

Rheumatoid arthritis (RA) is a chronic systemic and progressive inflammatory disorder of the joints, which can result in deformity and functional disability. The diagnosis, treatment, and follow-up of patients with RA vary worldwide. The major societies of rheumatology, as well as governmental agencies in most countries, have tried to establish recommendations addressing diagnosis, treatment, and follow-up of RA. Despite the rapid advance in discovering new drugs, with increasingly efficient therapeutic responses, these recommendations have not been updated accordingly. Thus, efforts should be focused on standardizing the procedures established.Compare the main international recommendations for treatment of RA with the Brazilian protocols of the Brazilian Society of Rheumatology and Ministry of Health.The protocols of the following entities for treating RA were assessed: Brazilian Ministry of Health, Brazilian Society of Rheumatology, PANLAR/GLADAR, American College of Rheumatology, European League Against Rheumatism (EULAR), and Mexican College of Rheumatology.Significant differences were identified between the several recommendations, especially regarding the criteria for beginning biological therapies, hierarchic sequence for using available biological drugs, and for suspending or switching them.The recommendations for treatment of RA should be more frequently updated. The worldwide standardization of criteria for elaborating recommendations would be of great value to provide similar guidance to rheumatologists in countries and regions throughout the world.

To evaluate and compare clinical and laboratory features of gout in men and women.Twenty-seven women and 31 men with gout underwent clinical and laboratory evaluation and review of medical records.Disease onset in women was a mean of 7 years later than in men. There were no differences between women and men regarding systemic hypertension, diabetes mellitus, hyperlipidemia, chronic renal failure, renal stones, ischemic heart disease, or heavy alcohol consumption. Tophaceous gout was similar in both groups, although female gender seemed to be protective against risk of developing tophi (odds ratio: 0.449; 95% confidence interval: 0.151-1.330). Podagra was more common in men, and women showed a higher frequency of upper limb joint involvement. Most patients had low urate excretion rates. Achieving disease control was similar in women and men. Of the 8 women who were premenopausal at disease onset, 7 had secondary causes for gout; 5 of the 8 had high serum urate despite treatment.Gout in women had a later onset and higher frequency of upper limb joint involvement in comparison to men. Those with premenopausal onset tended to be refractory to standard therapy.