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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

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

Tumor necrosis factor-α (TNF-α) inhibitors are increasingly becoming the standard of care for treating a number of inflammatory diseases. However, treatment with TNF-α inhibitors carries an inherent risk of compromising the immune system, resulting in an increased susceptibility to infections and malignancies. This increased risk of infection is of particular concern in Asia, Eastern Europe, and Latin America where tuberculosis (TB) and viral hepatitis are endemic. In this brief review, we examine the literature and review the impact of TNF-α inhibitors on the incidence and the reactivation of latent disease with respect to TB, hepatitis C infection, and hepatitis B infection. Our findings show that TNF-α inhibitors are generally safe, if used with caution. Patients should be screened prior to the initiation of TNF-α inhibitor treatment and given prophylactic treatment if needed. In addition, patients should be monitored during treatment with TNF-α inhibitors and after treatment has stopped to ensure that infections, if detected, are treated promptly and effectively. Our analysis is consistent with other reports and guidelines.

ResumoObjetivoAvaliar os resultados da aplicação do Índice de Atividade de Doença da Espondilite Anquilosante de Bath (BASDAI) numa série de pacientes brasileiros com EpA e estabelecer suas correlações com as variáveis específicas do grupo.MétodosUm protocolo comum de investigação foi prospectivamente aplicado em 1.492 pacientes brasileiros classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartropatias (ESSG), acompanhados em 29 centros de referência em reumatologia no Brasil. Variáveis clínicas, demográficas e índices de doença foram colhidos. Os valores totais do BASDAI foram comparados com a presença das diferentes variáveis.ResultadosO valor médio do BASDAI foi de 4,20 ± 2,38. Os escores médios do BASDAI foram mais elevados nos pacientes com forma clínica combinada, comparado às formas axiais e periféricas isoladas, nos pacientes do sexo feminino e nos sedentários. Com relação ao componente axial, valores mais altos do BASDAI estiveram significativamente associados à lombalgia inflamatória, à dor alternante em nádegas, à dor cervical e ao acometimento de coxofemorais. Houve associação estatística entre os valores do BASDAI e o comprometimento periférico, relacionado ao número de articulações inflamadas, tanto dos membros inferiores quanto dos membros superiores, e às entesites. A positividade do HLA‐B27 e a presença de manifestações extra‐articulares não estiveram correlacionadas com os valores médios do BASDAI. Valores mais baixos do BASDAI estiveram associados ao uso de agentes biológicos (p

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.

The aim of the present study was to analyze the score of fatigue in a large cohort of Brazilian patients with SpA, comparing different disease patterns and its association with demographic and disease-specific variables.A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyloarthropathies Study Group (ESSG) criteria, attended at 29 reference centers. Clinical and demographic variables were recorded. Fatigue was evaluated using the first item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire.The mean BASDAI fatigue score was 4.20 ± 2.99. There was no significant difference in the fatigue score between the different SpA. Fatigue was higher in female patients (p0.001), with mixed (axial + peripheral) involvement (p0.001) and in those who did not practice exercises (p0.001). Higher scores of fatigue were significantly associated with inflammatory low back pain (p = 0.013), alternating buttock pain (p = 0.001), cervical pain (p = 0.001), and hip involvement (p = 0.005). Fatigue presented a moderate positive statistical correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) (0.469; p0.001) and Ankylosing Spondylitis Quality of Life (0.462; p0.001).In this large series of Brazilian SpA patients, higher fatigue scores were associated with female gender, sedentary, worse functionality, and quality of life.

Introdução: Poucos estudos avaliaram o perfil do uso de drogas modificadoras de doença (DMD) em pacientes brasileiros com diagnóstico de espondiloartrite (EpA). Métodos: Um protocolo comum de investigação foi prospectivamente aplicado em 1505 pacientes classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartrites (ESSG), acompanhados em 29 centros de referência em Reumatologia no Brasil. Variáveis clínicas e demográficas foram obtidas e avaliadas, analisando-se suas correlações com o uso das DMD metotrexato (MTX) e sulfasalazina (SSZ). Resultados: Pelo menos uma DMD foi utilizada por 73,6% dos pacientes, sendo MTX por 29,2% e SSZ por 21,7%, enquanto 22,7% utilizaram ambas as drogas. O uso do MTX foi significativamente associado ao acometimento periférico, e a SSZ foi associada ao comprometimento axial, sendo que as duas drogas foram mais utilizadas, isoladas ou combinadas, no comprometimento misto (p < 0,001). O uso de uma DMD esteve significativamente associado à etnia branca (MTX; p = 0,014), lombalgia inflamatória (SSZ; p = 0,002), dor em nádegas (SSZ; p = 0,030), cervicalgia (MTX; p = 0,042), artrite de membros inferiores (MTX; p < 0,001), artrite de membros superiores (MTX; p < 0,001), entesite (p = 0,007), dactilite (MTX; p < 0,001), doença inflamatória intestinal (SSZ; p < 0,001) e acometimento ungueal (MTX; p < 0,001). Conclusão: O uso de pelo menos uma DMD foi referido por mais de 70% dos pacientes numa grande coorte brasileira de pacientes com EpA, sendo o uso do MTX mais associado ao acometimento periférico e o uso da SSZ mais associado ao acometimento axial. Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). Results: At least one DMD was used by 73.6 % of patients: MTX by 29.2 % and SSZ by 21.7%, while 22.7 % used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Objective: To analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (+/- 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African Brazilian ethnicity (p

Objective.Spondyloarthritides (SpA) can present different disease spectra according to ethnic background. The Brazilian Registry of Spondyloarthritis (RBE) is a nationwide registry that comprises a large databank on clinical, functional, and treatment data on Brazilian patients with SpA. The aim of our study was to analyze the influence of ethnic background in SpA disease patterns in a large series of Brazilian patients.Methods.A common protocol of investigation was prospectively applied to 1318 SpA patients in 29 centers distributed through the main geographical regions in Brazil. The group comprised whites (65%), African Brazilians (31.3%), and people of mixed origins (3.7%). Clinical and demographic variables and various disease index scores were compiled. Ankylosing spondylitis (AS) was the most frequent disease in the group (65.1%); others were psoriatic arthritis (18.3%), undifferentiated SpA (6.8%), enteropathic arthritis (3.7%), and reactive arthritis (3.4%).Results.White patients were significantly associated with psoriasis (p = 0.002), positive HLA-B27 (p = 0.014), and use of corticosteroids (p < 0.0001). Hip involvement (p = 0.02), axial inflammatory pain (p = 0.04), and radiographic sacroiliitis (p = 0.025) were associated with African Brazilian descent. Sex distribution, family history, and presence of peripheral arthritis, uveitis, dactylitis, urethritis, and inflammatory bowel disease were similar in the 3 groups, as well as age at disease onset, time from first symptom until diagnosis, and use of anti-tumor necrosis factor-α agents (p > 0.05). Schober test and thoracic expansion were similar in the 3 groups, whereas African Brazilians had higher Maastricht Ankylosing Spondylitis Enthesitis Scores (p = 0.005) and decreased lateral lumbar flexion (p = 0.003), while whites had a higher occiput-to-wall distance (p = 0.02). African Brazilians reported a worse patient global assessment of disease (p = 0.011). Other index scores and prevalence of work incapacity were similar in the 3 groups, although African Brazilians had worse performance in the Ankylosing Spondylitis Quality of Life questionnaire (p < 0.001).Conclusion.Ethnic background is associated with distinct clinical aspects of SpA in Brazilian patients. African Brazilian patients with SpA have a poorer quality of life and report worse disease compared to whites.

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.

Gustavo G. Resende a,*, Cristina C. D. Lannaa, Adriana B. Bortoluzzob, Celio R. Goncalvesc, Percival D. Sampaio -Barrosc, Jose Antonio Braga da Silvad, Antonio Carlos Ximenese, Manoel B. Bertolo f, Sandra L.E. Ribeiro g, Mauro Keisermanh, Rita Menini, Thelma L. Skare j, Sueli Carneirok, Valderilio F. Azevedol, Walber P. Vieiram, Elisa N. Albuquerquen, Washington A. Bianchio, Rubens Bonfiglioli p, Cristiano Campanholoq, Hellen M. S. Carvalhor, Izaias P. Costas, Angela P. Duartet, Charles L. Kohemu, Nocy Leitev, Sonia A. L. Limaw, Eduardo S. Meirelles x, Ivânio A. Pereiray, Marcelo M. Pinheiro z, Elizandra Polito A, Francisco Airton C. RochaB, Mittermayer B. SantiagoC, Maria de Fatima L. C. SaumaD, Valeria ValimE

Objetivo Analisar as características clínicas e epidemiológicas das espondiloartrites (EpA) de início juvenil (< 16 anos) e compará-las com um grupo de pacientes com EspA de início na vida adulta (≥ 16 anos). Pacientes e métodos Coorte prospectiva, observacional e multicêntrica com 1.424 pacientes com diagnóstico de EspA de acordo com o European Spondyloarthropathy Study Group (ESSG) submetidos a um protocolo comum de investigação e recrutados em 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE). Os pacientes foram divididos em dois grupos: idade no início

As doenças inflamatórias intestinais (doença de Crohn e retocolite ulcerativa) apresentam manifestações extraintestinais em um quarto dos pacientes, sendo a mais comum a artrite enteropática. MÉTODOS: Estudo prospectivo, observacional e multicêntrico, realizado com pacientes de 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE), que se incorpora ao grupo RESPONDIA (Registro Ibero-americano de Espondiloartrites). Dados demográficos e clínicos de 1472 pacientes foram colhidos, e aplicaram-se questionários padronizados de avaliação de mobilidade axial, de qualidade de vida, de envolvimento entesítico, de atividade de doença e de capacidade funcional. Exames laboratoriais e radiográficos foram realizados. Objetivamos, neste presente artigo, comparar as características clínicas, epidemiológicas, genéticas, imagenológicas, de tratamento e prognóstico de enteroartríticos com os outros espondiloartríticos nesta grande coorte brasileira. RESULTADOS: Foram classificados como enteroartrite 3,2% dos pacientes, sendo que 2,5% tinham espondilite e 0,7%, artrite (predomínio periférico). O subgrupo de indivíduos com enteroartrite apresentava maior prevalência de mulheres (P < 0,001), menor incidência de dor axial inflamatória (P < 0,001) e de entesite (P = 0,004). O HLA-B27 foi menos frequente no grupo de enteroartríticos (P = 0,001), mesmo se considerado apenas aqueles com a forma axial pura. Houve menor prevalência de sacroiliíte radiológica (P = 0,009) e também menor escore radiográfico (BASRI) (P = 0,006) quando comparado aos pacientes com as demais espondiloartrites. Também fizeram mais uso de corticosteroides (P < 0,001) e sulfassalasina (P < 0,001) e menor uso de anti-inflamatórios não hormonais (P < 0,001) e metotrexato (P = 0,001). CONCLUSÃO: Foram encontradas diferenças entre as enteroartrites e as demais espondiloartrites, principalmente maior prevalência do sexo feminino, menor frequência do HLA-B27, associados a uma menor gravidade do acometimento axial. Inflammatory bowel diseases (Crohn’s disease and ulcerative rectocolitis) have extraintestinal manifestations 25% of the patients, with the most common one being the enteropathic arthritis. Methods: Prospective, observational, multicenter study with patients from 29 reference centers participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the assessment of axial mobility, quality of life, enthesitic involvement, disease activity and functional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treatment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort. Results: A total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spondylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with enteroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less nonsteroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001). Conclusion: There were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.

IntroductionFew studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA).MethodsA common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ).ResultsAt least one DMD was used by 73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX, p = 0.014), inflammatory back pain (SSZ, p = 0.002), buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001).ConclusionThe use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

OBJETIVO: Descrever as manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas) geralmente não relacionadas às espondiloartrites (EpA) em uma grande coorte de pacientes brasileiros. MÉTODOS: Este estudo retrospectivo analisou 1.472 pacientes com o diagnóstico de EpA atendidos em 29 centros distribuídos pelas cinco principais regiões geográficas do Brasil, integrantes do Registro Brasileiro de Espondiloartrites. Todos os pacientes foram avaliados para a prevalência das principais manifestações extra-articulares (cardíacas, renais, pulmonares e neurológicas), divididas por diagnóstico [espondilite anquilosante (EA), artrite psoriásica (AP), artrite reativa (ARe), artrite associada a doença inflamatória intestinal (DII), EpA indiferenciada (EI) e EpA juvenil] e por forma clínica (axial, periférica, mista e entesítica). RESULTADOS: Dentre os pacientes avaliados com EpA, 963 apresentavam EA, 271 AP, 49 ARe, 48 artrite associada a DII, 98 EI e 43 EpA juvenil. Acometimento cardíaco foi observado em 44 pacientes (3,0%), seguido por acometimento pulmonar em 19 (1,3%), renal em 17 (1,2%) e neurológico em 13 pacientes (0,9%). A maioria dos casos de acometimento visceral ocorreu nos pacientes com EA ou AP e naqueles com forma clínica mista (axial e periférica) e/ou predominantemente axial. CONCLUSÃO: As manifestações extra-articulares cardíacas, renais, pulmonares e neurológicas são muito pouco frequentes nas EpA, variando de 0,9%-3% nesta grande coorte brasileira, estando mais associadas a EA e AP. OBJECTIVE: To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients. MATERIALS AND METHODS: This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis). RESULTS: Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form. CONCLUSION: Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA. Universidade de Fortaleza Hospital Geral de Fortaleza Hospital Geral de Fortaleza Serviço de Reumatologia Instituto de Ensino e Pesquisa FMUSP Hospital das Clínicas Universidade de Brasília Hospital Geral de Goiânia Universidade Estadual de Campinas Universidade Federal do Amazonas Pontifícia Universidade Católica de Porto Alegre Faculdade de Medicina de São José do Rio Preto Hospital Evangélico de Curitiba Universidade Federal do Rio de Janeiro Universidade Federal do Paraná Universidade do Estado do Rio de Janeiro Santa Casa da Misericórdia do Rio de Janeiro Pontifícia Universidade Católica de Campinas Santa Casa de Misericórdia de São Paulo Hospital de Base de Brasília Universidade Federal do Mato Grosso do Sul Universidade Federal de Pernambuco Universidade Federal do Rio Grande do Sul Fundação Técnico-Educacional Souza Marques Hospital do Servidor Público Estadual de São Paulo FMUSP Universidade Federal de Santa Catarina Universidade Federal de São Paulo (UNIFESP) Santa Casa de Misericórdia de Belo Horizonte Universidade Federal de Minas Gerais Universidade Federal do Ceará Escola de Saúde Pública da Bahia Universidade Federal do Pará Universidade Federal do Espírito Santo UNIFESP, EPM, São Paulo SciELO

Objetivo: analisar as variáveis demográficas e clínicas associadas à diminuição da qualidade de vida em uma grande coorte brasileira de pacientes com espondiloartrite (EpA). Métodos: Foi aplicado um protocolo de pesquisa único a 1.465 pacientes brasileiros classificados como tendo EpA de acordo com os critérios do European Spondyloarthropaties Study Group (ESSG), atendidos em 29 centros de referência em reumatologia do Brasil. Foram registradas as variáveis clínicas e demográficas. A qualidade de vida foi analisada por meio do questionário Ankylosing Spondylitis Quality of Life (ASQoL). Resultados: A pontuação média do ASQoL foi de 7,74 (+ 5,39). Ao analisar doenças específicas no grupo de EpA, as pontuações do ASQoL não apresentaram diferença estatisticamente significativa. Os dados demográficos mostraram piores escores de ASQoL associados ao gênero feminino (p = 0,014) e etnia negra (p < 0,001). Quanto aos sintomas clínicos, a dor na região glútea (p = 0,032), a dor cervical (p < 0,001) e a dor no quadril (p = 0,001), estiveram estatisticamente associadas a piores escores no ASQoL. O uso contínuo de fármacos anti-inflamatórios não esteroides (p < 0,001) e agentes biológicos (p = 0,044) esteve associado a escores mais elevados de ASQoL, enquanto outros medicamentos não interferiram nos escores do ASQoL. Conclusão: Nesta grande série de pacientes com EpA, o sexo feminino e a etnia negra, bem como sintomas predominantemente axiais, estiveram associados a uma qualidade de vida reduzida. Objective: to analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (± 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African-Brazilian ethnicity (p < 0.001). Regarding clinical symptoms, buttock pain (p = 0.032), cervical pain (p < 0.001) and hip pain (p = 0.001), were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biologic agents (p = 0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores. Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life.