Abstract Background A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil. Methods This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources. Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE. Results Overall, 300 patients with SLE were included (92.3% female, mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001). Conclusion These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country. (COI whole (SLE Brazil 12month, 12month month 12 month, 12-month crosssectional, crosssectional cross sectional, sectional cross-sectional ACR 199 Criteria questionnaires (questionnaires records covering profile morbidities 12Item Item Survey SF12, SF12 SF , SF-12) healthrelated health related consultations, consultations (consultations tests medications hospitalization nonhealthrelated non transportation, transportation (transportation adaptation caregivers consumed Overall 30 92.3% 923 92 3 (92.3 female standard SD 118 11 8 11. 7.9 79 7 9 [7.9 years, years years) 10 33.3% 333 33 (33.3% SLErelated 4 15.3% 153 15 (15.3% schooling (SD 44 4. 12.6 126 6 (12.6 hours 222 (22 74.0%. 740 74.0% . 74 0 [74.0%]) SF-1 ( 0117 117 0.117 0.042, 0042 0.042 042 0.042) CollaboratingClinicsAmericanCollegeofRheumatology CollaboratingClinics AmericanCollegeofRheumatology 0115 115 0.115 0.046, 0046 0.046 046 0.046) medicationsday day comorbidities co 0272 272 0.272 0.001, 0001 0.001 001 0.001) SLEspecific specific drugsday 0113 113 0.113 0.051, 0051 0.051 051 0.051) 0570 570 0.570 0.001. 0232 232 0.232 US312353patientyear USpatientyear US 123 53 year interquartile IQR US161851 1 618 51 US$1,618.5 $678.66, 67866 678 66 [$678.66 $4,601.29. 460129 $4,601.29 601 29 $4,601.29]) medication (IQR US91062 910 62 US$910.6 $460, 460 ($460 $4,033.51. 403351 $4,033.51 033 $4,033.51) 3664 664 3.66 erythrocyte Creactive C reactive protein 0381 381 0.38 biological social factors decisionmaking decision making country 19 SF1 92.3 (92. 7. [7. 33.3 (33.3 15.3 (15.3 12. (12. 22 (2 74.0 [74.0%] SF- 011 0.11 004 0.04 04 027 27 0.27 000 0.00 00 005 0.05 05 057 57 0.57 023 23 0.23 patientyear 5 US16185 61 US$1,618. $678.66 6786 67 [$678.6 46012 $4,601.2 60 2 $4,601.29] US9106 91 US$910. $460 ($46 40335 $4,033.5 03 366 3.6 038 38 0.3 92. (92 [7 33. (33. 15. (15. (12 74. [74.0% 01 0.1 0.0 02 0.2 0.5 US1618 US$1,618 $678.6 [$678. 4601 $4,601. US910 US$910 $46 ($4 4033 $4,033. 36 3. 0. (9 [ (33 (15 (1 [74.0 US161 US$1,61 $678. [$678 $4,601 US91 US$91 $4 ($ 403 $4,033 (3 [74. US16 US$1,6 $678 [$67 $4,60 US9 US$9 $ 40 $4,03 [74 US1 US$1, $67 [$6 $4,6 US$ $4,0 US$1 $6 [$ $4,

Abstract Background The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. Methods This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians’ perceptions of disease control were assessed using a numeric rating scale (NRS; 0—inactive to 10—very active disease). Results The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7–10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. Conclusion This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.

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.

Abstract 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.

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.

INTRODUCTION: 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. Objective: Compare the main international recommendations for treatment of RA with the Brazilian protocols of the Brazilian Society of Rheumatology and Ministry of Health. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.