Inês Guimarães da Silveira

Update on the brazilian consensus for the diagnosis and treatment of rheumatoid arthritis

Manoel Barros Bértolo(1), Claiton Viegas Brenol(2), Cláudia Goldenstein Schainberg(3), Fernando Neubarth(4), Francisco Aires Correa de Lima(5), Ieda Maria Laurindo(6), Inês Guimarães Silveira(7), Ivanio Alves Pereira(8), Marco Antonio Rocha Loures(9), Mario Newton de Azevedo(10), Max Victor Carioca de Freitas(11), Milton da Silveira Pedreira Neto(12), Ricardo Machado Xavier(13), Rina Dalva N. Giorgi(14), Sergio Candido Kowalski(15), Sonia Maria Alvarenga Anti(16)

Registro brasileiro de biológicos: processo de implementação e resultados preliminares do BiobadaBrasil

OBJETIVOS: O presente estudo teve por objetivo descrever o processo de implementacao de um registro nacional em um pais em desenvolvimento (Brasil) e relatar os principais resultados preliminares do registro BiobadaBrasil. MATERAL E METODOS: Atraves de um acordo com a PANLAR, o protocolo Biobadaser foi utilizado como modelo para a implementacao de um novo registro no nosso pais. Durante os dois primeiros anos desse esforco, o protocolo original foi adaptado, traduzido e apresentado a todos os reumatologistas brasileiros. Durante dez meses, dados de 1.037 pacientes (750 tratados com biologicos 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 exposicao total a biologicos foi 2.101 pacientes-ano. A razao mais comum para suspensao da droga foi ineficiencia ou perda de efetividade (50%), e 30% dos pacientes interromperam o tratamento devido a eventos adversos. Tres casos de tuberculose foram observados no grupo biologico, representando maior incidencia do que aquela da populacao brasileira geral. Infeccoes foram observadas em 23% dos pacientes do grupo biologico, sendo o trato respiratorio superior o local mais comumente afetado. Apenas um caso de hanseniase tuberculoide foi observado. Nenhuma morte nem malignidade atribuivel ao efeito dos medicamentos foi observada ate fevereiro de 2010. CONCLUSOES: A implementacao do registro foi bem sucedida. Embora recente, o registro BiobadaBrasil ja forneceu importantes dados.

Pan-American League of Associations for Rheumatology (PANLAR) recommendations and guidelines for musculoskeletal ultrasound training in the Americas for rheumatologists.

Objective:To develop guidelines for Musculoskeletal Ultrasound (MSKUS) training for rheumatologists in the Americas. Methods:A total of 25 Rheumatologists from 19 countries of the American Continent participated in a consensus-based interactive process (Delphi method) using 2 consecutive electronic questionnaires. The first questionnaire included the following: the relevance of organizing courses to teach MSKUS to Rheumatologists, the determination of the most effective educational course models, the trainee levels, the educational objectives, the requirements for passing the course(s), the course venues, the number of course participants per instructor, and the percentage of time spent in hands-on sessions. The second questionnaire consisted of questions that did not achieve consensus (>65%) in the first questionnaire, topics, and pathologies to be covered at each course MSKUS level. Results:General consensus was obtained for MSKUS courses to be divided into 3 educational levels: basic, intermediate, and advanced. These courses should be taught using a theoretical-didactic and hands-on model. In addition, the group established the minimum requirements for attending and passing each MSKUS course level, the ideal number of course participants per instructor (4 participants/instructor), and the specific topics and musculoskeletal pathologies to be covered. In the same manner, the group concluded that 60% to 70% of course time should be focused on hands-on sessions. Conclusion:A multinational group of MSKUS sonographers using a consensus-based questionnaire (Delphi method) established the first recommendations and guidelines for MSKUS course training in the Americas. Pan-American League of Associations for Rheumatology urges that these guidelines and recommendations be adopted in the future by both national and regional institutions in the American continent involved in the training of Rheumatologists for the performance of MSKUS.

REAL-PANLAR Project for the Implementation and Accreditation of Centers of Excellence in Rheumatoid Arthritis Throughout Latin America: A Consensus Position Paper From REAL-PANLAR Group on Improvement of Rheumatoid Arthritis Care in Latin America Establishing Centers of Excellence.

ObjectiveA consensus meeting of representatives of 16 Latin American and Caribbean countries and the REAL-PANLAR group met in the city of Bogota to provide recommendations for improving quality of care of patients with rheumatoid arthritis (RA) in Latin America, defining a minimum standards of care and the concept of center of excellence in RA. MethodsTwenty-two rheumatologists from 16 Latin American countries with a special interest in quality of care in RA participated in the consensus meeting. Two RA Colombian patients and 2 health care excellence advisors were also invited to the meeting. A RAND-modified Delphi procedure of 5 steps was applied to define categories of centers of excellence. During a 1-day meeting, working groups were created in order to discuss and validate the minimum quality-of-care standards for the 3 proposed types of centers of excellence in RA. Positive votes from at least 60% of the attending leaders were required for the approval of each standard. ResultsTwenty-two opinion leaders from the PANLAR countries and the REAL-PANLAR group participated in the discussion and definition of the standards. One hundred percent of the participants agreed with setting up centers of excellence in RA throughout Latin America. Three types of centers of excellence and its criteria were defined, according to indicators of structure, processes, and outcomes: standard, optimal, and model. The standard level should have basic structure and process indicators, the intermediate or optimal level should accomplish more structure and process indicators, and model level should also fulfill outcome indicators and patient experience. ConclusionsThis is the first Latin American effort to standardize and harmonize the treatment provided to RA patients and to establish centers of excellence that would offer to RA patients acceptable clinical results and high levels of safety.

Ultrasound power Doppler synovitis is associated with plasma IL-6 in established rheumatoid arthritis.

BACKGROUND AND OBJECTIVE Cytokines have an important role in the pathogenesis of rheumatoid arthritis (RA). Although plasma levels of IL-6 have been related to musculoskeletal ultrasound (MSUS) synovitis in early DMARD-naïve RA, there are no similar studies in established disease. METHODS 64 RA patients treated with non-biological DMARDs and 30 healthy controls were included in this prospective cross-sectional study. A blood sample was taken before evaluation of disease activity (DAS28) and ultrasonography (all tests performed in a blinded fashion). MSUS was performed by one of two ultrasound-trained rheumatologists on 10 joints of both hands. Gray scale (GS) and pD (power Doppler) synovitis were evaluated using a semi-quantitative scale (0-3) in individual joints, and their sum (score 10) was calculated. Plasma cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN-γ, and VEGF) were quantified by flow cytometry. RESULTS Levels of all cytokines, excepting VEGF, were significantly higher in RA patients than in controls (P⩽0.05). In RA patients, IL-6, but not other cytokines, correlated positively with DAS28 and swollen joint count (P⩽0.01), as well as with 10-joint pD score, and GS and pD of both wrists (P<0.01 for all tests). In multiple linear regression, the association of IL-6 with 10-joint pD score was maintained even after adjustment for DAS28. However, there was no correlation of IL-6 with tender joint count, 10-joint GS score, or presence of erosions. CONCLUSION We demonstrated an association of inflammatory findings on MSUS and plasma IL-6 independently of DAS28 in established RA.

High specificity but low sensitivity of the cartilage oligomeric matrix protein (COMP) test in rheumatoid arthritis and osteoarthritis.

The thrombospondins (TSP) are a family of extracellular proteins involved in tissue genesis and remodeling. The cartilage oligomeric matrix protein (COMP), also known as (TSP-5), is expressed in cartilage, tendon, vitreous, and vascular smooth muscle cells (1). Serum COMP may predict joint damage in rheumatoid arthritis (RA) (2). Increased serum COMP was reported in osteoarthritis (OA), and after cartilage injury (3). In this study, we evaluated serum concentrations of COMP in patients with RA and OA. We also evaluated the diagnostic performance of the COMP test. Sixty-three patients with RA, 40 patients with OA and 100 healthy controls were evaluated. Cases were selected from a database and authorized biobank with diagnosis according to classical criteria for RA (4) and OA (5). Both groups of patients were receiving regular treatment from our outpatient clinics. The control group comprised blood donors 40 years old and above, with no rheumatic complaints. Each patient, or his legal representative, provided written informed consent. Serum COMP was assayed by ELISA (COMP ELISA AnaMar Medical , Lund, Sweden). Concentrations above 12 U/L were considered significant (6). Group comparisons were performed by variance analysis. To estimate the grade of association of serum COMP with disease, odds ratios (OR) were calculated. Diagnostic performance of the COMP assay was evaluated by calculating sensitivity, specificity, and likelihood ratios (LRs). Females predominated in the RA (81%) and OA (88%) populations as compared to controls (45%) (p-0.05). The

Incidence of tuberculosis among patients with rheumatoid arthritis using TNF blockers in Brazil: data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas – BiobadaBrasil)

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 Fishers 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.

Recomendações para a proteção da privacidade do paciente

Concerns regarding the bioethical aspects of the privacy of the individual and the confidentiality of their medical treatment data is increasing in the medical community. The current preliminary clinical and therapeutic processes require the multidisciplinary involvement of a number of individuals, especially in the case of hospitalization. The transmission and storage of clinical and laboratory patient information involves different media, with inherent problems of accessibility and protection of information. The authors describe hypothetical situations that exemplify issues commonly addressed in the work of a clinical bioethics committee, contextualizing these problems in Brazil and globally, and suggest steps to minimize potential problems of the breaching of privacy and confidentiality.

Ultrasound and its clinical use in rheumatoid arthritis: where do we stand?

High-resolution musculoskeletal ultrasound (MSUS) has been increasingly employed in daily rheumatological practice and in clinical research. In rheumatoid arthritis (RA), MSUS can be now considered a complement to physical examination. This method evaluates synovitis through gray-scale and power Doppler and it is also able to identify bone erosions. The utilization of MSUS as a marker of RA activity has received attention in recent literature. Current data account for good correlation of MSUS with classical measures of clinical activity; in some instances, MSUS appears to perform even better. Diagnosis of subclinical synovitis by MSUS might help the physician in RA management. With some variation, interobserver MSUS agreement seems excellent for erosion and good for synovitis. However, lack of MSUS score standardization is still an unmet need. In this review, we describe several MSUS scores, as well as their correlation with clinical RA activity and response to therapy. Finally, we look at the relationship of MSUS with synovial tissue inflammation and discuss future perspectives for a better interpretation and integration of this imaging method into clinical practice.

Paget’s Disease of Bone

Paget’s disease is a chronic disorder characterised by increased resorption and deposition of bone mass, causing various skeletal deformities. It is the second most common bone disorder, following osteoporosis. It is manifested by excessive resorption of bone by osteoclasts and subsequent secondary increase of osteoblast activity. As a result the normal bone tissue is gradually replaced by vascular connective tissue, resulting in a thickened, disorganised trabecular pattern of bone which is of lower quality and has a decreased mechanical resistance. The disease, also known as osteitis deformans, was first described by the English pathologist Sir James Paget, at the end of the nineteenth century [1].