Roberto Ranza

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project)

Objective To develop new composite disease activity indices for psoriatic arthritis (PsA). Methods Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). Results 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index >10) both nonparametric and AUC curve statistics were nonsignificant for all measures. Conclusions Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

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.

Recomendações sobre diagnóstico e tratamento da espondilite anquilosante

Descricao do metodo de elaboracao das evidencias Os integrantes da Comissao de Espondiloartrites da Sociedade Brasileira de Reumatologia (bienio 2010-2012) participaram do Curso de Elaboracao de Evidencias da Associacao Medica Brasileira, em Sao Paulo, durante o primeiro semestre de 2011. As questoes foram concluidas em reuniao presencial da Comissao de Espondiloartrites no dia 15 de outubro de 2011, durante a XVIII Jornada Cone Sul de Reumatologia, em Florianopolis (SC, Brasil), e foram posteriormente aprovadas por todos os coordenadores do Registro Brasileiro de Espondiloartrites. As 15 questoes clinicas consideradas relevantesforam estruturadas por meio da estrategia do P.I.C.O. (Paciente; Intervencao ou Indicador; Comparacao; Outcome). As estrategias de busca avaliaram as bases de dados MEDLINE, EMBASE, Scielo/Lilacs, Cochrane Library ate fevereiro de 2012 (Apendice). Os artigos selecionados na primeira estrategia de busca foram submetidos a avaliacao critica das evidencias, utilizando-se o escore de Jadad. Posteriormente, foram elaboradas as respostas das recomendacoes – cada referencia bibliografica selecionada apresentava o correspondente grau de recomendacao e forca de evidencia cientifica. Para as recomendacoes finais, as referencias bibliograficas foram atualizadas ate agosto de 2012, redigidas em texto unico pelo coordenador, e submetidas aos coautores em dois turnos, para elaboracao do texto final. Grau de recomendacao e forca de evidencia A: Estudos experimentais e observacionais de melhor consistencia. B: Estudos experimentais e observacionais de menor consistencia. C: Relatos de casos (estudos nao controlados). D: Opiniao desprovida de avaliacao critica, baseada em consensos, estudos fisiologicos ou modelos animais. Objetivo Estabelecer as recomendacoes para o manejo (criterios classificatorios e avaliacao por ressonância magnetica e genetica) das espondiloartrites e para o tratamento da espondilite anquilosante.

Prevalence of Psoriatic Arthritis in a Large Cohort of Brazilian Patients with Psoriasis

Objective. To determine the prevalence of psoriatic arthritis (PsA) in a large cohort of Brazilian patients with psoriasis (PsO) being seen at dermatology centers. Methods. A multicenter study was conducted in 4 university dermatology clinics. In each center, consecutive patients with confirmed diagnoses of PsO were evaluated by a rheumatologist. Individuals were classified as having PsA according to the ClASsification criteria for Psoriatic ARthritis (CASPAR). Laboratory tests and radiographs were performed, as needed, based on the clinical judgment of the rheumatologist. Results. A total of 524 patients with PsO were evaluated. The mean age was 48.5 ± 14.5 years, 50% were women, and the mean PsO duration was 15.4 ± 11.7 years. A diagnosis of PsA was documented in 175 patients (33%), of whom 49% were newly identified by the rheumatologist. Most individuals with PsA (72%) had peripheral involvement, 11% had isolated axial involvement, and 17% had both peripheral and axial involvement. Dactylitis occurred in 20% and clinical enthesitis in 30% of the patients. Laboratory and/or radiograph tests were necessary for a definitive diagnosis of PsA in 42 of 175 individuals (24%). Conclusion. In our study, one-third of Brazilian patients with PsO, followed in dermatology settings, were diagnosed with PsA by a rheumatologist. Almost half of subjects with PsA had no previous diagnosis. A collaboration between dermatologists and rheumatologists is greatly needed to establish earlier PsA diagnoses and adequate multidisciplinary management.

Conceitos atuais e relevantes sobre artrite psoriásica

Psoriatic arthritis (PsA) is a systemic, polymorphic joint disease with variable presentation and clinical course. The outcome depends on the association with severe comorbidities such as diabetes, hypertension and dyslipidemia. Early diagnosis requires a high degree of clinical suspicion, especially when skin manifestations are subtle and poorly defined. Progressive erosive disease can occur in up to half of patients, associated with anatomical and functional changes in about 20%. Thus, the prognosis of PsA remains unclear, especially if diagnosis and treatment are delayed. Based on extensive literature review (PubMed and Lilacs) and experience of our services, new concepts of immunogenetics, pathophysiology, and clinical and therapeutic aspects are discussed. Factors that reduce the quality of life and life expectancy of patients, as well as new guidelines for treatment, will be emphasized. Control of inflammation, especially in enthesitis and axial forms of PsA, was made possible due to the introduction of anti-TNF biologics. Finally, the role of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) should be emphasized, since it promotes meetings and joint studies between rheumatologists and dermatologists to provide scientific evidence for the sweeping changes in clinical management and treatment of patients with PsA

Recommendations for the management and treatment of ankylosing spondylitis

Description of the method used for evidence preparation The members of the Comissao de Espondiloartrites da Sociedade Brasileira de Reumatologia (Commission on Spondyloarthritis of the Brazilian Society of Rheumatology, SBR) 2010–2012 took part in the Evidence Preparation Course given by the Associacao Medica Brasileira (Brazilian Medical Association, AMB) in Sao Paulo in the first semester of 2011. The questions were finally concluded at a meeting of the Commission on Spondyloarthritis held on 15 October 2011 in Florianopolis (SC, Brazil), during the 18th Southern Cone Rheumatology Meeting and were later approved by all the coordinators of the Brazilian Spondyloarthritis Registry. The 15 clinical questions considered to be relevant were structured using the P.I.C.O. method (patient; intervention or indicator; comparison; outcome). The literature search was conducted by searching the databases MEDLINE, EMBASE, SciElo/Lilacs, and the Cochrane Library through February, 2012 (Appendix). Critical assessment of the evidence in the selected articles was performed using the Jadad score. Next, the answers to the questions included in the Recommendations were elaborated, and all the selected references exhibit the corresponding grade of recommendation and strength of scientific evidence. The references were updated through August, 2012, entered into a single file by the coordinator, and sent to the co-authors in two successive rounds for preparation of the final version. Grades of recommendation and strength of evidence A: Most consistent experimental and observational studies. B: Less consistent experimental and observational studies. C: Case reports (uncontrolled studies). D: Opinion that is not substantiated by critical evaluation, based on consensus, physiological studies or animal models. Objective To establish recommendations for the management (classification and evaluation criteria by magnetic resonance and genetics) of spondyloarthritis and for the treatment of ankylosing spondyloarthritis.

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.

Hiperperfusão no território orbital de gestantes portadoras de lúpus eritematoso sistêmico

PURPOSE to analyze the ophthalmic artery functioning in pregnant women with systemic lupus erythematosus (PL) without active renal disease as compared to non-pregnant women with lupus (NPL) without active renal disease, and to normal pregnant women (PN). METHODS observational study that analyzed ophthalmic artery dopplervelocimetric variables of 20 PN, 10 PL and 17 NPL women. The variables analyzed were: pulsatility index (PI), final diastolic velocity (FDV) and velocity peak ratio (VPR). Mean and standard deviation of these indexes were calculated. For group mean comparison, analysis of variance (ANOVA) and the post-hoc Tukey test have been used, with confidence interval of 95% (p<0.05). RESULTS the PN group showed the following means and standard deviations of ophthalmic artery parameters: PI=2,4+/-0,3; VPR=0,5+/-0,1 e FDV=5,1+/-2,1 cm/s. The PL and NPL groups showed the following values, respectively: PI=2,0+/-0,4 and 1,9+/-0,4; VPR=0,6+/-0,1 and 0,6+/-0,1; FDV=9,7+/-3,9 cm/s and 8,1+/-4,3 cm/s. There was not significant mean difference between the PL and NPL groups for PI, VPR or FDV. However, statistically significant mean differences were observed between PN and PL for PI, VPR and FDV, with higher values of FDV and VPR in the PL group. CONCLUSIONS there was a reduction of ophthalmic artery vascular impedance with orbital hyperfusion in the two groups of women with lupus erythematosus as compared to normal pregnant women. These results may help to improve the understanding on pathophysiology of systemic lupus erythematosus. In addition, the present method may be applied in future studies as a complementary procedure for the differential diagnosis between pre-eclampsia and renal failure due to lupus.

Semantic and psychometric validation of the Brazilian Portuguese version (PASE-P) of the Psoriatic Arthritis Screening and Evaluation questionnaire

PASE (Psoriatic Arthritis Screening and Evaluation) was developed in the English language to screen for inflammatory arthritis among patients with psoriasis. It is 15 item self administered questionnaire with a score from 15 to 75. A higher score indicates a greater risk for inflammatory joint disease. The purpose of this study was to translate, adapt and validate this questionnaire into Brazilian Portuguese (PASE-P). METHODS: 465 patients diagnosed with psoriasis (158 with psoriatic arthritis confirmed by a rheumatologist according to the CASPAR criteria and 307 without) were evaluated in dermatology clinics. We performed the analysis of semantic equivalence in eight steps. For psychometric equivalence, we evaluated the data quality, reliability, construct validity, well-known groups and discriminant characteristics of the items, as well as a ROC curve to determine optimal PASE-P cutoff points in case identification and their sensitivity / specificity. The final version presented excellent reproducibility (CCI = 0.97) and reliability (Cronbach’s alpha> 0.9). A cut-off point of 25 distinguished between patients with and without psoriatic arthritis, with sensitivity of 69.5 and specificity of 86.8. PASE-P proved to be culturally valid and reliable to screen for psoriatic arthritis in Brazilian patients with psoriasis.

AB0232 Disease activity state in patients with rheumatoid arthritis included in the biobadabrasil registry

Objectives to analyse disease activity of RA patients at the start of treatment with a biologic agent (adalimumab, infliximab, certolizumab, etanercept, golimumab, abatacept, rituximab and tocilizumab -bDMARDs), target (tofacitinib-tsDMARDs) therapy or conventional DMARDs (comparison cohort of RA patients – csDMARDs). Methods BiobadaBrasil is a prospective observational cohort study, part of an international initiative (biobadaAmerica) in collaboration with BiobadaSeR; established in 2009, is an ongoing study supported by the Brazilian Society of Rheumatology (29 public centres located at academic instituitions and 2 in private practice) focused on the study of adverse events in patients on biologic therapy. Additionally, by decision of its investigators, disease activity scores were also recorded at the beginning of each treatment. Sex, age, disease duration, RA -DAS-28, concomitant treatments at baseline were collected. Results expressed in mean ±SD,%(n) Results -Data from 1984 RA patients (67% on ts/bDMARDs) were analysed: 86% of the patients were women; mean age=56.6±14.95 years; disease duration=14.4±9.42; 87% RF positive. There were 3802 treatment courses, 67% with aTNF (Adalimumab-ADA, Certolizumab-CTZ, Etanercept-ETA, Golimumab-GOL, Infliximab-INFL), 33% non-aTNF (Abatacept-ABA, Rituximab-RIT, Tocilizumab-TCL) including Tofacitinib-TOF. The table 1 below depicted the medications prescribed at the initiation of a new treatment course:Abstract AB0232 – Table 1 n courses ADA(855) CTZ(85) ETA(708) GOL(113) INFL(772) ABA(163) RIT(184) TCL(192) TOF(70) cDMARDs(660) DAS28 5.1±1.6 4.9±1.5 5.1±1.6 4.9±1.7* 5.3±1.6 5.3±1.4 5.3±1.6 5.4±1.4* 5.3±1.3 5.2±2.8 CE (%) 58 76 60 61 58 68 74 71 83 78 MTX (%) 55 57 53 56 59 54 51 62 49 83 LFN (%) 27 42 27 31 23 31 25 18 27 45 Chlor (%) 14 15 11 10 15 11 19 17 11 30 Considering the more recent medications patients beginning TCL have more active disease than the ones beginning GOL and CTZ (p<0,006); anti-TNF are prescribed in association with MTX in less than 60% of the treatments. Extensive use of corticosteroids was identified besides consistent use of leflunomide and of hydroxychloroquine. Starting of new treatments was related to moderate/high levels of disease activity. Conclusions patterns of bDMARDS, csDMARDS and corticosteroid use clearly surfaced. Possibilities of improvement can be addressed. Acknowledgements for data monitoring P Cabral; contributing to BiobadaBrasil registry, R. Giorgi, H. Pereira, M. Scheinberg, F. Sztajnbok, W. Vieira Disclosure of Interest None declared