Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials.

OBJECTIVE: We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA). METHODS: This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs. RESULTS: A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled. CONCLUSION: Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Open Access Pan American League of Associations for Rheumatology recommendations for the treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.

Enthesitis and Dactylitis Resolution with Risankizumab for Active Psoriatic Arthritis: Integrated Analysis of the Randomized KEEPsAKE 1 and 2 Trials.

INTRODUCTION: The presence (vs absence) of enthesitis/dactylitis is associated with greater psoriatic arthritis (PsA) activity and reduced health-related quality of life. Risankizumab, an interleukin 23 antagonist, demonstrated superior treatment efficacy over placebo in patients with PsA, including enthesitis/dactylitis. Herein, we report the efficacy of risankizumab on complete resolution of enthesitis and/or dactylitis and improvements in patient-reported outcomes in patients with PsA. METHODS: This integrated post hoc analysis of data from KEEPsAKE 1 and KEEPsAKE 2 included patients with baseline enthesitis (Leeds Enthesitis Index > 0) and/or dactylitis (Leeds Dactylitis Index > 0). Efficacy outcomes at weeks 24 and 52 included proportion of patients achieving enthesitis and/or dactylitis resolution and minimal clinically important differences (MCID) in pain, Health Assessment Questionnaire-Disability Index, and Functional Assessment of Chronic Illness Therapy-Fatigue. RESULTS: Of 1407 patients, approximately 63%, 28%, and 20% had baseline enthesitis, dactylitis, and both enthesitis/dactylitis, respectively. At week 24, higher response rates were observed for risankizumab vs placebo for resolution of enthesitis, dactylitis, and both enthesitis/dactylitis (differences of 13.9%, 16.9%, and 13.3%, respectively; p < 0.05). By week 52, risankizumab treatment resulted in complete resolution of enthesitis, dactylitis, and both enthesitis and dactylitis in 55.0%, 76.1%, and 52.3% of patients; similar resolution rates occurred among patients who switched from placebo to risankizumab. Among risankizumab-treated patients who achieved resolution of enthesitis and/or dactylitis, MCIDs were also attained in patient-reported pain, disability, and fatigue at week 24 (all p < 0.05; except fatigue in patients with resolution of both enthesitis/dactylitis); responses were sustained through week 52. CONCLUSIONS: Higher proportions of risankizumab-treated (vs placebo-treated) patients achieved enthesitis and/or dactylitis resolution and meaningful improvements in patient-reported outcomes at week 24 and generally sustained responses at week 52. Thus, risankizumab may result in sustained alleviation of PsA-related pathognomonic musculoskeletal lesions of enthesitis/dactylitis. GOV IDENTIFIERS: NCT03675308, and NCT03671148.

Pan American League of Associations for Rheumatology Recommendations for the Treatment of Psoriatic Arthritis.

OBJECTIVE: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. RESULTS: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. CONCLUSION: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.

Esophageal manometry in systemic sclerosis: findings and association with clinical manifestations

SUMMARY INTRODUCTION Systemic sclerosis (SSC) is an autoimmune disorder that affects several organs of unknown etiology, characterized by vascular damage and fibrosis of the skin and organs. Among the organs involved are the esophagus and the lung. OBJECTIVES To relate the profile of changes in esophageal electromanometry (EM), the profile of skin involvement, interstitial pneumopathy (ILD), and esophageal symptoms in SSC patients. METHODS This is an observational, cross-sectional study carried out at the SSC outpatient clinic of the Hospital de Clínicas of the Federal University of Uberlândia. After approval by the Ethics Committee and signed the terms of consent, 50 patients were initially enrolled, from 04/12/2014 to 06/25/2015. They were submitted to the usual investigations according to the clinical picture. The statistical analysis was descriptive in percentage, means, and standard deviation. The Chi-square test was used to evaluate the relationship between EM, high-resolution tomography, and esophageal symptoms. RESULTS 91.9% of the patients had some manometric alterations. 37.8% had involvement of the esophageal body and lower esophageal sphincter. 37.8% had ILD. 24.3% presented the diffuse form of SSC. No association was found between manometric changes and clinical manifestations (cutaneous, pulmonary, and gastrointestinal symptoms). CONCLUSION The present study confirms that esophageal motility alterations detected by EM are frequent in SSC patients, but may not be related to cutaneous extension involvement, the presence of ILD, or the gastrointestinal complaints of patients.

RESUMO INTRODUÇÃO A esclerose sistêmica (ES) é uma doença autoimune que afeta vários órgãos de etiologia desconhecida, caracterizada por dano vascular e fibrose da pele e órgãos. Entre os órgãos envolvidos estão o esôfago e o pulmão. OBJETIVOS Relacionar o perfil das alterações na eletromanometria (ME), o perfil de acometimento da pele, a pneumopatia intersticial (PI) e os sintomas esofágicos em pacientes com ES. MÉTODO Trata-se de um estudo observacional, transversal, realizado no ambulatório de SSC do Hospital das Clínicas da Universidade Federal de Uberlândia. Após aprovação pelo Comitê de Ética e assinatura dos termos de consentimento, 50 pacientes foram inicialmente convidados, de 04/12/2014 a 25/06/2015. Eles foram submetidos às investigações usuais de acordo com o quadro clínico. A análise estatística foi descritiva em porcentagem, média e desvio padrão. O teste Qui-quadrado foi utilizado para avaliar a relação entre ME, tomografia de alta resolução e sintomas esofágicos. RESULTADOS 91,9% dos pacientes apresentaram alterações manométricas. 37,8% tinham envolvimento do corpo esofágico e do esfíncter esofágico inferior. 37,8% tinham IP. 24,3% apresentaram a forma difusa da ES. Não há associação entre alterações manométricas e manifestações clínicas (sintomas cutâneos, pulmonares e gastrointestinais). CONCLUSÃO O presente estudo confirma que as alterações da motilidade esofágica detectadas pela EM são frequentes em pacientes com SSC, mas podem não estar relacionadas ao envolvimento cutâneo, à de DPI ou às queixas gastrointestinais dos pacientes.

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) / Incidência de tuberculose em pacientes com artrite reumatoide em uso de bloqueadores do TNF no Brasil: dados do Registro Brasileiro de Monitoração de Terapias Biológicas BiobadaBrasil

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.

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.

Conceitos atuais e relevantes sobre artrite psoriásica / Current and relevant concepts in psoriatic arthritis

A artrite psoriásica (APs) é uma doença articular sistêmica e polimórfica de apresentação e curso clínico variáveis, associada a comorbidades importantes como diabetes mellitus, hipertensão arterial e dislipidemia. Para o diagnóstico precoce da doença é necessário alto grau de suspeita clínica, sobretudo quando as manifestações cutâneas são sutis e pouco definidas. Doença erosiva progressiva pode ocorrer em até metade dos pacientes, associada a alterações anatômicas e funcionais em cerca de 20 por cento, de modo que o prognóstico da APs permanece obscuro, especialmente se diagnóstico e tratamento forem tardios. Fundamentados em ampla revisão da literatura (PubMed e Lilacs) e experiência dos nossos serviços, novos conceitos de imunogenética, fisiopatologia, aspectos clínicos e terapêuticos serão discutidos. Fatores que reduzem a qualidade e a expectativa de vida dos pacientes e novas diretrizes que norteiam um tratamento mais precoce e efetivo serão enfatizados. O controle do processo inflamatório, especialmente nas formas axiais e entesíticas da APs, tornou-se possível graças à introdução dos medicamentos biológicos anti-TNF. Finalmente, o papel do GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) deve ser ressaltado, já que promove reuniões e estudos conjuntos entre reumatologistas e dermatologistas no sentido de fornecer evidências científicas para as amplas mudanças no manejo clínico e terapêutico de pacientes com APs.

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 percent. 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.

Registro brasileiro de biológicos: processo de implementação e resultados preliminares do BiobadaBrasil / Brazilian biologic registry: BiobadaBrasil implementation process and preliminary results

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 por cento), e 30 por cento 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 por cento 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 percent), while 30 percent 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 percent 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.

Hiperperfusão no território orbital de gestantes portadoras de lúpus eritematoso sistêmico / Orbital territory hyperperfusion in pregnant women with systemic lupus erythematosus

OBJETIVO: analisar o comportamento da artéria oftálmica em grávidas portadoras de lúpus eritematoso sistêmico (GL), sem doença renal em atividade, comparando com não-grávidas com lúpus (NGL), sem doença renal em atividade e grávidas normais (GN). MÉTODOS: estudo observacional que analisou as variáveis doplervelocimétricas da artéria oftálmica de 20 GN, 10 GL e 17 NGL. As variáveis analisadas foram os índices de pulsatilidade (IP), a velocidade diastólica final (VDF) e a razão entre picos de velocidade (RPV). Foram calculadas as médias dos índices e respectivos desvios padrões. Para comparação das médias dos índices dos três grupos, utilizou-se o teste de variância (ANOVA) e prova pós-análise de Tukey, com intervalo de confiança de 95 por cento (p<0,05). RESULTADOS: o grupo de gestante normal apresentou as seguintes médias e desvio padrão dos parâmetros da artéria oftálmica: IP=2,4±0,3; RPV=0,5±0,1 e VDF=5,1±2,1 cm/seg. Já os dois grupos GL e NGL mostraram, respectivamente, as seguintes médias e desvio padrão da artéria oftálmica: IP=2,0±0,4 e 1,9±0,4; RPV=0,6±0,1 e 0,6±0,1; VDF=9,7±3,9 cm/s e 8,1±4,3 cm/s. Não houve diferenças estatísticas significativas quando comparadas as médias do IP, VDF e RPV entre os grupos GL e NGL. Porém, observaram-se diferenças estatísticas significativas entre as médias do IP, VDF e RPV dos grupos GN e GL, com valores mais elevados de VDF e RPV no grupo GL. CONCLUSÕES: houve redução da impedância vascular da artéria oftálmica e hiperperfusão orbital nos dois grupos de pacientes com lúpus em relação às grávidas normais. Os conhecimentos obtidos neste estudo poderão auxiliar no melhor entendimento da fisiopatologia do lúpus eritematoso sistêmico, bem como poderá ser empregado em estudos futuros como método complementar para o diagnóstico diferencial entre a pré-eclâmpsia e a atividade de doença renal nas gestantes com lúpus.

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 percent (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.