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.

Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: results from two phase 3 studies.

BACKGROUND: The objective of this post-hoc analysis was to assess the efficacy and safety of upadacitinib in psoriatic arthritis (PsA) patients with axial involvement. METHODS: Post-hoc analysis of SELECT-PsA 1 and SELECT-PsA 2 in patients randomized to upadacitinib 15 mg (UPA15), placebo (switched to UPA15 at week 24), or adalimumab 40 mg (ADA; SELECT-PsA 1 only). Axial involvement was determined by investigator judgement (yes or no; based on the totality of available clinical information, such as duration and characteristics of back pain, age of onset, and previous lab investigations and imaging, if available) alone, or investigator judgement and patient-reported outcome (PRO)-based criteria (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4 and BASDAI Q2 ≥ 4). Efficacy outcomes that describe axial disease activity, including BASDAI endpoints, such as change from baseline in the overall BASDAI score or proportion of patients achieving BASDAI50 (≥ 50% improvement from baseline), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints, such as mean change from baseline in overall ASDAS or proportion of patients achieving ASDAS inactive disease or low disease activity, were evaluated at weeks 12, 24, and 56, with nominal P-values shown. Treatment-emergent adverse events (TEAEs) are summarized through week 56. RESULTS: 30.9% of patients in SELECT-PsA 1 and 35.7% in SELECT-PsA 2 had axial involvement by investigator judgement alone; 22.6% (SELECT-PsA 1) and 28.6% (SELECT-PsA 2) had axial involvement by investigator judgement and PRO-based criteria. Greater proportions of patients achieved BASDAI50 with UPA15 versus placebo using either criterion, and versus ADA using investigator judgement alone, at week 24 in SELECT-PsA 1 (investigator alone: UPA15, 59.0%, placebo, 26.9%, P < 0.0001, ADA, 44.1%, P = 0.015; investigator and PRO-based: UPA15, 60.4%, placebo, 29.3%, P < 0.0001, ADA, 47.1%, P = 0.074), with comparable findings in SELECT-PsA 2. Similar results were observed with UPA15 for additional BASDAI and ASDAS endpoints at weeks 12 and 24, with improvements maintained at week 56. Rates of TEAEs were generally similar across sub-groups irrespective of axial involvement status. CONCLUSIONS: PsA patients with axial involvement determined by predefined criteria showed greater BASDAI and ASDAS responses with UPA15 versus placebo, and numerically similar/greater responses versus ADA. Safety results were generally comparable between patients with or without axial involvement. TRIAL REGISTRATION: ClinicalTrials.gov: SELECT-PsA 1, NCT03104400; SELECT-PsA 2, NCT0310437.

Management of Enthesitis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Enthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA. METHODS: We performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies. RESULTS: We included 41 randomized clinical trials in our review and graded each intervention. CONCLUSION: Several classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.

Clinical Specialty Setting as Determinant of Management of Psoriatic Arthritis: A Cross-Sectional Brazilian Study.

OBJECTIVE: The aim of this study was to examine the effect of clinical specialty setting on the management of psoriatic arthritis (PsA) as well as disease activity/burden in Brazil. METHODS: This study is a post hoc analysis of the Brazilian population in a cross-sectional, observational study conducted in 17 countries. Patients were 18 years or older with suspected or confirmed PsA attending routine visits at participating sites. Primary end points were time from symptom onset to PsA diagnosis, from diagnosis to first conventional systemic disease-modifying antirheumatic drug (DMARD) or first biologic DMARD, and from first conventional systemic DMARD to first biologic DMARD. Potential associations were assessed using the Student t test or the Mann-Whitney U nonparametric test. Normality was tested using the Shapiro-Wilk and Kolmogorov-Smirnov tests. For qualitative variables, the χ2 test was adopted. RESULTS: Patients (n = 130) visited dermatology (n = 75) or rheumatology (n = 55) sites. All primary end points were similar between the 2 settings; however, dermatology patients had significantly greater enthesitis counts (2.1 vs 0.6; p = 0.002), absenteeism at work (Work Productivity and Activity Impairment, 19.7% vs 5.2%; p = 0.03), and pain (Health Assessment Questionnaire-Disability Index pain scale, 1.39 vs 1.01; p = 0.032), as well as worse quality of life related to psoriasis (Dermatology Life Quality Index total score, 8.5 vs 5.0; p = 0.019) and mental health (12-item Short-Form Health Survey, version 2.0 subscale, 42.4 vs 47.4; p = 0.029). CONCLUSIONS: In Brazil, PsA disease burden and disease activity were influenced by clinical specialty. Irrespective of setting, patients experienced a delay in being diagnosed with PsA, reinforcing the need for collaborative management of PsA by rheumatologists and dermatologists for better outcomes in these patients.

Patient-Reported Outcomes in Psoriatic Arthritis Patients with an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drugs: SELECT-PsA 2.

INTRODUCTION: Psoriatic arthritis (PsA) has a major impact on health-related quality of life (HRQOL) and other patient-reported outcomes (PROs), important components in the assessment of therapeutic efficacy. We evaluated the impact of upadacitinib on PROs in PsA patients with inadequate responses or intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARD-IR). METHODS: Patients enrolled in the phase 3 SELECT-PsA 2 randomized controlled trial (RCT) received 56 weeks of oral upadacitinib 15 mg QD, upadacitinib 30 mg QD, or placebo switched to either dose of upadacitinib at week 24. PROs included patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI), health-related quality of life (SF-36 physical (PCS) and mental (MCS) component summary and domain scores), fatigue (FACIT-F), psoriasis symptom severity (SAPS), and work productivity (WPAI). Mean changes from baseline in PROs, improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values, and maintenance of improvements were assessed. RESULTS: At weeks 12 and 24, patients treated with either upadacitinib dose reported statistically and nominally significant improvements from baseline across all PROs versus placebo (p ≤ 0.05), except the WPAI absenteeism domain, which were maintained or further improved to week 56. A significantly greater proportion of patients receiving either upadacitinib dose reported improvements ≥ MCID and scores ≥ normative values versus placebo (nominal p ≤ 0.01) in most PROs at weeks 12 and 24, with clinically meaningful improvements continuing to week 56. Improvements ≥ MCID were reported as early as week 2 in PtGA, pain, and HAQ-DI. CONCLUSIONS: Upadacitinib provides rapid, clinically meaningful, and sustained improvements in PROs reported by bDMARD-IR PsA patients. SELECT-PsA 2 ClinicalTrials.gov number, NCT03104374.

Validation and clinical interpretability of PsAID - psoriatic arthritis impact of disease.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease of widely varying presentation, which determines functional and psychological impairment, with a high negative impact on patients' quality of life. Therefore, knowing the patient's perception of their health status is of fundamental importance for understanding the real impact of PsA. Given this context, the European League Against Rheumatism (EULAR) recently developed the Psoriatic Arthritis Impact of Disease (PsAID) - instrument to specifically assess the impact of PsA for the patient. OBJECTIVE: Validate the brazilian portuguese version of PsAID-12 (Psoriatic Arthritis Impact of Disease) and to verify its interpretability in clinical practice, through its relation with measures of psoriatic arthritis activity. METHODS: A multicenter cross-sectional study, which recruited 160 patients, who met the Classification criteria for Psoriatic Arthritis (CASPAR), in six Brazilian centers of rheumatology. Reliability was assessed by Cronbach's alpha coefficient and by the intraclass correlation coefficient (ICC). The construct validity was evaluated by exploratory factorial analysis and also by Spearman correlation with other PROMs and measures of disease activity evaluation. RESULTS: Of the total number of participants, 50% were female, with a mean age (SD) of 54.0 ± 11.2 years; 68% had only peripheral arthritis and 32% had pure or mixed axial involvement. The majority (67.7%) of the patients were using biological treatment. The reliability of internal consistency (alpha-Cronbach = 0.93) and test-retest (ICC = 0.996) were good. Factor analysis revealed two factors, named physical and psychosocial, which included the skin evaluation item. PsAID-12 correlated significantly with other PROMs, demonstrating good construct validity. PsAID-12 was also significantly associated with the disease activity assessment instruments (DAS28-ESR, ASDAS, and BASDAI) and the MDA status: "Minimum Disease Activity". Fibromyalgia did not significantly affect the final PsAID-12 score. CONCLUSION: The brazilian version of PsAID-12 has been shown to be a reliable and valid measure of the impact of the disease in patients with psoriatic arthritis. Moreover, it associated significantly with the scores of disease activity assessment.

Treatment Mode Preferences in Psoriatic Arthritis: A Qualitative Multi-Country Study.

OBJECTIVE: Qualitative research exploring patient preferences regarding the mode of treatment administration for psoriatic arthritis (PsA) is limited. We report patient preferences and their reasons across PsA treatment modes. METHODS: In this global, cross-sectional, qualitative study, interviews were conducted with adult patients with PsA in Brazil, France, Germany, Italy, Spain, the UK, and the US. Patients were currently taking a disease-modifying antirheumatic drug (DMARD). Patients indicated the order and strength of preference (0-100; 100 = strongest) across four modes of treatment administration: oral (once daily), self-injection (weekly), clinic injection (weekly), and infusion (monthly); reasons for preferences were qualitatively assessed. Descriptive statistics were reported. Fisher's exact tests and t-tests were conducted for treatment mode outcomes. RESULTS: Overall, 85 patients were interviewed (female, 60.0%; mean age, 49.8 years). First-choice ranking (%) and mean [standard deviation] preference points were: oral (49.4%; 43.9 [31.9]); self-injection (34.1%; 32.4 [24.8]); infusion (15.3%; 14.5 [20.0]); clinic injection (1.2%; 9.2 [10.0]). Of 48 (56.5%) patients with a strong first-choice preference (ie point allocation ≥60), 66.7% chose oral administration. Self-injection was most often selected as second choice (51.8%), clinic injection as third (49.4%), and infusion as fourth (47.1%). Oral administration was the first-choice preference in the US (88.0% vs 38.0% in Europe). The most commonly reported reason for oral administration as the first choice was speed and ease of administration (76.2%); for self-injection, this was convenience (75.9%). The most commonly reported reason for avoiding oral administration was concern about possible drug interactions (63.6%); for self-injection, this was a dislike of needles or the injection process (66.7%). CONCLUSION: Patients with PsA preferred oral treatment administration, followed by self-injection; convenience factors were common reasons for these preferences. Overall, 43.5% of patients did not feel strongly about their first-choice preference and may benefit from discussions with healthcare professionals about PsA treatment administration options.

Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloarthritis on Biologic Drugs-Data From the Brazilian Registry for Biologics Monitoring.

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.

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.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

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.

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 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.

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.

Drug survival and causes of discontinuation of the first anti-TNF in ankylosing spondylitis compared with rheumatoid arthritis: analysis from BIOBADABRASIL.

Treatment survival with biological therapy may be influenced by many factors, and it seems to be different among various rheumatic diseases and biological agents. The goal of the study was to compare the drug survival and the causes of discontinuation of anti-tumoral necrosis factor (anti-TNF) therapy in ankylosing spondylitis (AS) with rheumatoid arthritis (RA). Study participants were a cohort from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (BIOBADABRASIL) between 2008 and 2012. The observation time was up to 4 years following the introduction of the first treatment. Gender, age, disease duration, disease activity, comorbidities, and concomitant therapies were assessed. A total of 1303 patients were included: 372 had AS and 931 had RA in which 38.7 % (n = 504) used infliximab (IFX), 34.9 % (n = 455) used adalimumab (ADA), and 26.4 % (n = 344) used etanercept (ETA). The anti-TNF drug survival of patients with AS was 63.08 months (confidence interval (CI) 60.24, 65.92) and patients with RA was 47.5 months (CI 45.65, 49.36). It was significant higher in AS (log-rank; p ≤ 0.001). Patients with RA discontinued anti-TNF more than patients with AS when adjusted to gender and corticosteroid. The adjHR (95 % CI) was 1.6 (1.14, 2.31). Female patients who were also corticosteroid users, but not of advanced age, have shown lower survival for both diseases (log-rank, p ≤ 0.001). The discontinuation rate of IFX, but not of ADA or ETA, was significantly higher in RA than in SA; HR (95 % CI) was 2.49 (1.46, 4.24). The main causes of discontinuation were ineffectiveness and adverse event in both diseases. AS patients have better drug survival adjusted to gender, age, and corticosteroid. This results appear to be related to the disease mechanism.

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.

Drug therapies for peripheral joint disease in psoriatic arthritis: a systematic review.

In 2009, GRAPPA published their first evidence-based recommendations for the treatment of psoriasis and psoriatic arthritis (PsA). Since then, new information has been published and drugs developed. We summarize evidence for the efficacy of available treatments for peripheral joint involvement in PsA. We performed a systematic review of current literature on the efficacy of different therapies, management, and therapeutic strategies for peripheral arthritis involvement in PsA, in order to provide information for the development of the new GRAPPA treatment recommendations.

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.