Abstract Background There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). Methods The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. Results A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. Conclusions Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population. HLAB27 HLAB HLA B27 B HLA-B2 SpA, , (SpA) worldwide However mixedrace mixed race populations RBE. . (RBE) multicenter observational 4 Brazil follow 1 (1 rheumatologist 2 (2 18 ≥1 years 3 (3 axial protocol historical 109 included 734 73 73.4 444 44 44. ±13.2 132 13 (±13.2 uveitis Conversely psoriasis activity mobility world Furthermore HLAB2 B2 HLA-B (SpA (RBE ( ≥ 10 7 73. ±13. (±13. ±13 (±13 ±1 (±1 ± (±

Abstract Background Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. Methods A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. Results Six recommendations were elaborated regarding the pharmacological treatment of Raynaud’s phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. Conclusion These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice. (SSc manifestations decade (RCTs PatientPopulation Patient Population Patient/Population Intervention Comparison PICO (PICO Assessment GRADE (GRADE methodology recommendation 75 needed Raynauds Raynaud s phenomenon healing (healing ulcers ILD (ILD drugs rituximab placebocontrolled placebo controlled found decisionmaking decision making practice 7

Abstract Background The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. Aim To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database. Methods This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18–60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics - IBGE), and geographic region of residence. Results From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32–4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. Conclusions Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings. HLAB27 HLAB HLA B27 B HLA-B2 14 14% However Brazil crosssectional cross sectional REDOME (REDOME 18–60 1860 18 60 (18–6 old. old . old) selfreported self reported IBGE, IBGE , IBGE) 199 2022 5389143 5 389 143 5,389,14 included 435 4 35 4.35 CI 95 4.32–4.37%, 432437 4.32–4.37% 32 37 4.32–4.37%) 57.2% 572 57 2 (57.2 women 41.7yo. 417yo yo 41.7yo 41 7yo 41.7yo) races 485 85 4.85 Whites 292 92 2.92 Blacks 376 3 76 3.76 Browns ie i e i.e races) 395 3.95 Yellows Brazilians Brazilians) 318 3.18 Indigenous (North 3.62% 362 62 Northeast 3.63% 363 63 Southeast 4.29% 429 29 Midwest 45 4.5 525 25 5.25 South. South South) 132 1 1.32 006 0 06 0.06 colonization slavery flows HLAB2 B2 HLA-B 18–6 186 6 (18– 19 202 538914 38 5,389,1 43 4.3 9 43243 4.32–4.37 57.2 (57. 48 4.8 2.9 7 3.7 39 3.9 31 3.1 3.62 36 3.63 4.29 42 4. 52 5.2 13 1.3 00 0.0 18– (18 20 53891 5,389, 4324 4.32–4.3 57. (57 2. 3. 3.6 4.2 5. 1. 0. (1 5389 5,389 432 4.32–4. (5 ( 538 5,38 4.32–4 53 5,3 4.32– 5, 4.32

Abstract Background Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. Methods Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. Results ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. Conclusion We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698). postacute post acute COVID19 COVID 19 COVID-1 (ARD scarce disease criteria 10 nonARD non SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- RTPCR/antigen RTPCRantigen RT PCR/antigen PCR antigen test vaccine Postacute Post ( 1 sex 58.3% 583 58 (58.3 vs 531 53 53.1% 0.6854 06854 0 6854 39.8% 398 39 8 (39.8 469 46 9 46.9% 0.5419. 05419 0.5419 . 5419 0.5419) COVID19, 19, 54% 54 (54 412 41 41.2% 0.7886, 07886 0.7886 , 7886 0.7886) 68.3% 683 68 (68.3 882 88 88.2% 0.1322. 01322 0.1322 1322 0.1322) reinfection 0.05. 005 0.05 05 0.05) 0.05, immuneinflammatory immune inflammatory population NCT04754698. NCT04754698 NCT (NCT04754698) COVID1 COVID- SARS-CoV RTPCR PCRantigen 58.3 5 (58. 53.1 0.685 0685 685 39.8 (39. 46.9 0541 0.541 541 (5 41.2 0788 0.788 788 68.3 6 (68. 88.2 0132 0.132 132 00 0.0 NCT0475469 (NCT04754698 58. (58 53. 0.68 068 39. (39 46. 054 0.54 41. 078 0.78 78 68. (68 88. 013 0.13 13 0. NCT047546 (NCT0475469 0.6 06 (3 0.5 07 0.7 7 (6 01 0.1 NCT04754 (NCT047546 NCT0475 (NCT04754 NCT047 (NCT0475 NCT04 (NCT047 NCT0 (NCT04 (NCT0 (NCT

Abstract In this paper, we sought to determine the prevalence of arthritis mutilans in a single cohort of Brazilian psoriatic arthritis patients followed at a tertiary university reference center. Our study demonstrated a high prevalence of arthritis mutilans associated to comorbidities and biologic therapy. In addition, our data suggest that axial involvement may be an intriguing aspect of psoriatic arthritis mutilans and that rheumatologists should be aware of axial disease, even if the phenotype is marked by peripheral joint severity.

Abstract Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. Over some decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been the basis for the pharmacological treatment of patients with axial spondyloarthritis (axSpA). However, the emergence of the immunobiologic agents brought up the discussion about the role of NSAIDs in the management of these patients. The objective of this guideline is to provide recommendations for the use of NSAIDs for the treatment of axSpA. A panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of randomized clinical trials for 15 predefined questions. The Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations were used, and at least 70% agreement of the voting panel was needed. Fourteen recommendations for the use of NSAIDs in the treatment of patients with axSpA were elaborated. The purpose of these recommendations is to support clinicians’ decision making, without taking out his/her autonomy when prescribing for an individual patient.

Abstract Psoriatic arthritis (PsA) is a chronic and systemic immune disease characterized by inflammation of peripheral and/ or axial joints and entheses in patients with psoriasis (PsO). Extra-articular and extracutaneous manifestations and numerous comorbidities can also be present. These recommendations replace the previous version published in May 2013. A systematic review of the literature retrieved 191 articles that were used to formulate 12 recommendations in response to 12 clinical questions, divided into 4 sections: diagnosis, non-pharmacological treatment, conventional drug therapy and biologic therapy. These guidelines provide evidence-based information on the clinical management for PsA patients. For each recommendation, the level of evidence (highest available), degree of strength (Oxford) and degree of expert agreement (interrater reliability) are reported.

Abstract Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013. A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed. These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

Abstract Background: The presence of enthesitis is associated with higher disease activity, more disability and incapacity to work and a poorer quality of life in spondyloarthritis (SpA). There is currently no consensus on which clinical score should be used to assess enthesitis in SpA. The objective of the present work was to compare the correlation of three enthesitis indices (MASES, SPARCC and LEI) with measures of disease activity and function in a heterogeneous population of patients with axial and peripheral SpA. Methods: A cross-sectional study was conducted in three Brazilian public university hospitals; patients fulfilling ASAS classification criteria for peripheral or axial SpA were recruited and measures of disease activity and function were collected and correlated to three enthesitis indices: MASES, SPARCC and LEI using Spearman's Correlation index. ROC curves were used to determine if the the enthesitis indices were useful to discriminate patients with active disease from those with inactive disease. Results: Two hundred four patients were included, 71.1% (N = 145) fulfilled ASAS criteria for axial SpA and 28.9% (N = 59) for peripheral SpA. In axial SpA, MASES performed better than LEI (p = 0.018) and equal to SPARCC (p = 0.212) regarding correlation with disease activity (BASDAI) and function (BASFI). In peripheral SpA, only MASES had a weak but statistical significant correlation with DAS28-ESR (rs 0.310 p = 0.05) and MASES had better correlation with functional measures (HAQ) than SPARCC (p = 0.034). Conclusion: In this sample composed of SpA patients with high coexistence of axial and peripheral features, MASES showed statistical significant correlation with measures of disease activity and function in both axial and peripheral SpA.

O tratamento das doenças reumáticas autoimunes sofreu uma progressiva melhora ao longo da última metade do século passado, que foi expandida com a contribuição das terapias biológicas ou imunobiológicos. No entanto, há que se atentar para as possibilidades de efeitos indesejáveis advindos da utilização dessa classe de medicações. A Sociedade Brasileira de Reumatologia (SBR) elaborou um documento, baseado em ampla revisão da literatura, sobre os aspectos relativos à segurança dessa classe de fármacos, mais especificamente no que diz respeito ao tratamento da artrite reumatoide (AR) e das espondiloartrites. Os temas selecionados pelos especialistas participantes, sobre os quais foram estabelecidas considerações quanto à segurança do uso de drogas biológicas, foram: ocorrência de infecções (bacterianas, virais, tuberculose), reações infusionais, reações hematológicas, neurológicas, gastrointestinais, cardiovasculares, ocorrências neoplásicas (neoplasias sólidas e da linhagem hematológica), imunogenicidade, outras ocorrências e reposta vacinal. Optou-se, por motivos didáticos, por se fazer um resumo da avaliação de segurança, de acordo com os tópicos anteriores, por classe de drogas/mecanismo de ação (antagonistas do fator de necrose tumoral, bloqueador da co-estimulação do linfócito T, depletor de linfócito B e bloqueador do receptor de interleucina-6). Em separado, foram tecidas considerações gerais sobre segurança do uso de biológicos na gravidez e na lactação. Esta revisão procura oferecer uma atualização ampla e equilibrada das experiências clínica e experimental acumuladas nas últimas duas décadas de uso de medicamentos imunobiológicos para o tratamento da AR e espondiloartrites.

The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment.