Interaction of TNFi and conventional synthetic DMARD in SARS-CoV-2 vaccine response in axial spondyloarthritis and psoriatic arthritis.

OBJECTIVES: To evaluate humoral responses to three doses of the inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with spondyloarthritis (SpA) and the effect of therapy, compared with a control group (CG). METHODS: Prospective cohort of axial SpA/psoriatic arthritis patients and age/sex-balanced CG from the CoronavRheum phase 4 trial (NCT04754698). CoronaVac was given in two doses (28-days interval) with a booster at day 210. Blood samples were collected in the days 0/28 (D28)/69 (D69) and 240 (D240) to evaluate anti-SARS-CoV-2 IgG seropositivity (SP) and neutralising antibodies (NAb). RESULTS: One hundred and ninety-four SpA patients were enrolled and 183 patients were age/sex-balanced with 183 CG. At D69, SpA patients showed a high SP (80.2% vs. 95.7%, P<0.001) and moderate NAb positivity (61.6% vs. 82.7%, P<0.001), but lower than CG. In patients, older age prednisone (P<0.001), methotrexate (MTX) (P<0.001) and TNF inhibitors (TNFi) (P<0.001) were independently associated with lower SP, while Caucasian ethnicity (P<0.05) and prednisone (P<0.01) were associated with diminished NAb. In contrast, sulfasalazine (SSZ) use was associated with NAb presence (P<0.05). In monotherapy, only TNFi was also associated with absence of SP (P<0.05). Further comparison with CG revealed that TNFi and/or MTX negatively impacted SP/NAb (P<0.05). In contrast, patients under SSZ monotherapy achieved 100% SP (P>0.999) and 83.3% NAb positivity (P>0.999). SSZ+TNFi combination resulted in a similar response than CG [SP (P=0.153) and NAb (P=0.715)]. After third dose (D69-D240), a major increment occurred for SP (81.3% to 93.1%, P<0.001) and NAb (63.2% to 86.1%, P<0.001), but still lower than CG (P<0.05), and only TNFi impaired both SP (P=0.016)/NAb (P=0.002). CONCLUSIONS: We provided novel data demonstrating that TNFi attenuates immunogenicity in SpA patients while SSZ has a positive impact on vaccine antibody production. We also confirmed that MTX in combination with TNFi had a major negative impact in vaccine humoral response (CoronavRheum clinicaltrials.gov #NCT04754698).

Anti-alpha-enolase antibodies in Behçet's disease: a marker of mucocutaneous and articular disease activity?

OBJECTIVES: To assess IgM anti-alpha-enolase antibodies (AAEA) in systemic Behçet's disease (BD) and its possible association with clinical manifestations and disease activity. METHODS: Ninety-seven consecutively selected BD patients were compared to 36 enteropathic spondyloarthritis (ESpA) [24 Crohn's disease (CD) and 12 ulcerative colitis (UC)] patients and 87 healthy controls. IgM AAEA was detected by immunoblotting. Disease activity was assessed by standardised indexes, Brazilian BD Current Activity Form (BR-BDCAF) for BD and Harvey-Bradshaw Index (HBI) for CD and UC patients. A second evaluation was performed in BD patients (n=56), regarding IgM AAEA presence, disease activity scores and C-reactive protein (CRP). RESULTS: Higher IgM AAEA prevalence was found in 97 BD (17.7%) compared to ESpA (2.8%) and healthy controls (2.3%), p<0.001. IgM AAEA frequency was higher in active BD compared to inactive BD (30.2% vs. 7.4%, p=0.006), a finding confirmed in the second cross-sectional evaluation of 56 of these BD patients (45.5% vs. 13.3%, p=0.02). Mean BR-BDCAF scores were higher in IgM AAEA positive group on both evaluations (9.1 ± 5.4 vs. 4.9 ± 4.9, p=0.002; 5.0 ± 4.9 vs. 2.2 ± 2.9, p=0.01, respectively). BD patients with mucocutaneous and articular symptoms presented higher IgM AAEA positivity in the first and second evaluations (64.7% vs. 27.5%, p=0.005; 36.4% vs. 7.1%, p=0.039 respectively). CONCLUSIONS: Our data support the notion that alpha-enolase is a target antigen in BD, particularly associated with disease activity, mucocutaneous and articular involvement. In addition, IgM AAEA may distinguish BD from ESpA, especially in patients with high disease activity.

Factors associated with ASDAS remission in a long-term study of ankylosing spondylitis patients under tumor necrosis factor inhibitors.

OBJECTIVE: To determine the clinical and demographic factors associated with disease remission and drug survival in patients with ankylosing spondylitis (AS) on TNF inhibitors. METHODS: Data from a longitudinal electronic database of AS patients under anti-TNF therapy between June/2004 and August/2013. Demographic, clinical parameters, disease activity by ASDAS remission (< 1.3) and inactive/low (< 2.1) were analyzed to characterize reasons for drug survival and switching of anti-TNF. RESULTS: Among 117 AS patients, 69 (59%) were prescribed only one anti-TNF, 48 (41%) switched to a second anti-TNF and 13 (11%) to a third anti-TNF. Considering ASDAS-CRP < 1.3, 31 (39%) patients were inactive at the end of the study. Non-switchers (P = 0.04), younger age (P = 0.004), non-smoking (P = 0.016), shorter disease duration (P = 0.047), more frequent use of SSZ (P = 0.037) and lower BASDAI (P = 0.027), BASMI (P = 0.034) and BASFI (P = 0.003) at baseline were associated with remission. In the multivariate analysis younger age (P = 0.016) and lower BASDAI (P = 0.032) remained as remission predictors. CONCLUSION: This study supports that ASDAS-CRP remission is an achievable goal not only for non-switchers but also for second anti-TNF, particularly in patients with younger age and lower BASDAI at baseline. Co-medication and non-smoker status seems to have a beneficial effect in anti-TNF response in this population.

Quality of life in spondyloarthritis: analysis of a large Brazilian cohort.

OBJECTIVE: To analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). METHODS: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. RESULTS: The mean ASQoL score was 7.74 (+5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p=0.014) and African-Brazilian ethnicity (p<0.001). The analysis of the clinical symptoms showed that buttock pain (p=0.032), cervical pain (p<0.001) and hip pain (p=0.001) were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p<0.001) and biologic agents (p=0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores. CONCLUSION: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life.

IL-23/Th17 axis is not influenced by TNF-blocking agents in ankylosing spondylitis patients.

BACKGROUND: Advances in pathophysiology and treatment of ankylosing spondylitis (AS) was recently demonstrated. However, the effect of anti-TNF in the newly described inflammatory pathways involved pathogenesis of this disease remains to be determined. The aim of our study was, therefore, to investigate long-term influence of anti-TNF drugs in IL-23/IL-17 axis of AS patients and their possible correlation with treatment, clinical, laboratory and radiographic parameters. METHODS: Eighty-six AS anti-TNF naïve patients, 47 referred for anti-TNF therapy (active-AS; BASDAI ≥ 4) and 39 with BASDAI < 4 (control-AS) were included. The active group was evaluated at baseline, 12-months and 24-months after TNF blockade and compared at baseline to control-AS group and to 47 healthy age- and gender-matched controls. Plasma levels of IL-17A, IL-22, IL-23 and PGE2 were measured. Non-steroidal anti-inflammatory drugs (NSAIDs) intake were recorded every 6 months. Radiographic severity and progression was assessed by mSASSS at baseline and 24 months after therapy. RESULTS: At baseline, active-AS group presented higher IL-23 and PGE2 levels compared to control-AS group (p < 0.001 and p = 0.008) and to healthy controls (p < 0.001 and p = 0.02). After 24-months of TNF blockade, IL-23 and PGE2 remained elevated with higher levels compared with the healthy group (p < 0.001 and p = 0.03) in spite of significant improvements in all clinical/inflammatory parameters (p < 0.001). Further analysis of 27 anti-TNF-treated patients who achieved a good response (ASDAS-CRP < 2.1,with a drop ≥ 1.1) at 24-months revealed that IL-23 plasma levels remained higher than healthy controls (p < 0.001) and higher than control-AS group with similar disease activity (ASDAS-CRP < 2.1, p = 0.01). In active-AS group (n = 47), there was a strong correlation between IL-23 and IL-17A at baseline, 12-months and 24-months after anti-TNF therapy (p ≤ 0.001). CONCLUSION: This study provides novel data demonstrating that the IL-23/IL-17 axis is not influenced by TNF blockade in AS patients despite clinical and inflammation improvements and NSAID intake.

Qualidade de vida nas espondiloartrites: análise de uma grande coorte brasileira / Quality of life in spondyloarthritis: analysis of a large Brazilian cohort

Resumo Objetivo: Analisar as variáveis demográficas e clínicas associadas à diminuição da qualidade de vida em uma grande coorte brasileira de pacientes com espondiloartrite (EpA). Métodos: Foi aplicado um protocolo de pesquisa único a 1.465 pacientes brasileiros classificados como tendo EpA de acordo com os critérios do European Spondyloarthropaties Study Group (ESSG), atendidos em 29 centros de referência em reumatologia do Brasil. Foram registradas as variáveis clínicas e demográficas. A qualidade de vida foi analisada por meio do questionário Ankylosing Spondylitis Quality of Life (ASQoL). Resultados: A pontuação média do ASQoL foi de 7,74 (+ 5,39). Ao analisar doenças específicas no grupo de EpA, as pontuações do ASQoL não apresentaram diferença estatisticamente significativa. Os dados demográficos mostraram piores escores de ASQoL associados ao gênero feminino (p = 0,014) e etnia negra (p < 0,001). Quanto aos sintomas clínicos, a dor na região glútea (p = 0,032), a dor cervical (p < 0,001) e a dor no quadril (p = 0,001), estiveram estatisticamente associadas a piores escores no ASQoL. O uso contínuo de fármacos anti-inflamatórios não esteroides (p < 0,001) e agentes biológicos (p = 0,044) esteve associado a escores mais elevados de ASQoL, enquanto outros medicamentos não interferiram nos escores do ASQoL. Conclusão: Nesta grande série de pacientes com EpA, o sexo feminino e a etnia negra, bem como sintomas predominantemente axiais, estiveram associados a uma qualidade de vida reduzida.

Abstract Objective: To analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (± 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African-Brazilian ethnicity (p < 0.001). Regarding clinical symptoms, buttock pain (p = 0.032), cervical pain (p < 0.001) and hip pain (p = 0.001), were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biologic agents (p = 0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores. Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life.

Avaliação do desempenho do BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) numa coorte brasileira de 1492 pacientes com espondiloartrites: dados do Registro Brasileiro de Espondiloartrites (RBE) / Evaluation of performance of BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) in a Brazilian cohort of 1492 patients with spondyloarthritis: data from the Brazilian Registry of Spondyloarthritides (RBE)

Objetivo Avaliar os resultados da aplicação do Índice de Atividade de Doença da Espondilite Anquilosante de Bath (BASDAI) numa série de pacientes brasileiros com EpA e estabelecer suas correlações com as variáveis específicas do grupo. Métodos Um protocolo comum de investigação foi prospectivamente aplicado em 1.492 pacientes brasileiros classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartropatias (ESSG), acompanhados em 29 centros de referência em reumatologia no Brasil. Variáveis clínicas, demográficas e índices de doença foram colhidos. Os valores totais do BASDAI foram comparados com a presença das diferentes variáveis. Resultados O valor médio do BASDAI foi de 4,20 ± 2,38. Os escores médios do BASDAI foram mais elevados nos pacientes com forma clínica combinada, comparado às formas axiais e periféricas isoladas, nos pacientes do sexo feminino e nos sedentários. Com relação ao componente axial, valores mais altos do BASDAI estiveram significativamente associados à lombalgia inflamatória, à dor alternante em nádegas, à dor cervical e ao acometimento de coxofemorais. Houve associação estatística entre os valores do BASDAI e o comprometimento periférico, relacionado ao número de articulações inflamadas, tanto dos membros inferiores quanto dos membros superiores, e às entesites. A positividade do HLA-B27 e a presença de manifestações extra-articulares não estiveram correlacionadas com os valores médios do BASDAI. Valores mais baixos do BASDAI estiveram associados ao uso de agentes biológicos (p < 0,001). Conclusão Nesta série heterogênea de pacientes brasileiros com EpA, o BASDAI conseguiu demonstrar “atividade de doença” tanto nos pacientes com acometimento axial quanto naqueles com envolvimento periférico. .

Objective To analyze the results of the application of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in a large series of Brazilian patients with the diagnosis of SpA and establish its correlations with specific variables into the group. Methods A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyoarthropathies Study Group (ESSG), attended at 29 referral centers of Rheumatology in Brazil. Clinical and demographic variables, and disease indices (BASDAI, Basfi, Basri, Mases, ASQol) were applied. The total values of BASDAI were compared to the presence of the different variables. Results The mean score of BASDAI was 4.20 ± 2.38. The mean scores of BASDAI were higher in patients with the combined (axial + peripheral + entheseal) (4.54 ± 2.38) clinical presentation, compared to the pure axial (3.78 ± 2.27) or pure peripheral (4.00 ± 2.38) clinical presentations (P < 0.001). BASDAI also presented higher scores associated with the female gender (P < 0.001) and patients who did not practice exercises (P < 0.001). Regarding the axial component, higher values of BASDAI were significantly associated with inflammatory low back pain (P < 0.049), alternating buttock pain (P < 0.001), cervical pain (P < 0.001) and hip involvement (P < 0.001). There was also statistical association between BASDAI scores and the peripheral involvement, related to the lower (P = 0.004) and upper limbs (P = 0.025). The presence of enthesitis was also associated to higher scores of BASDAI (P = 0.040). Positive HLA-B27 and the presence of cutaneous psoriasis, inflammatory bowel disease, uveitis and urethritis were not correlated with the mean scores of BASDAI. Lower scores of BASDAI were associated with the use of biologic agents (P < 0.001). Conclusion In this heterogeneous Brazilian series of SpA patients, BASDAI was able to demonstrate “disease ...

Diminished ovarian reserve in Behçet's disease patients.

This study aims to assess ovarian reserve markers in Behçet's disease (BD) patients. Ten BD and 22 healthy controls were evaluated for ovarian reserve by examining the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, inhibin B, total morning testosterone, prolactin, thyroid-stimulating hormone (TSH), and antral follicle count. Anti-Müllerian hormone (AMH) was measured using two different enzyme-linked immunosorbent assay (ELISA) kits. Demographic data, menstrual abnormalities, disease parameters, and treatments were also analyzed. The median current age was similar in BD patients and controls (34 (20-40) vs. 31.3 (20-42) years, p = 0.33). A positive correlation was observed between the AMH Gen II ELISA and AMH/MISAnshLabs ELISA assays in the BD patients (r = +0.98; p < 0.0001) and healthy controls (r = +0.93; p < 0.0001). The mean AMH by Gen II (0.93 ± 0.8 vs. 2.59 ± 1.8 ng/mL, p = 0.01) and AMH/MIS AnshLabs ELISA (1.07 ± 0.86 vs. 2.51 ± 1.8 ng/mL, p = 0.02) were significantly reduced in the BD patients versus controls. A trend of decreased AMH (<1.0 ng/mL) was observed in BD patients compared to that in the controls (50 vs. 19 %, p = 0.09) using either kits. The mean FSH was significantly higher in the BD patients compared to that in the controls (9.1 ± 3.6 vs. 6.5 ± 2.7, p = 0.04). No differences were found for the other ovarian parameters in both groups (p > 0.05). Current disease activity was only observed in BD patients with a low AMH level; however, there was no statistical significance (40 vs. 0 %, p = 0.44). Cyclophosphamide use was reported in only one patient with a low AMH and high FSH level. The present study was the first to suggest that BD patients may have diminished ovarian reserve. The contribution of disease activity remains to be determined.

[Evaluation of performance of BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) in a Brazilian cohort of 1,492 patients with spondyloarthritis: data from the Brazilian Registry of Spondyloarthritides (RBE)]. / Avaliação do desempenho do BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) numa coorte brasileira de 1.492 pacientes com espondiloartrites: dados do Registro Brasileiro de Espondiloartrites (RBE).

OBJECTIVE: To analyze the results of the application of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in a large series of Brazilian patients with the diagnosis of SpA and establish its correlations with specific variables into the group. METHODS: A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyoarthropathies Study Group (ESSG), attended at 29 referral centers of Rheumatology in Brazil. Clinical and demographic variables, and disease indices (BASDAI, Basfi, Basri, Mases, ASQol) were applicated. The total values of BASDAI were compared to the presence of the different variables. RESULTS: The mean score of BASDAI was 4.20 ± 2.38. The mean scores of BASDAI were higher in patients with the combined (axial + peripheral + entheseal) (4.54 ± 2.38) clinical presentation, compared to the pure axial (3.78 ± 2.27) or pure peripheral (4.00 ± 2.38) clinical presentations (p<0.001). BASDAI also presented higher scores associated with the female gender (p<0.001) and patients who did not practice exercises (p < 0.001). Regarding the axial component, higher values of BASDAI were significantly associated with inflammatory low back pain (p<0.049), alternating buttock pain (p<0.001), cervical pain (p<0.001) and hip involvement (p<0.001). There was also statistical association between BASDAI scores and the peripheral involvement, related to the lower (p=0.004) and upper limbs (p=0.025). The presence of enthesitis was also associated to higher scores of BASDAI (p=0.040). Positive HLA-B27 and the presence of cutaneous psoriasis, inflammatory bowel disease, uveitis and urethritis were not correlated with the mean scores of BASDAI. Lower scores of BASDAI were associated with the use of biologic agents (p<0.001). CONCLUSION: In this heterogeneous Brazilian series of SpA patients, BASDAI was able to demonstrate "disease activity" in patients with axial as well as peripheral disease.

[Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort]. / Perfil epidemiológico da espondiloartrite de início juvenil comparada com a espondiloartrite de início na vida adulta em uma grande coorte brasileira.

OBJECTIVE: To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. PATIENTS AND METHODS: Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE - Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). RESULTS: Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index - BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA. CONCLUSIONS: Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores.

Perfil epidemiológico da espondiloartrite de início juvenil comparada com a espondiloartrite de início na vida adulta em uma grande coorte brasileira / Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort

Objetivo Analisar as características clínicas e epidemiológicas das espondiloartrites (EpA) de início juvenil (< 16 anos) e compará-las com um grupo de pacientes com EspA de início na vida adulta (≥ 16 anos). Pacientes e métodos Coorte prospectiva, observacional e multicêntrica com 1.424 pacientes com diagnóstico de EspA de acordo com o European Spondyloarthropathy Study Group (ESSG) submetidos a um protocolo comum de investigação e recrutados em 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE). Os pacientes foram divididos em dois grupos: idade no início<16 anos (grupo EspAiJ) e idade no início ≥ 16 anos. Resultados Entre os 1.424 pacientes, 235 manifestaram o início da doença antes dos 16 anos (16,5%). As variáveis clínicas e epidemiológicas associadas com a EspAiJ foram: gênero masculino (p<0,001), artrite em membro inferior (p=0,001), entesite (p=0,008), uveíte anterior (p=0,041) e HLA-B27 positivo (p=0,017), em associação com escores mais baixos de atividade da doença (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI; p=0,007) e de capacidade funcional (Bath Ankylosing Spondylitis Functional Index – BASFI; p=0,036). A psoríase cutânea (p<0,001), a doença inflamatória intestinal (p=0,023), a dactilite (p=0,024) e o envolvimento ungueal (p=0,004) foram mais frequentes em pacientes com EspA de início na vida adulta. Conclusões Nessa grande coorte brasileira, os pacientes com EspAiJ se caracterizavam predominantemente pelo gênero masculino, envolvimento periférico (artrite e entesite), HLA-B27 positivo e escores de doença mais baixos. .

Objective To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. Patients and methods Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE – Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). Results Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index – BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA. Conclusions Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores. .

Assessment of fatigue in a large series of 1492 Brazilian patients with Spondyloarthritis.

BACKGROUND: The aim of the present study was to analyze the score of fatigue in a large cohort of Brazilian patients with SpA, comparing different disease patterns and its association with demographic and disease-specific variables. METHODS: A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyloarthropathies Study Group (ESSG) criteria, attended at 29 reference centers. Clinical and demographic variables were recorded. Fatigue was evaluated using the first item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. RESULTS: The mean BASDAI fatigue score was 4.20 ± 2.99. There was no significant difference in the fatigue score between the different SpA. Fatigue was higher in female patients (p < 0.001), with mixed (axial + peripheral) involvement (p < 0.001) and in those who did not practice exercises (p < 0.001). Higher scores of fatigue were significantly associated with inflammatory low back pain (p = 0.013), alternating buttock pain (p = 0.001), cervical pain (p = 0.001), and hip involvement (p = 0.005). Fatigue presented a moderate positive statistical correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) (0.469; p < 0.001) and Ankylosing Spondylitis Quality of Life (0.462; p < 0.001). CONCLUSION: In this large series of Brazilian SpA patients, higher fatigue scores were associated with female gender, sedentary, worse functionality, and quality of life.

Profile of the use of disease modifying drugs in the Brazilian Registry of Spondyloarthritides.

INTRODUCTION: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). METHODS: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). RESULTS: At least one DMD was used by 73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). CONCLUSION: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Perfil do uso de drogas modificadoras de doenca no Registro Brasileiro de Espondiloartrites / Profile of the use of disease modifying drugs in the Brazilian Registry of Spondyloarthritides

Introdução: Poucos estudos avaliaram o perfil do uso de drogas modificadoras de doença (DMD) em pacientes brasileiros com diagnóstico de espondiloartrite (EpA). Métodos: Um protocolo comum de investigação foi prospectivamente aplicado em 1505 pacientes classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartrites (ESSG), acompanhados em 29 centros de referência em Reumatologia no Brasil. Variáveis clínicas e demográficas foram obtidas e avaliadas, analisando-se suas correlações com o uso das DMD metotrexato (MTX) e sulfasalazina (SSZ). Resultados: Pelo menos uma DMD foi utilizada por 73,6% dos pacientes, sendo MTX por 29,2% e SSZ por 21,7%, enquanto 22,7% utilizaram ambas as drogas. O uso do MTX foi significativamente associado ao acometimento periférico, e a SSZ foi associada ao comprometimento axial, sendo que as duas drogas foram mais utilizadas, isoladas ou combinadas, no comprometimento misto (p < 0,001). O uso de uma DMD esteve significativamente associado à etnia branca (MTX; p = 0,014), lombalgia inflamatória (SSZ; p = 0,002), dor em nádegas (SSZ; p = 0,030), cervicalgia (MTX; p = 0,042), artrite de membros inferiores (MTX; p < 0,001), artrite de membros superiores (MTX; p < 0,001), entesite (p = 0,007), dactilite (MTX; p < 0,001), doença inflamatória intestinal (SSZ; p < 0,001) e acometimento ungueal (MTX; p < 0,001). Conclusão: O uso de pelo menos uma DMD foi referido por mais de 70% dos pacientes numa grande coorte brasileira de pacientes com EpA, sendo o uso do MTX mais associado ao acometimento periférico e o uso da SSZ mais associado ao acometimento axial. .

Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). Results: At least one DMD was used by 73.6 % of patients: MTX by 29.2 % and SSZ by 21.7%, while 22.7 % used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement. .

Artrite enteropática no Brasil: dados do registro brasileiro de espondiloartrites / Enteropathic arthritis in Brazil: data from the brazilian registry of spondyloarthritis

As doenças inflamatórias intestinais (doença de Crohn e retocolite ulcerativa) apresentam manifestações extraintestinais em um quarto dos pacientes, sendo a mais comum a artrite enteropática. MÉTODOS: Estudo prospectivo, observacional e multicêntrico, realizado com pacientes de 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE), que se incorpora ao grupo RESPONDIA (Registro Ibero-americano de Espondiloartrites). Dados demográficos e clínicos de 1472 pacientes foram colhidos, e aplicaram-se questionários padronizados de avaliação de mobilidade axial, de qualidade de vida, de envolvimento entesítico, de atividade de doença e de capacidade funcional. Exames laboratoriais e radiográficos foram realizados. Objetivamos, neste presente artigo, comparar as características clínicas, epidemiológicas, genéticas, imagenológicas, de tratamento e prognóstico de enteroartríticos com os outros espondiloartríticos nesta grande coorte brasileira. RESULTADOS: Foram classificados como enteroartrite 3,2% dos pacientes, sendo que 2,5% tinham espondilite e 0,7%, artrite (predomínio periférico). O subgrupo de indivíduos com enteroartrite apresentava maior prevalência de mulheres (P < 0,001), menor incidência de dor axial inflamatória (P < 0,001) e de entesite (P = 0,004). O HLA-B27 foi menos frequente no grupo de enteroartríticos (P = 0,001), mesmo se considerado apenas aqueles com a forma axial pura. Houve menor prevalência de sacroiliíte radiológica (P = 0,009) e também menor escore radiográfico (BASRI) (P = 0,006) quando comparado aos pacientes com as demais espondiloartrites. Também fizeram mais uso de corticosteroides (P < 0,001) e sulfassalasina (P < 0,001) e menor uso de anti-inflamatórios não hormonais (P < 0,001) e metotrexato (P = 0,001). CONCLUSÃO: Foram encontradas diferenças entre as enteroartrites e as demais espondiloartrites, principalmente maior prevalência do sexo feminino, menor frequência do HLA-B27, associados a uma menor gravidade do acometimento axial.

Inflammatory bowel diseases (Crohn's disease and ulcerative rectocolitis) have extraintestinal manifestations 25% of the patients, with the most common one being the enteropathic arthritis. METHODS: Prospective, observational, multicenter study with patients from 29 reference centers participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the assessment of axial mobility, quality of life, enthesitic involvement, disease activity and functional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treatment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort. RESULTS: A total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spondylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with enteroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less non-steroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001). CONCLUSION: There were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.

An analysis of 372 patients with anterior uveitis in a large Ibero-American cohort of spondyloarthritis: the RESPONDIA Group.

OBJECTIVES: This study analysed the frequency of anterior uveitis (AU) and its correlations in a large cohort of patients with spondyloarthritis (SpA). METHODS: A common protocol of investigation was prospectively applied to 2012 SpA patients in 85 centres from 10 Ibero-American countries. Clinical and demographic variables and disease indexes were investigated. Categorical variables were compared by χ2 and Fisher's exact test, and continuous variables were compared by ANOVA or Kruskal-Wallis test. A value of p<0.05 was considered significant. RESULTS: AU was referred by 372 SpA patients (18.5%). AU was statistically associated with inflammatory low back pain (p<0.001), radiographic sacroiliitis (p<0.001), enthesopathies (p=0.004), urethritis/acute diarrhoea (p<0.001), balanitis (p=0.002), hip involvement (p=0.002), HLA-B27 (p=0.003), and higher C-reactive protein (p=0.001), whilst it was negatively associated with the number of painful (p=0.03) and swollen (p=0.005) peripheral joints, psoriatic arthritis (p<0.001), psoriasis (p<0.001), nail involvement (p<0.001), and dactilitis (p=0.062; trend). No association with gender, race, and indices (disease activity, functionality and quality of life) was observed. Logistic regression showed that ankylosing spondylitis (p=0.001) and HLA-B27 (p=0.083; trend) was significantly associated with AU, while extra-articular manifestations (predominantly psoriasis) were negatively associated (p=0.016). CONCLUSIONS: Anterior uveitis is a frequent extra-articular manifestation in SpA patients, positively associated with axial involvement and HLA-B27 and negatively associated with peripheral involvement and psoriatic arthritis.

Enteropathic arthritis in Brazil: data from the Brazilian Registry of Spondyloarthritis.

UNLABELLED: Inflammatory bowel diseases (Crohn's disease and ulcerative rectocolitis) have extraintestinal manifestations 25% of the patients, with the most common one being the enteropathic arthritis. METHODS: Prospective, observational, multicenter study with patients from 29 reference centers participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the assessment of axial mobility, quality of life, enthesitic involvement, disease activity and functional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treatment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort. RESULTS: A total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spondylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with enteroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less non-steroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001). CONCLUSION: There were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

OBJECTIVE: To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. METHODS: A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. RESULTS: The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09). CONCLUSION: Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.

Gender characterization in a large series of Brazilian patients with spondyloarthritis.

An increasing number of women have been diagnosed with spondyloarthritis (SpA) in recent decades. While a few studies have analyzed gender as a prognostic factor of the disease, no studies have addressed this matter with a large number of patients in South America, which is a peculiar region due to its genetic heterogeneity. The aim of the present study was to analyze the influence of gender on disease patterns in a large cohort of Brazilian patients with SpA. A prospective study was carried out involving 1,505 patients [1,090 males (72.4%) and 415 females (27.6%)] classified as SpA according to the European Spondyloarthropaties Study Group criteria who attended at 29 reference centers for rheumatology in Brazil. Clinical and demographic variables were recorded and the following disease indices were administered: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiologic Index (BASRI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and Ankylosing Spondylitis Quality of Life (ASQoL). Ankylosing spondylitis (AS) was the most frequent disease in the group (65.4%), followed by psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), arthritis associated to inflammatory bowel disease (3.2%), and juvenile SpA (2.9%). The male-to-female ratio was 2.6:1 for the whole group and 3.6:1 for AS. The females were older (p < 0.001) and reported shorter disease duration (p = 0.002) than the male patients. The female gender was positively associated to peripheral SpA (p < 0.001), upper limb arthritis (p < 0.001), dactylitis (p = 0.011), psoriasis (p < 0.001), nail involvement (p < 0.001), and family history of SpA (p = 0.045) and negatively associated to pure axial involvement (p < 0.001), lumbar inflammatory pain (p = 0.042), radiographic sacroiliitis (p < 0.001), and positive HLA-B27 (p = 0.001). The number of painful (p < 0.001) and swollen (p = 0.006) joints was significantly higher in the female gender, who also achieved higher BASDAI (p < 0.001), BASFI (p = 0.073, trend), MASES (p = 0.019), ASQoL (p = 0.014), and patient's global assessment (p = 0.003) scores, whereas the use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biological agents (p = 0.003) was less frequent in the female gender. Moreover, BASRI values were significantly lower in females (p < 0.001). The female gender comprised one third of SpA patients in this large cohort and exhibited more significant peripheral involvement and less functional disability, despite higher values in disease indices.

Ethnic influence in clinical and functional measures of Brazilian patients with spondyloarthritis.

OBJECTIVE: Spondyloarthritides (SpA) can present different disease spectra according to ethnic background. The Brazilian Registry of Spondyloarthritis (RBE) is a nationwide registry that comprises a large databank on clinical, functional, and treatment data on Brazilian patients with SpA. The aim of our study was to analyze the influence of ethnic background in SpA disease patterns in a large series of Brazilian patients. METHODS: A common protocol of investigation was prospectively applied to 1318 SpA patients in 29 centers distributed through the main geographical regions in Brazil. The group comprised whites (65%), African Brazilians (31.3%), and people of mixed origins (3.7%). Clinical and demographic variables and various disease index scores were compiled. Ankylosing spondylitis (AS) was the most frequent disease in the group (65.1%); others were psoriatic arthritis (18.3%), undifferentiated SpA (6.8%), enteropathic arthritis (3.7%), and reactive arthritis (3.4%). RESULTS: White patients were significantly associated with psoriasis (p = 0.002), positive HLA-B27 (p = 0.014), and use of corticosteroids (p < 0.0001). Hip involvement (p = 0.02), axial inflammatory pain (p = 0.04), and radiographic sacroiliitis (p = 0.025) were associated with African Brazilian descent. Sex distribution, family history, and presence of peripheral arthritis, uveitis, dactylitis, urethritis, and inflammatory bowel disease were similar in the 3 groups, as well as age at disease onset, time from first symptom until diagnosis, and use of anti-tumor necrosis factor-α agents (p > 0.05). Schober test and thoracic expansion were similar in the 3 groups, whereas African Brazilians had higher Maastricht Ankylosing Spondylitis Enthesitis Scores (p = 0.005) and decreased lateral lumbar flexion (p = 0.003), while whites had a higher occiput-to-wall distance (p = 0.02). African Brazilians reported a worse patient global assessment of disease (p = 0.011). Other index scores and prevalence of work incapacity were similar in the 3 groups, although African Brazilians had worse performance in the Ankylosing Spondylitis Quality of Life questionnaire (p < 0.001). CONCLUSION: Ethnic background is associated with distinct clinical aspects of SpA in Brazilian patients. African Brazilian patients with SpA have a poorer quality of life and report worse disease compared to whites.