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OBJECTIVE: To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. METHODS: Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. RESULTS: The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. CONCLUSION: SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.
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Anticorpos Monoclonais Humanizados , Antirreumáticos , Artrite Reumatoide , Infecções Irruptivas , COVID-19 , Espondilartrite , Humanos , Antirreumáticos/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Vacinas de mRNA , Vacina BNT162 , Fator de Necrose Tumoral alfa , Resultado do Tratamento , Metotrexato/uso terapêutico , Espondilartrite/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológicoRESUMO
Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin' s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S.
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Artrite Reumatoide , Basigina , Catepsinas , Endostatinas , Piperidinas , Pirimidinas , Humanos , Basigina/metabolismo , Basigina/genética , Piperidinas/farmacologia , Endostatinas/metabolismo , Endostatinas/farmacologia , Pirimidinas/farmacologia , Catepsinas/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Fator de Transcrição STAT3/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Feminino , Pessoa de Meia-Idade , Masculino , Pirróis/farmacologia , Linhagem CelularRESUMO
OBJECTIVES: To evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls. METHODS: A prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2-6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample. RESULTS: The two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2-6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1. CONCLUSIONS: The two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.
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Doenças Autoimunes , Vacina BNT162 , COVID-19 , Imunogenicidade da Vacina , Doenças Reumáticas , Abatacepte/uso terapêutico , Adulto , Anticorpos Antivirais , Antirreumáticos/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Vacina BNT162/imunologia , COVID-19/prevenção & controle , Humanos , Imunoglobulina G/uso terapêutico , Janus Quinases , Metotrexato/uso terapêutico , Estudos Prospectivos , Doenças Reumáticas/tratamento farmacológico , Rituximab/uso terapêuticoRESUMO
INTRODUCTION: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited. METHODS: A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2-6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose. RESULTS: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients. CONCLUSION: mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.
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Doenças Autoimunes/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Hospedeiro Imunocomprometido/imunologia , Imunogenicidade da Vacina/imunologia , Doenças Reumáticas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Doenças Autoimunes/tratamento farmacológico , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2 , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to compare patients with ankylosing spondylitis with psoriasis (ASP) and without psoriasis (AS), to axial PsA (axPsA) patients. METHODS: Two adult cohorts were recruited from the AS clinic: ASP and AS. These two cohorts were compared with two adult cohorts recruited from the PsA clinic: axPsA (radiographic sacroiliitis: ⩾bilateral grade 2 or unilateral grade 3 or 4); and Peripheral PsA. All patients were followed prospectively according to the same protocol. The demographic, clinical and radiographic variables were compared. Adjusted means were used to account for varying intervals between visits. A logistic regression was performed and adjusted for follow-up duration. RESULTS: There were 477 axPsA patients, 826 peripheral PsA, 675 AS and 91 ASP patients included. AS patients were younger (P < 0.001), more male and HLA-B*27 positive (76%, 72% vs 64%, P ⩽ 0.001, 82%, 75%, vs 19%, P = 0.001). They had more back pain at presentation (90%, 92% vs 19%, P = 0.001), worse axial disease activity scores (bath ankylosing spondylitis disease activity index: 4.1, 3.9 vs 3.5 P = 0.017), worse back metrology (bath ankylosing spondylitis metrology index: 2.9, 2.2 vs 1.8, P < 0.001), worse physician global assessments (2.4, 2.2 vs 2.1, P < 0.001), were treated more with biologics (29%, 21% vs 7%, P = 0.001) and had a higher grade of sacroiliitis (90%, 84% vs 51%, P < 0.001). Similar differences were detected in the comparison of ASP to axPsA and in a regression model. CONCLUSION: AS patients, with or without psoriasis, seem to be different demographically, genetically, clinically and radiographically from axPsA patients. axPsA seems to be a distinct entity.
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Artrite Psoriásica/diagnóstico por imagem , Psoríase/complicações , Espondilite Anquilosante/diagnóstico por imagem , Adulto , Artrite Psoriásica/complicações , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Adulto JovemRESUMO
BACKGROUND: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. MATERIALS AND METHODS: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. RESULTS: Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01). CONCLUSIONS: This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Ansiedade/psicologia , Artrite Reumatoide/tratamento farmacológico , Depressão/psicologia , Adulto , Fatores Etários , Idoso , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/psicologia , Peso Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA. OBJECTIVES: To evaluate SC tocilizumab in a real-life clinical setting. METHODS: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed. RESULTS: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively. CONCLUSIONS: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo PacienteRESUMO
Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. Dyslipidemia is a known adverse effect of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody used in RA treatment. We aimed to assess the effect of TCZ on lipid profile and adipokine levels in RA patients. Height, weight, disease activity scores, lipid profile and atherogenic indices (AI), leptin, adiponectin, resistin, interleukin-6, and high-sensitivity C-reactive protein (CRP) were measured before and four months after initiation of TCZ in 40 RA patients and 40 healthy controls. Following TCZ treatment, total cholesterol, high density lipoprotein (HDL), and triglycerides were significantly elevated, but no significant changes in weight, body mass index (BMI), low density lipoprotein (LDL), and AI were observed. Compared with controls, significantly higher adiponectin levels were measured in the RA group at baseline. Following TCZ treatment, resistin levels and the leptin-to-adiponectin ratio increased, adiponectin levels decreased, and leptin levels remained unchanged. No correlation was found between the change in adipokine serum levels and changes in the disease activity indices, nor the lipid profile. In conclusion, the changes observed suggest a protective role for TCZ on the metabolic and cardiovascular burden associated with RA, but does not provide a mechanistic explanation for this phenomenon.
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Adipocinas/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Lipídeos/sangue , Idoso , Artrite Reumatoide/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-6/antagonistas & inibidoresRESUMO
OBJECTIVE: The aims of this study were to evaluate the prevalence of metabolic syndrome (MetS) in psoriatic arthritis (PsA) patients according to the most recent definition in a Mediterranean population and to determine its association with biomarkers of inflammation and serum adipocytokine levels. METHODS: Demographic, clinical, and laboratory data were collected on 74 patients with PsA and 82 control subjects. The presence of MetS was determined according to the current "harmonization" definition. Serum adipocytokines were analyzed. Continuous variables were compared by t test and discrete variables by χ test. Multivariate regression models compared the association between the presence of MetS and the blood levels of adipocytokines. RESULTS: The prevalence of MetS was higher in PsA patients compared with the control group: 54.8% versus 36.6%, respectively (P = 0.02; odds ratio, 2.33; 95% confidence interval, 1.16-4.69). The main difference between the 2 groups was waist circumference. No association was found between MetS and parameters of articular and skin disease activity or treatment. Leptin levels and leptin/adiponectin ratio were higher in PsA patients compared with control subjects: 83.4 versus 51.7 ng/mL (P = 0.001) and 6.3 × 10 versus 4.1 × 10 (P = 0.015), respectively. There was no significant difference in the adiponectin levels between the groups. CONCLUSIONS: The prevalence of MetS was higher in PsA patients compared with non-PsA control subjects in this Mediterranean population. Clinicians caring for PsA patients ought to be aware of the increased risk of MetS in PsA patients, confirmed in different regions worldwide. The increased MetS seems to be linked to central obesity in these patients, and appropriate treatment recommendations are advised.
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Adipocinas/sangue , Artrite Psoriásica , Síndrome Metabólica , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Antirreumáticos/classificação , Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/metabolismo , Biomarcadores/sangue , Glicemia/análise , HDL-Colesterol/sangue , Correlação de Dados , Feminino , Humanos , Israel/epidemiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Circunferência da CinturaRESUMO
INTRODUCTION: Cardiovascular (CV) morbidity and mortality is elevated in rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) patients. The inflammation not only accelerates atherosclerosis, but also influences CV risk factors such as lipid profile, blood pressure and insulin resistance. RA and PSA patients are initially treated with DMARDS (disease modifying anti-rheumatic drugs). However, if remission is not achieved in RA, a variety of biologics (anti- TNF rituximab, tocilizumab, abatacept) are added to the treatment regimen. In PSA, only anti-TNF drugs are approved. AS is treated solely by NSAIDS and anti-TNF drugs. DMARDS were found to reduce the CV morbidity in RA patients, in addition to their anti-inflammatory affect. However, it has not been proven that anti-inflammatory therapy reduces the cardiovascular risk in PSA and AS patients. Anti-TNF drugs have been shown to reduce CV morbidity and mortality in RA and AS patients, however their effect on these patient's lipid profile in not yet clear. Despite the scarce evidence available, it seems that rituximab may have a positive influence on the patient's lipid profile. Even though tocilizumab adversely affects the lipid profile, this drug's overall CV effect is still being examined in clinical trials. There is not enough evidence to determine the effect of abatacept on the lipid profile. These issues are currently in the focus of many clinical trials and no doubt these issues will be clarified in the future.
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Antirreumáticos/uso terapêutico , Artrite Psoriásica/metabolismo , Artrite Reumatoide/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Espondilite Anquilosante/metabolismo , Antirreumáticos/metabolismo , Terapia Biológica/efeitos adversos , Humanos , Lipídeos , Fator de Necrose Tumoral alfaRESUMO
During progression of rheumatoid arthritis (RA), angiogenesis provides oxygen and nutrients for the cells' increased metabolic demands and number. To turn on angiogenesis, pro-angiogenic factors must outweigh anti-angiogenic factors. We have previously shown that CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) can induce the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9) in a co-culture of the human HT1080 fibrosarcoma and U937 monocytic-like cell lines. However, whether CD147 influences anti-angiogenic factors was not known. We now show that relative to single cultures, the co-culture of these cells not only enhanced pro-angiogenic factors but also decreased the anti-angiogenic factors endostatin and thrombospondin-1 (Tsp-1), generally increasing the angiogenic potential as measured by a wound assay. Using anti-CD147 antibody, CD147 small interfering RNA (siRNA), and recombinant CD147, we demonstrate that CD147 hormetically regulates the generation of endostatin but has no effect on Tsp-1. Since endostatin is cleaved from collagen XVIII (Col18A), we applied different protease inhibitors and established that MMP-9 and proteasome 20S, but not cathepsins, are responsible for endostatin generation. MMP-9 and proteasome 20S collaborate to synergistically enhance endostatin generation, and in a non-cellular system, CD147 enhanced MMP-9 activity and hormetically regulated proteasome 20S activity. Serum samples obtained from RA patients and healthy controls mostly corroborated these findings, indicating clinical relevance. Cumulatively, these findings suggest that secreted CD147 mediates a possibly allosteric effect on MMP-9 and proteasome 20S activities and can serve as a switch that turns angiogenesis on or off, depending on its ambient concentrations in the microenvironment.
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Artrite Reumatoide , Basigina , Humanos , Artrite Reumatoide/metabolismo , Basigina/genética , Endostatinas , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Complexo de Endopeptidases do Proteassoma , Trombospondina 1 , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Glucocorticosteroid-induced osteoporosis (GIO) is the most common cause of secondary osteoporosis but is underdiagnosed and undertreated. Our aim in this communication is to review the literature on the implementation of current GIO prevention practices such as calcium and vitamin D supplementation with emphasis on the rheumatologists' perspective relating to the need for development of novel GIO educational prevention measures.
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Despite the increasing recognition of cardiac involvement in systemic sarcoidosis, the diagnosis of cardiac sarcoidosis (CS) remains challenging. Our aim is to present a comprehensive, retrospective case series of CS patients, focusing on the current diagnostic guidelines and management of this life-threatening condition. In our case series, patient data were collected retrospectively, including hospital admission records and rheumatology and cardiology clinic visit notes, detailing demographic, clinical, laboratory, pathology, and imaging studies, as well as cardiac devices and prescribed medications. Cases were divided into definite and probable CS based on the 2014 Heart Rhythm Society guidelines as well as presumed CS based on imaging criteria and clinical findings. Overall, 19 CS patients were included, 17 of whom were diagnosed with probable or presumed CS based on cardiac magnetic resonance imaging (CMR) and/or cardiac positron emission tomography using 18F-Fluorodeoxyglucose (PET-FDG) without supporting endomyocardial biopsy (EMB). The majority of CS patients were male (53%), with a mean age of 52.9 ± 11.8, with CS being the initial manifestation of sarcoidosis in 63% of cases. Most patients presented with high-grade AVB (63%), followed by heart failure (42%) and ventricular tachyarrhythmia (VT) (26%). This case series highlights the significance of utilizing updated diagnostic criteria relying on CMR and PET-FDG given that cardiac involvement can be the initial manifestation of systemic sarcoidosis, requiring prompt diagnosis and treatment to prevent morbidity and mortality.
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Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed.
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Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery. Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction. Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery. Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population.
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COVID-19 , Doenças Reumáticas , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Israel/epidemiologia , SARS-CoV-2 , Teste para COVID-19 , Vacinas contra COVID-19 , Doenças Reumáticas/epidemiologia , VacinaçãoRESUMO
OBJECTIVES: To assess the efficacy and safety of the influenza virus vaccine in systemic sclerosis (SSc) patients compared to healthy controls. METHODS: Twenty-six SSc patients and 16 healthy controls were vaccinated with a trivalent influenza subunit vaccine (H1N1 A/Brisbane/59/2007(TGA 2008/81B) (H1N1), H3N2 A/Uruguay/716/2007 (A/Brisbane/10/2007-like, NIBSC8/124) (H3N2) and B B/Brisbane/60/2008 (TGA 2009/82/B) (B)). The subjects were evaluated on the day of vaccination and 6 weeks later. Disease activity was assessed by the Rodnan score, number of ulcers, number of tender and swollen joints, the presence of dyspnea, cough, dyspepsia and dysphagia, and patient (PDAI) and physician (PHDAI) disease activity evaluation by the visual activity score (VAS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. The humoral response was evaluated by haemagglutination inhibition (HI). RESULTS: At baseline, 62%, 15% and 88% of the SSc patients had protective levels against H1N1, H3N2 and B, respectively, versus 56%, 62% and 87% for controls. Six weeks later, the proportion of responders to H1N1 was significantly higher in the SSc patients (73%) compared to controls (37.5%) (p=0.0225). The proportion of responders to H3N2 and B was similar in both groups, and both had a significant increase in geometric mean titers for each antigen. A lower response to H1N1 was associated with interstitial lung disease, while patients on combination calcium channel blockers and iloprost therapy showed significantly better response to H1N1 and B antigens. Most underlying disease activity parameters remained unchanged. CONCLUSIONS: The influenza virus vaccine was safe and generated a satisfactory humoral response in SSc patients.
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Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Escleroderma Sistêmico/complicações , Adulto , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Imunidade Humoral/efeitos dos fármacos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Influenza Humana/complicações , Influenza Humana/imunologia , Influenza Humana/virologia , Israel , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Fatores de Tempo , Resultado do Tratamento , VacinaçãoRESUMO
Disease patterns and manifestations may vary among different populations and change over time. The purpose of our study was to define the demographic, clinical, roentgenologic, and laboratory findings in a recent cohort of psoriatic arthritis patients followed up in rheumatology clinics in northern Israel. We conducted a cross-sectional study of 149 psoriatic arthritis patients. Demographic, clinical, laboratory, and radiological data, with emphasis on the pattern of arthritis, treatment regimens, and co-morbidities were obtained from patient interviews and rheumatology file reviews. The mean age of our patients was 58.2, with a female preponderance (57.3%). Skin involvement preceded the arthritis or was diagnosed simultaneously in 90.1% of cases. The most common joint involvement was an RA-like arthritis (49.7% of the patients) correlating positively with age, female gender, and disease duration. Dactylitis and nail involvement were observed in 33.6 and 36.2% of the patients, respectively. Radiographic bone erosions were noted in a third of the patients, correlating with DIP and RA-like arthritis patterns. Most patients were treated with methotrexate (73.8%) and a combination therapy (41.4%). An increased incidence of hypertension, hyperlipidemia, and diabetes mellitus was noted in our cohort compared to the general Israeli population. Our survey, the first of its kind conducted in Israel, noted a relative increase in the polyarticular manifestation of PsA and a decrease in spondyloarthropathy, compared to historic series, with more aggressive disease found in women above the age of sixty. These findings are in line with recent surveys.
Assuntos
Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Diabetes Mellitus/epidemiologia , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Testes de Química Clínica , Comorbidade , Estudos Transversais , Demografia , Quimioterapia Combinada , Saúde da Família , Feminino , Humanos , Imunossupressores/uso terapêutico , Israel/epidemiologia , Articulações/patologia , Articulações/fisiopatologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To describe the prevalence of inflammatory and structural lesions using whole spine MRI in patients with psoriatic disease, and to assess their correlation with clinical features and with axial spondyloarthritis (axSpA) classification criteria. METHODS: This retrospective analysis included patients with whole spine and sacroiliac joints (SIJ) MRI, selected from 2 populations: (1) active psoriatic arthritis (PsA), irrespective of axial symptoms; (2) psoriasis with confirmed or suspected PsA and axSpA symptoms. MRI spondylitis and/or sacroiliitis (MRI-SpA) was defined according to Assessment of Spondyloarthritis International Society (ASAS) consensus and by radiologist impression. Agreement between MRI-SpA and different inflammatory back pain (IBP) definitions (Berlin/ASAS/rheumatologist criteria) and the axSpA classification criteria were calculated considering MRI as gold standard. Logistic regression determined MRI-SpA-associated factors. RESULTS: 93 patients were analysed (69.9% PsA; 30.1% psoriasis). Back pain was present in 81.7%, defined as IBP in 36.6%-57%. MRI-SpA was found in 9.7% of patients by ASAS definition and in 12.9% by radiologist impression, of which 25% had isolated spondylitis.Low agreement was found between the three IBP definitions and MRI-SpA. Rheumatologist criteria was the most sensitive (50%-55.6%) while ASAS and Berlin criteria were the most specific (61.9%-63%). axSpA criteria had poor sensitivity for MRI-SpA (22.2%-25%). Late onset of back pain or asymptomatic patients accounted for most cases with MRI-SpA not meeting axSpA or IBP criteria. Male sex was associated with MRI-SpA (OR 6.91; 95% CI 1.42 to 33.59) in multivariable regression analysis. CONCLUSION: Prevalence of MRI-defined axSpA was low and showed poor agreement with IBP and axSpA criteria.
Assuntos
Artrite Psoriásica , Sacroileíte , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/epidemiologia , Estudos de Coortes , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Sacroileíte/diagnóstico por imagem , Sacroileíte/epidemiologiaRESUMO
Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients (n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1-10) vs. 5 (1-15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046-0.96, p = 0.044 and OR 0.189, 95% CI 0.036-0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.
RESUMO
BACKGROUND: Persistence of biologic therapy in psoriatic arthritis (PsA) patients is an important factor in individualized patient treatment planning and healthcare policy and guideline development. OBJECTIVE: To estimate the persistence of biologic agents prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients. METHODS: Patients with PsA from a large healthcare provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1, 2002, until December 31, 2018, were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a permissible lag time of 6 months from the time of prescription issuance until medication filling date was exceeded. Treatment changes were based on physician decisions and patient preferences. Demographic data including age, sex, body mass index (BMI), ethnicity, smoking history, and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence. RESULTS: A total of 2301 PsA patients with 2958 treatment periods were identified and included in the analyses. Mean age of the study population was 50.9 ± 14 years, 54% were females, 70.4% were with BMI > 25, 40% were current smokers, and 76% were with a Charlson comorbidity index > 1. The most commonly prescribed drug was etanercept (33%), followed by adalimumab (29%), golimumab (12%), secukinumab (10%), ustekinumab (8%), and infliximab (8%). While approximately 40% of patients persisted on therapy following 20 months of treatment, only about 20% of patients remained on any particular biologic agent after 5 years. Analyzing the data for all treatment periods while taking into account all lines of therapy revealed that secukinumab had a higher persistency than adalimumab, infliximab, and ustekinumab, with a log rank of 0.022, 0.047, and 0.001, respectively. Female sex and smoking were associated with lower drug persistence (HR = 1.25, 95% CI = 1.13-1.38 and HR = 1.109, 95% CI = 1.01-1.21, respectively). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-tumor necrosis factor-alpha (anti-TNFα) agent was observed, while secukinumab was found to be superior as second line therapy to adalimumab, etanercept, infliximab, and ustekinumab but not to golimumab with a log rank P value of 0.001, 0.004, 0.025, and 0.002, respectively. CONCLUSIONS: In this large observational cohort studied in the era of biologic therapy, a relatively low drug persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents was found to be more persistent than others as first line therapy, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.