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1.
Arthritis Res Ther ; 26(1): 130, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997725

RESUMO

BACKGROUND: The aim of this prospective observational cohort study was to unveil the predictors of treatment response to tocilizumab (TCZ) therapy in rheumatoid arthritis (RA) patients, in terms of clinical characteristics and serum proinflammatory cytokines, especially to explore the predictive value of granulocyte macrophage-colony stimulating factor (GM-CSF). METHODS: Active adult RA patients with inadequate response to MTX intending to receive TCZ therapy were recruited prospectively in the study. A total of 174 severe RA patients were included for the identification of the associations between treatment response and the following characteristic features: demographics, medications, disease activity, serum proinflammatory cytokines and so on. RESULTS: Disease duration (OR = 0.996), tender joint count (TJC)/68 (OR = 0.943), neutrophil ratio (W4/baseline) (OR = 0.224), the high level of GM-CSF > 5 ng/ml (OR = 0.414) at baseline were the independent adverse predictors of good response assessed by clinical disease activity index (CDAI) at week 24 (W24) for TCZ therapy in RA patients. Moreover, DAS28-ESR (OR = 2.951, P = 0.002) and the high level of GM-CSF > 10 ng/ml at baseline (OR = 5.419, P = 0.002) were independent predictors of poor response, but not the high level of GM-CSF > 5 ng/ml (OR = 2.713, P = 0.054). The patients in the high GM-CSF group had significantly higher DAS28-ESR and serum levels of cytokines (IL-17A, IL-1ß, IL-6, TNF-α) at baseline, as well as significantly higher rate of non-good response (62.8% vs. 39.4%, P = 0.010) and poor response (27.9% vs. 9.1%, P = 0.004) than the low GM-CSF group at W24. In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1ß at baseline than those in moderate and good response groups, while serum levels of IL-6 and TNF-α at baseline were not significantly different in three response groups. CONCLUSION: The high levels of GM-CSF (> 5 ng/ml and > 10 ng/ml) at baseline were the independent predictors of non-good response and poor response to TCZ at W24 respectively. The high level of GM-CSF at baseline is a marker of high disease activity and a predictor of poor response to TCZ in severe RA patients, which may facilitate the development of individualized treatment strategies for refractory RA.


Assuntos
Anticorpos Monoclonais Humanizados , Antirreumáticos , Artrite Reumatoide , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Feminino , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Adulto , Estudos de Coortes , Idoso , Biomarcadores/sangue , Valor Preditivo dos Testes
2.
Int J Rheum Dis ; 27(7): e15199, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39010815

RESUMO

AIM: To evaluate real-world abatacept retention and clinical outcomes in patients with rheumatoid arthritis in Taiwan. METHODS: This prospective, observational study enrolled patients with rheumatoid arthritis aged ≥20 years who received abatacept in real-world practice. The primary endpoint was the abatacept retention rate at 24 months. Patients were categorized into subgroups based on abatacept treatment status and previous biological disease-modifying antirheumatic drug (bDMARD) therapy. Risk factors affecting abatacept retention were determined by regression analysis. RESULTS: A total of 212 patients were enrolled. The overall abatacept retention rate at 24 months among all patients was 59.9% (95% confidence interval 53.0%-66.6%). Patients who were ongoing users of abatacept and bDMARD-naïve had the highest retention rate (76.3%); of these, 31.6% achieved low disease activity or remission after 2 years. Previous treatment with bDMARDs was associated with an increased risk of abatacept discontinuation (hazard ratio 1.99; p = .002). The most common reasons for abatacept discontinuation were drug switch (11.3%) and loss to follow-up (6.1%). Abatacept was well-tolerated with no new safety signals. CONCLUSION: The 24-month retention rate of abatacept was 59.9%; abatacept was associated with improved clinical outcomes and was well-tolerated in the real-world setting in Taiwan.


Assuntos
Abatacepte , Antirreumáticos , Artrite Reumatoide , Indução de Remissão , Humanos , Abatacepte/uso terapêutico , Abatacepte/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Taiwan/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Resultado do Tratamento , Estudos Prospectivos , Fatores de Tempo , Idoso , Fatores de Risco , Adulto , Substituição de Medicamentos , Adesão à Medicação
5.
RMD Open ; 10(3)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004432

RESUMO

BACKGROUND: The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1).To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE). METHODS: This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V (NCT02696785), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data. RESULTS: Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52. CONCLUSION: This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52. TRIAL REGISTRATION NUMBER: NCT02696785.


Assuntos
Anticorpos Monoclonais Humanizados , Espondiloartrite Axial , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Masculino , Resultado do Tratamento , Adulto , Pessoa de Meia-Idade , Espondiloartrite Axial/tratamento farmacológico , Espondiloartrite Axial/etiologia , Antirreumáticos/uso terapêutico , Antirreumáticos/administração & dosagem , Índice de Gravidade de Doença , Radiografia
6.
Adv Rheumatol ; 64(1): 52, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987832

RESUMO

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.


Assuntos
Doença de Raynaud , Reumatologia , Escleroderma Sistêmico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Humanos , Brasil , Reumatologia/normas , Doença de Raynaud/tratamento farmacológico , Sociedades Médicas , Doenças Pulmonares Intersticiais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Rituximab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera Cutânea/etiologia , Antirreumáticos/uso terapêutico
7.
Front Immunol ; 15: 1391848, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983856

RESUMO

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.


Assuntos
Artrite Reumatoide , Perfilação da Expressão Gênica , Transcriptoma , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Humanos , Antirreumáticos/uso terapêutico , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Biomarcadores , Linfócitos T CD8-Positivos/imunologia
8.
Reumatol Clin (Engl Ed) ; 20(6): 312-319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38991825

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) is the first-line treatment for systemic lupus erythematosus (SLE); however, there is heterogeneity in its clinical use. This consensus aims to bridge the gap in SLE treatment by providing practical and valuable recommendations for health professionals. METHODS: The methodology used is based on a systematic literature review and a nominal group technique (NGT). A ten-member scientific committee formulated eight clinically relevant questions. First, a systematic review was conducted to identify the available evidence, which the scientific committee evaluated to developed recommendations based on their expertise, achieving consensus through NGT. RESULTS: 1673 titles and abstracts were screened, and 43 studies were included for meeting the inclusion criteria. The scientific committee established 11 recommendations for HCQ use in initiation, maintenance, and monitoring, considering benefits and potential adverse effects of HCQ. Unanimous agreement was achieved on all recommendations. CONCLUSIONS: The available evidence supports HCQ's effectiveness and safety for SLE. Individualized assessment of the initial HCQ dose is important, especially in situations requiring dose reduction or discontinuation. This risk-benefit assessment, specifically focusing on the balance between retinal toxicity and the risk of SLE relapse, should guide decisions regarding medication withdrawal, considering disease activity, risk factors, and HCQ potential benefits. Close monitoring is essential for optimal disease management and minimize potential risks, such as QT prolongation or retinal toxicity.


Assuntos
Antirreumáticos , Hidroxicloroquina , Lúpus Eritematoso Sistêmico , Humanos , Antirreumáticos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Consenso
9.
Molecules ; 29(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38999143

RESUMO

OBJECTIVE: To elucidate the chemical profile of Xanthocerais lignum's extracts of different polarities and their impact on rheumatoid arthritis (RA), we identified anti-RA markers and predicted their action mechanisms. METHODS: A collagen-induced arthritis rat model was established, and UPLC-Q-Exactive Orbitrap MS technology was employed to analyze and identify the chemical constituents within the alcohol extract of Xanthocerais lignum and its various extraction fractions, as well as their translocation into the bloodstream. Serum spectrum-effect correlation analysis was utilized to elucidate the pharmacodynamic material basis of Xanthocerais lignum against RA and to screen for Q-Markers. Finally, the potential anti-RA mechanisms of the Q-Markers were predicted through compound-target interaction data and validated using molecular docking techniques. RESULTS: We identified 71 compounds, with flavan-3-ols and flavanones as key components. Of these, 36 were detected in the bloodstream, including 17 original and 19 metabolized forms. Proanthocyanidin A2, dihydroquercetin, catechin, and epicatechin (plus glucuronides) showed potential anti-RA activity. These compounds, acting as Q-Markers, may modulate ERK, NF-κB, HIF-1α, and VEGF in the HIF-1 pathway. CONCLUSIONS: This research clarifies Xanthocerais lignum's pharmacodynamic material basis against RA, identifies 4 Q-Markers, and offers insights into their mechanisms, aiding quality assessment and lead compound development for RA treatment.


Assuntos
Artrite Reumatoide , Biomarcadores , Simulação de Acoplamento Molecular , Extratos Vegetais , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/sangue , Artrite Reumatoide/metabolismo , Ratos , Biomarcadores/sangue , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/sangue , Artrite Experimental/metabolismo , Masculino , Modelos Animais de Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Antirreumáticos/farmacologia , Antirreumáticos/química , Antirreumáticos/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Ann Intern Med ; 177(7): JC79, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950394

RESUMO

SOURCE CITATION: Rech J, Tascilar K, Hagen M, et al. Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): a randomised, international, multicentre, double-blind, placebo-controlled trial. Lancet. 2024;403:850-859. 38364841.


Assuntos
Abatacepte , Antirreumáticos , Artrite Reumatoide , Inflamação , Abatacepte/uso terapêutico , Humanos , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Método Duplo-Cego , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
Clin Exp Pharmacol Physiol ; 51(8): e13906, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38965677

RESUMO

In this study, we wanted to investigate the effectiveness of combining disease-modifying anti-rheumatic drugs (DMARD) with hyperbaric oxygen therapy (HBOT) in reducing inflammation in a rheumatoid arthritis (RA) model using rats. We divided 56 male Sprague-Dawley rats into seven groups and induced RA using complete Freund's adjuvant. Some groups received HBOT, whereas others were given etanercept or leflunomide. We started the treatment on the 10th day after inducing RA and continued it for 18 days. To evaluate the effectiveness of the treatments, we measured paw swelling and used X-rays to examine the joints before and after the treatment. We also analysed the levels of two inflammatory markers, tumour necrosis factor (TNF)-α and interleukin (IL)-1ß, using an enzyme-linked immunosorbent assay. Additionally, we conducted histological analysis and assessed the expressions of anti-IL-1ß and anti-TNF-α antibodies. All the treatment groups showed a significant decrease in arthritis scores, paw swelling and levels of TNF-α and IL-1ß. The X-ray images revealed improvements in joint structure, and the histopathological analysis showed reduced inflammation and collagen abnormalities. Combining DMARD with HBOT had similar effects to individual therapies, suggesting a cost-effective and potentially safer approach for improving outcomes in rats with RA.


Assuntos
Antirreumáticos , Artrite Reumatoide , Oxigenoterapia Hiperbárica , Interleucina-1beta , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa , Animais , Oxigenoterapia Hiperbárica/métodos , Masculino , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacologia , Artrite Reumatoide/terapia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Artrite Reumatoide/metabolismo , Ratos , Interleucina-1beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Modelos Animais de Doenças , Etanercepte/uso terapêutico , Etanercepte/farmacologia , Artrite Experimental/terapia , Artrite Experimental/patologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Leflunomida/uso terapêutico , Leflunomida/farmacologia
12.
Sci Rep ; 14(1): 15119, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956106

RESUMO

Analyze the relationship between genetic variations in the MTHFR gene at SNPs (rs1801131 and rs1801133) and the therapy outcomes for Iraqi patients with rheumatoid arthritis (RA). The study was conducted on a cohort of 95 RA Iraqi patients. Based on their treatment response, the cohort was divided into two groups: the responder (47 patients) and the nonresponder (48 patients), identified after at least three months of methotrexate (MTX) treatment. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to analyze the MTHFR variations, specifically at rs1801133 and rs1801131. Overall, rs1801131 followed both codominant and dominate models, in which in the codominant model, GG [OR (95% CI) 0.11 (0.022-0.553)] and TG [OR (95% CI) 0.106 (0.021-0.528)] predict responders compared to the TT genotype; meanwhile, for the dominate model, the presence of both GG and TG genotypes [OR (95% CI) 0.108 (0.023-0.507)] together predict responders compared to the TT genotype. The Ars1801133Grs1801131 haplotype was significantly associated with responders [OR (95% CI): 0.388 (0.208-0.723)], while the Grs1801133Trs1801131 haplotype was associated marginally with nonresponders [OR (95% CI) 1.980 (0.965-4.064)]. In the final multivariate analysis, GG/TGrs1801131 genotypes were independently related to responders after adjustment for patients, disease, and treatment characteristics, while TTrs1801131 genotypes were associated with nonresponders. The Iraqi RA patients showed genetic polymorphism in MTHFR gene rs1801131 with T carrier allele associated with nonresponders to MTX therapy. The rs1801131 followed both codominant and dominant models. The G-carried allele for rs1801131 showed an independent association with responder to MTX therapy after adjustment for patients, disease, and treatment characteristics.


Assuntos
Artrite Reumatoide , Metotrexato , Metilenotetra-Hidrofolato Redutase (NADPH2) , Polimorfismo de Nucleotídeo Único , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Metotrexato/uso terapêutico , Masculino , Feminino , Iraque , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Antirreumáticos/uso terapêutico , Genótipo
13.
Sci Rep ; 14(1): 15226, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956271

RESUMO

This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.2% for interleukin 6 (IL-6) inhibitors, 68.6% for Janus kinase (JAK) inhibitors, 65.8% for tumor necrosis factor (TNF) inhibitors, and 57.6% for cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig). The initial use of b/tsDMARDs and the use of IL-6 inhibitors in comparison to CTLA4-Ig emerged as a significant factor associated with the improvement of knee joint symptoms. Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig.


Assuntos
Abatacepte , Antirreumáticos , Artrite Reumatoide , Interleucina-6 , Inibidores do Fator de Necrose Tumoral , Humanos , Artrite Reumatoide/tratamento farmacológico , Feminino , Masculino , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Idoso , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Articulação do Joelho/efeitos dos fármacos , Adulto , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/farmacologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
PLoS One ; 19(7): e0306337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959249

RESUMO

OBJECTIVE: Patients living with rheumatologic diseases on disease-modifying antirheumatic drugs (DMARD) are at an increased risk of developing tuberculosis (TB). Current guidelines recommend screening for latent tuberculosis infection (LTBI) before initiating DMARD. However, data is lacking on the value of yearly screening for LTBI. METHODS: A retrospective chart review was conducted on adult patients (≥ 18 years) with rheumatologic disease on DMARD followed longitudinally in the outpatient rheumatology clinics between 2017-2021. Collected data included patient demographics, rheumatologic diagnosis, medications, TB-related risk factors, interferon gamma release assay (IGRA) results, LTBI diagnosis and treatment. Descriptive statistics were performed. RESULTS: Among 339 patients, 81 (23.9%) were male, 259 (76.4%) were white, and 93 (27.5%) were Latinx. Inflammatory arthritis (84.1%) was the most common rheumatic diagnosis. Common DMARD were JAK inhibitors (19.2%), TNF-alpha inhibitors (18.9%), and IL-17 A inhibitors (18.0%). Only 2 patients at baseline had positive IGRA, and both had a history of treated LTBI. Positive IGRA tests were recorded in 1 (0.7%), 3 (1.8%), 3 (1.3%), and 3 (1.1%) in the years 2018, 2019, 2020, and 2021, respectively. Four patients converted from negative to positive during serial yearly IGRA testing. After reviewing the IGRA test and TB risk factors, only one patient was considered newly diagnosed with LTBI, requiring 4 months of rifampin. CONCLUSION: In a non-endemic area, serial IGRA testing of low-risk patients on DMARD yielded very low rate of newly diagnosed LTBI. A targeted LTBI screening based on TB-related risk factors should be performed prior to IGRA testing rather than universal yearly screening in a non-endemic setting.


Assuntos
Antirreumáticos , Testes de Liberação de Interferon-gama , Tuberculose Latente , Programas de Rastreamento , Doenças Reumáticas , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Masculino , Feminino , Testes de Liberação de Interferon-gama/métodos , Pessoa de Meia-Idade , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/complicações , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Estudos Retrospectivos , Adulto , Programas de Rastreamento/métodos , Idoso , Fatores de Risco
15.
Pharmacol Res Perspect ; 12(4): e1240, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38970433

RESUMO

Data on the use of golimumab (GLM) during pregnancy are limited. This study evaluated pregnancy outcomes in women treated with GLM during pregnancy. Cumulative data on GLM-exposed pregnancies from the Company's global safety database (GSD) are summarized. Cases were medically confirmed maternal exposures to GLM during pregnancy or within 3 months prior to conception with a reported pregnancy outcome. Pregnancy outcomes (e.g., live births) and congenital anomalies in prospectively reported cases (i.e., pregnancy outcome not known when first reported to the company) are presented in a descriptive manner. As of May 31, 2022, 261 prospectively reported pregnancies exposed to GLM were reported in the GSD: 214 (82.0%) live births (including six sets of twins), 31 (11.9%) spontaneous abortions (including one set of twins), 13 (5.0%) induced/elective abortions, 2 (0.8%) reported intrauterine death/still birth, and 1 (0.4%) fetal adverse event in an ongoing pregnancy. The majority of pregnancies had exposure to GLM at least in the first trimester of pregnancy. In total, seven congenital anomalies (7/261; 2.7%) were reported. Of these seven congenital anomalies, five were considered major according to EUROCAT classification version 1.4. Among the five prospectively reported congenital anomalies noted in live births (5/214; 2.3%), four were classified as major (4/214; 1.8%). The rates of adverse pregnancy outcomes and major congenital anomalies in prospectively reported pregnancy cases with exposure to GLM in the Company's GSD were consistent with published background rates for the general population.


Assuntos
Anormalidades Induzidas por Medicamentos , Anticorpos Monoclonais , Bases de Dados Factuais , Resultado da Gravidez , Gravidez , Feminino , Humanos , Anticorpos Monoclonais/efeitos adversos , Adulto , Resultado da Gravidez/epidemiologia , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/induzido quimicamente , Antirreumáticos/efeitos adversos , Adulto Jovem , Estudos Prospectivos , Nascido Vivo/epidemiologia
16.
Pediatr Rheumatol Online J ; 22(1): 63, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965620

RESUMO

BACKGROUND: The World Health Organisation Essential Medicines List (WHO EML) guides National Essential Medicines Lists and Standard Treatment Guidelines for clearly identified disease priorities especially in low- and middle-income countries. This study compares the degree to which the basket of medicines recommended for rheumatic diseases in children and young people in National Essential Medicines Lists of countries in the WHO Africa region, corresponds to the 2021 WHO EML and WHO EML for children, as a proxy of availability. METHODS: An online search of the WHO medicines and health technology portal, the Health Ministry websites of the 54 African countries, PUBMED and Google Scholar, with search terms for 'National Essential Medicines List', AND/OR 'standard treatment guidelines' AND/OR 'Lista Nacional de Medicamentos Essenciais' AND/ OR 'Liste Nationale de Medicaments Essentiels' AND Africa AND/OR < Name of African country > was conducted. The number of medicines on the national lists were compared according to a predefined template of medicines; and the percentage similarity calculated. Descriptive statistics were derived using STATA. RESULTS: Forty-seven countries in the WHO Africa region have developed a National Essential Medicines List. Eleven countries do not have any medicines listed for rheumatic diseases. The majority of countries had less than or equal to 50% similarity with the WHO EML for rheumatic disease in children and young people, median 3 medicines (IQR 1- 4). The most common medicines on the national lists from Africa were methotrexate, sulfasalazine and azathioprine, with etanercept available in 6 countries. Seven countries had only one medicine, acetylsalicylic acid listed in the section 'Juvenile Joint diseases'. A multiple linear regression model for the predictors of the number of medicines on the national lists established that 20% of the variability was predicted by health expenditure per capita, socio-demographic index and the availability of rheumatology services (adult and/or paediatric) p = 0.006, with socio-demographic index (p = 0.035, 95% CI 0.64-16.16) and the availability of rheumatology services (p = 0.033, 95% CI 0.13 - 2.90) significant. CONCLUSION: Four countries (8.5%) in Africa have updated their National Essential Medicines Lists to reflect adequate care for children and young people with rheumatic diseases. Moving forward, efforts should focus on aligning available medicines with the WHO EML, and strengthening healthcare policy for rheumatology and pharmaceutical services, for affordable access to care and medicines.


Assuntos
Medicamentos Essenciais , Doenças Reumáticas , Organização Mundial da Saúde , Humanos , Medicamentos Essenciais/provisão & distribuição , Medicamentos Essenciais/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , África , Criança , Adolescente , Antirreumáticos/uso terapêutico , Antirreumáticos/provisão & distribuição
17.
Medicine (Baltimore) ; 103(27): e38740, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968492

RESUMO

While biological disease-modifying anti-rheumatic drugs (bDMARDs) are considered beneficial for preventing osteoporosis and bone fracture, it is unclear whether bone loss is involved in the development of vertebral fracture, and few reports have examined the factors related to vertebral fracture in rheumatoid arthritis (RA) patients using bDMARDs. This study aims to identify factors influencing vertebral fracture in RA patients treated with bDMARDs. We retrospectively examined the records of 129 RA patients treated with bDMARDs for over 5 years. The lumbar spine and femoral bone mineral density, Disease Activity Score-28-C-Reactive Protein (DAS28-CRP) value, Simplified Disease Activity Index (SDAI), and modified Health Assessment Questionnaire (mHAQ) score were evaluated. The frequency of new vertebral fracture during the study and their risk factors were investigated. A comparison between the fracture group and the nonfracture group was performed. Multivariate analysis was performed using logistic regression analysis to detect risk factors for new vertebral fracture. The number of patients with new vertebral fracture during follow-up was 15 (11.6%) of the 129 patients in the study. Age and mHAQ score were significantly higher and lumbar spine and femoral neck bone mineral density were significantly lower in the fracture group than the nonfracture group. The risk factors for new vertebral fracture during the disease course were older age and higher mHAQ score indicating no remission over the 5 years of follow-up. In this study, there was no significant difference in disease indices such as the DAS28-CRP value and the SDAI between the fracture and nonfracture groups, suggesting an effective control of RA with bDMARDs. However, age and the mHAQ score, an index of RA dysfunction, were significantly higher in the fracture group. These results suggest that improving functional impairment may be important to prevent vertebral fracture in patients using bDMARDs.


Assuntos
Antirreumáticos , Artrite Reumatoide , Densidade Óssea , Fraturas da Coluna Vertebral , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Masculino , Feminino , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controle , Fraturas da Coluna Vertebral/epidemiologia , Fatores de Risco , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Estudos Retrospectivos , Idoso , Densidade Óssea/efeitos dos fármacos , Vértebras Lombares , Fatores Etários , Adulto
18.
PLoS One ; 19(7): e0306714, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38990897

RESUMO

BACKGROUND: Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. METHODS: We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. RESULTS: Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). CONCLUSIONS: In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.


Assuntos
Artrite Reumatoide , Azetidinas , Inibidores de Janus Quinases , Piperidinas , Purinas , Pirazóis , Sulfonamidas , Humanos , Artrite Reumatoide/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Azetidinas/uso terapêutico , Azetidinas/efeitos adversos , Estudos Retrospectivos , Idoso , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Purinas/uso terapêutico , Purinas/efeitos adversos , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Triazóis/uso terapêutico , Triazóis/efeitos adversos , Fatores de Risco , Adulto , Piridinas
19.
Front Immunol ; 15: 1398314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979406

RESUMO

The treatment of patients with rheumatoid arthritis (RA) has dramatically changed in the past 30 years. Currently, numerous conventional, biologic, and targeted synthetic DMARDs have been licensed and used following recommendations provided by international and national scientific societies. However, the availability of biosimilars and the increasing necessity of savings impacted on the local/national prescription of these drugs. The information provided by data sheet of every single drug is a decisive factor on the choice of a certain treatment merged with the patient's profile. Thus, our purpose was to construct a rational algorithm for the treatment strategy in RA according to costs and the product leaflet of the biologic and targeted-synthetic DMARDs currently licensed in Italy. We used the most recent available recommendations and then we performed a review of the literature considering all the factors that are known to influence drug safety/effectiveness. All these factors were considered in the context of the data sheets of currently available originators and biosimilars.


Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Humanos , Algoritmos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/efeitos adversos , Rotulagem de Medicamentos , Itália
20.
Lupus Sci Med ; 11(2)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977356

RESUMO

OBJECTIVES: Hydroxychloroquine (HCQ) has been shown to reduce thrombotic events in patients with SLE. However, the antiplatelet effects of HCQ are only supported by the platelet aggregation assay, which is a non-physiological test. The total thrombus-formation analysis system (T-TAS) is a microchip-based flow chamber system that mimics physiological conditions and allows for the quantitative analysis of thrombogenicity. The present study investigated the antiplatelet effects of HCQ using T-TAS. METHODS: This was a single-centre cross-sectional study on 57 patients with SLE. We measured the area under the pressure curve for 10 min (PL-AUC10) and the time to 10 kPa (T10) in patients with SLE using T-TAS and examined their relationships with the use of HCQ. PL-AUC10 and platelet aggregation were also measured at several HCQ concentrations using blood samples from healthy donors. RESULTS: PL-AUC10 was significantly lower in the HCQ/real body weight (RBW) ≥5 mg/kg group than in the <5 mg/kg group, while T10 was similar, indicating that HCQ inhibited overall thrombus formation rather than the initiation of thrombus formation. The antiplatelet effects of HCQ were initially detected at HCQ/RBW of approximately 4 mg/kg and reached a plateau at around 5.5 mg/kg. The administration of HCQ/RBW >4.6 mg/kg clearly exerted antiplatelet effects. Additionally, HCQ inhibited thrombus formation in T-TAS and the platelet aggregation response to epinephrine in a dose-dependent manner. CONCLUSIONS: We demonstrated the antiplatelet effects of HCQ under conditions simulating the physiological environment by using T-TAS and identified the range of doses at which HCQ exerted antiplatelet effects.


Assuntos
Hidroxicloroquina , Lúpus Eritematoso Sistêmico , Inibidores da Agregação Plaquetária , Agregação Plaquetária , Trombose , Humanos , Hidroxicloroquina/uso terapêutico , Feminino , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/sangue , Masculino , Agregação Plaquetária/efeitos dos fármacos , Adulto , Estudos Transversais , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/prevenção & controle , Trombose/etiologia , Trombose/tratamento farmacológico , Pessoa de Meia-Idade , Adulto Jovem , Testes de Função Plaquetária/métodos , Antirreumáticos/uso terapêutico
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