RESUMO
OBJECTIVES: To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. METHODS: Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients. RESULTS: We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P <0.001), with 6/12/24-months' BASDAI < 2 (P ≤0.002) and ASDAS < 1.3 (P ≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P ≤0.04) and DAPSA28 ≤ 4 (P ≤0.01), but not DAS28CRP(3)<2.6 (P ≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. CONCLUSION: High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.
Assuntos
Artrite Psoriásica/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Índice de Gravidade de Doença , Espondilartrite/tratamento farmacológico , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Indução de Remissão , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
OBJECTIVE: To determine the reproducibility of evaluation of sacroiliac joint (SIJ) radiographs among readers with varying levels of experience, and to identify potential drivers of disagreement in classification among 5 predefined radiographic lesion types. METHODS: The study sample consisted of 104 consecutive patients aged 18-40 with low back pain ≥ 3 months of duration who met the Assessment of SpondyloArthritis international Society (ASAS) definition for a positive SIJ magnetic resonance image, or were HLA-B27-positive and had ≥ 1 spondyloarthritis (SpA)-related clinical/laboratory feature according to the ASAS classification criteria for axial SpA. Seven blinded readers (2 musculoskeletal radiologists, 5 rheumatologists) classified pelvic radiographs according to the modified New York criteria (mNY) and recorded presence/absence of 5 lesion types in both SIJ: erosion, sclerosis, ankylosis, joint space widening, and joint space narrowing. Reproducibility of mNY classification among 21 reader pairs was assessed and potential drivers of disagreement were identified among 5 lesion types. A generalized linear mixed logistic regression model served to analyze to what extent discordance in lesion type was associated with discrepant mNY classification. RESULTS: Mean κ values (percent concordance) were 0.39 (84.1%) for mNY classification over 21 reader pairs, 0.46 (79.8%) between 2 musculoskeletal radiologists, and 0.55 (86.5%) and 0.36 (77.9%) between the most experienced rheumatologist and the 2 radiologists. Erosion showed the lowest agreement (25%) among patients with discordant classification and gave the highest OR of 13.5 for disagreement. CONCLUSION: Reproducibility of radiographic SIJ classification in an SpA inception cohort was only fair to at best moderate among 7 readers with varying levels of experience, questioning the applicability of mNY in early SpA.
Assuntos
Dor nas Costas/diagnóstico por imagem , Articulação Sacroilíaca/diagnóstico por imagem , Sacroileíte/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Adolescente , Adulto , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Reprodutibilidade dos Testes , Adulto JovemRESUMO
RNA-seq is a sensitive and accurate technique to compare steady-state levels of RNA between different cellular states. However, as it does not provide an account of transcriptional activity per se, other technologies are needed to more precisely determine acute transcriptional responses. Here, we have developed an easy, sensitive and accurate novel computational method, IRNA-SEQ: , for genome-wide assessment of transcriptional activity based on analysis of intron coverage from total RNA-seq data. Comparison of the results derived from iRNA-seq analyses with parallel results derived using current methods for genome-wide determination of transcriptional activity, i.e. global run-on (GRO)-seq and RNA polymerase II (RNAPII) ChIP-seq, demonstrate that iRNA-seq provides similar results in terms of number of regulated genes and their fold change. However, unlike the current methods that are all very labor-intensive and demanding in terms of sample material and technologies, iRNA-seq is cheap and easy and requires very little sample material. In conclusion, iRNA-seq offers an attractive novel alternative to current methods for determination of changes in transcriptional activity at a genome-wide level.
Assuntos
Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA/métodos , Linhagem Celular , Imunoprecipitação da Cromatina/métodos , Imunoprecipitação da Cromatina/estatística & dados numéricos , Perfilação da Expressão Gênica/estatística & dados numéricos , Regulação da Expressão Gênica , Genoma Humano , Humanos , Íntrons , Análise de Sequência de RNA/estatística & dados numéricosRESUMO
OBJECTIVE: To characterize the impact of etanercept (ETN) in AS on cost, work productivity and quality of life (QoL). METHODS: A Phase 4, open-label, multi-centre (UK, Scandinavia) extension study in AS. Eligible subjects (n = 84) were treated for 36-52 weeks with ETN 50 mg s.c. once weekly. Analysis included direct costs (transformed out-patient and in-patient care elements), indirect costs (sick leave and lost working days), efficacy and QoL. RESULTS: Annualized direct and indirect costs decreased (55.5%, P ≤ 0.008) during ETN treatment, as did out-patient and in-patient episodes (physiotherapist/physician visits, P = 0.012). Work productivity and QoL increased. CONCLUSION: ETN therapy significantly reduces direct and indirect health-care costs and increases work ability and QoL in AS. Trial Registration. EUDRACT, https://eudract.ema.europa.eu/, 2006-001061-42.