ObjectiveTo analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial.MethodsMBDA scores (scale 1–100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse.ResultsModerate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA−/ACPA−, moderate in patients who were MBDA+/ACPA− (33.3%) and MBDA−ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%).ConclusionsMBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients.Trial registration numberEudraCT 2009-015740-42.
Objectives: To analyze glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with glucocorticoid receptor alpha-isoform (GRα) gene expression. Methods: We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRα expression in mononuclear cells. Results: Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRα expression was similar among groups. In the RA group there was an inverse correlation between GRα expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRα expression. Conclusions: Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRα gene expression, since it was similar among groups and GRα increased with disease activity. Arq Bras endocrinol metab. 2009;53(1):24-30.
KeywordsGlucocorticoid receptors; rheumatoid arthritis; dexamethasone suppression test resuMo Objetivos: Determinar a sensibilidade aos glicocorticóides (GC) utilizando teste de supressão com dexametasona em doses muito baixas (IV-VLD-DST) em pacientes com artrite reumatóide (AR) e sua correlação com a expressão gênica da isoforma alfa do receptor glicocorticóide (GRα). Métodos: Foram avaliados 20 controles saudáveis e 32 pacientes com AR com Health Assessment Questionnaire (HAQ) e Disease Activity Score 28 joints (DAS), IV-VLD-DST e expressão do GRα em células mononucleares. Resultados: Cortisol basal e porcentagem de redução do cortisol após IV-VLD-DST foram menores no grupo AR do que nos controles, enquanto a expressão de GRα foi similar entre eles. No grupo com AR, ocorreu correlação negativa entre a expressão do GRα e a porcentagem de supressão do cortisol, enquanto nos controles não houve correlação. Ocorreu relação direta entre DAS e expressão de GRα. Conclusões: Sugerimos que os mecanismos envolvidos na resistência aos GC observada na AR não estejam ao nível da expressão gênica do GRα, já que esta é igual entre os grupos e aumenta com a gravidade da doença. It is characterized by synovial membrane inflammation due to proliferation and infiltration of lymphocytes that determine progressive destruction of cartilage and subchondral bone (1,2). Transcription factors, such as activator protein (AP)-1 and nuclear factor kappa-B (NF-κB), determine greater expression of pro-inflammatory cytokines, COX-2, growth factors, acute phase proteins and adhesion molecules (3-6). The expression of NF-κB is increased in RA and seems to be one of the main factors involved in the pathogenesis of the disease (7,8).Glucocorticoids (GCs) activate the cytosolic glucocorticoid receptor (GR), which translocates to the nucleus to regulate target-gene transcription and determines the reduction of synthesis and release of pro-inflamma...
Background/Aims: The wide variability of responses to corticotherapy suggests a role for individual recognition of steroid sensitivity in order to customize treatment. Oral dexamethasone (DEX) administration may be hindered by the rate of its intestinal absorption and the liver first-passage effect. In this study we suggest that an intravenous very low dose DEX suppression test (VLD IV-DST) can be used as an index for glucocorticoid (GC) sensitivity. Methods: We evaluated 87 normal subjects: 44 prepubertal children, 23 adolescents and 20 adults with a VLD IV-DST using 20 µg/m2 of DEX (dose able to recognize GC sensitivity). Cortisol was initially measured at several time-points after DEX prompting us to establish its nadir and subsequent simplification of the test by measuring cortisol at baseline and after 120 min. Results: Baseline cortisol was similar in adolescents and in adults, but lower in children. There was a spectrum of individual responses in all age groups. The percent reduction of cortisol after 120 min was different in these three age groups, with median values of 44.4% in children, 25.9% in adolescents and 61.6% in adults. Conclusion: This simplified VLD IV-DST using 20 µg/m2 of DEX is useful to evaluate individual sensitivity to GC in different age groups.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.