RESUMO
The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects.
Assuntos
Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Etanercepte/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Artrite Juvenil/genética , Artrite Juvenil/imunologia , Artrite Juvenil/patologia , Estudos de Casos e Controles , Criança , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
The primary aim of this study was to assess whether epoetin alpha (Ea) would improve cognitive performance in a group of anaemic cancer patients receiving chemotherapy. The secondary aim was to confirm the positive impact of Ea on haematological parameters, and quality of life (QOL). Fifty patients with solid tumours and haemoglobin (Hb) <11.0 g/dL received Ea 40,000 units once weekly for 12 weeks and were administered the Mini-Mental State Examination and the European Organization for Research and Treatment of Cancer (QLQ-C30) questionnaire prior to Ea therapy and at study completion. No clinically significant alterations were observed on cognitive function during Ea treatment. Changes in cognitive function were unrelated to Hb change and there were no significant differences in cognitive performance between Ea responders and non-responders. The analyses revealed clinically significant improvements in Hb levels, physical and role function, and clinically meaningful reductions in fatigue. Hb changes were significantly associated with the magnitude of improvement in QOL parameters. The lack of a clinical benefit in cognition observed in this study during Ea treatment may redirect the focus of research from enhancing to maintaining cognitive function, since stability in cognitive performance through time may be as well clinically important.
Assuntos
Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Transtornos Cognitivos/tratamento farmacológico , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Esquema de Medicação , Epoetina alfa , Fadiga/induzido quimicamente , Feminino , Hemoglobinas/efeitos dos fármacos , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Proteínas Recombinantes , Resultado do Tratamento , Adulto JovemRESUMO
Cholangiocarcinoma is one of the most aggressive malignancies. Patients with advanced or metastatic disease have a particularly dismal prognosis. The role of chemotherapy remains a matter of debate. A number of recent trials have shown that capecitabine in combination with other agents seems to be active as first-line treatment in advanced biliary cancer. Clinical data regarding the activity of capecitabine in pretreated patients are limited. In this report we describe a patient with previously treated, metastatic cholangiocarcinoma who developed stabilization of the disease for 7 months following chemotherapy with capecitabine. The patient had previously received 2 lines of chemotherapy. Capecitabine was tolerated fairly well without serious adverse events. We consider this observation to be important given the absence of active, non-surgical treatments in unresectable tumors.