Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three biological response modifiers that inhibit tumour necrosis factor-alpha (TNF-alpha) are approved for treating rheumatoid arthritis (RA). Etanercept is a fusion protein comprising two soluble human TNF-alpha receptors linked to the Fc fragment of human immunoglobulin G1. Infliximab is a chimeric (human/mouse) monoclonal antibody and adalimumab is a humanised monoclonal antibody. In placebo-controlled trials in established disease-modifying antirheumatic drug (DMARD)-refractory RA, the anti-TNF-alpha agents have reduced disease activity, as monotherapy or in combination with methotrexate. In long-term, open-label studies with etanercept or adalimumab, clinical response was sustained for up to 5 years. In early RA, etanercept has similar efficacy to methotrexate. However, etanercept was more effective than methotrexate in preventing radiographic progression. Preventing or delaying disease progression and disability with etanercept therapy in early RA may reduce costs associated with long-term disease outcomes. Data also suggest a benefit of infliximab plus methotrexate or adalimumab plus methotrexate in early RA. All three agents have been shown to improve functionality as assessed by health assessment questionnaire (HAQ) disability scores. Health-related quality of life is also improved in terms of physical and mental health and vitality. Furthermore, etanercept and adalimumab are associated with a reduction in fatigue. Long-term etanercept or infliximab therapy is associated with increased job employment and etanercept also reduces healthcare utilisation. Mild, transient injection-site reactions occur in about 33% of patients treated with etanercept and 20% of patients treated with adalimumab. In patients treated with infliximab, 16-20% have infusion reactions. The incidence of serious infection associated with etanercept and infliximab was low, about 2-3% in etanercept studies of up to 5 years duration, and 5% in a survey of more than 10 infliximab trials. This paper reviews the evidence for efficacy, safety and effectiveness of anti-TNF-alpha agents in RA.
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PMID:Drugs that block tumour necrosis factor: experience in patients with rheumatoid arthritis. 1515 3

Crohn disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by a relapsing course and variable presentation that often includes abdominal pain, diarrhea, and fatigue. CD frequently presents during childhood, resulting in pediatric-specific complications, such as growth failure and delayed puberty. Conventional drug therapy for moderate to severe pediatric CD includes induction of remission with corticosteroids, and maintenance of remission with immunomodulators. Patients who have an inadequate response to standard therapy are being increasingly treated with anti-tumor necrosis factor-alpha (TNFalpha) agents. Infliximab has been the most widely studied anti-TNFalpha agent in pediatric CD, and has been shown to be efficacious in this condition. Adalimumab has been proven to be efficacious in adults with CD, but there has been only a single case report in children. CDP571 has been tested in 20 children with CD, showing some efficacy. Finally, thalidomide therapy has been associated with improvement in two small case series. Toxicities of these agents include infusion reactions, infections, malignancies, neurologic disorders, and hematologic derangements.
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PMID:Managing Crohn disease in children and adolescents : focus on tumor necrosis factor antagonists. 1816 6

Data from a clinical study of 86 pancreatic cancer patients with involuntary, significant weight loss (cachexia) were used to explore the relationship between patient-reported outcomes (PROs) and survival. In all, 28 pancreatic cancer patients with cachexia were given gemcitabine (Gemzar) plus 3 mg/kg of infliximab (Remicade), 28 were given gemcitabine plus 5 mg/kg of infliximab, and 30 were given gemcitabine plus placebo in a double-blinded, phase II, multicenter trial. PRO endpoints included scores from the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Functional Assessment of Anorexia/ Cachexia Therapy (FAACT), Brief Pain Inventory (BPI), and the Short-Form 36 general health survey (SF-36). Population mean scores at baseline indicated fatigue problems (FACIT-F), nutritional health issues (FAACT), and mild-to-moderate pain (BPI "worst pain" score). Baseline normalized SF-36 values for physical functioning, vitality, and mental health indicated substantial impairment. Baseline fatigue and physical-functioning scores predicted survival as well as, or better than, baseline Karnofsky Performance Status or hemoglobin level. A cut-point in the FACIT-F score (median < or = 30) strongly predicted mortality; patients with greater fatigue had a lower median overall survival than did those with less fatigue. These findings supported several features of an a priori clinical-benefit model. Patient-reported fatigue provided powerful prognostic information; tracking of this symptom may be useful for treatment planning and medical monitoring of advanced-stage pancreatic cancer patients with cachexia. These results must be confirmed by larger trials.
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PMID:The prognostic significance of patient-reported outcomes in pancreatic cancer cachexia. 1872 39

Crohn's disease is a chronic inflammatory bowel disease characterized by transmural, granulomatous inflammation. In paediatric-onset Crohn's disease, the most frequent clinical features are abdominal pain, diarrhoea, fatigue and weight loss. Delayed puberty, growth retardation and osteoporosis might, however, be the predominant signs of the disease. This paper reports the case of a 13-year-old girl with Crohn's disease diagnosed at the age of 11 years, with classic gastrointestinal symptoms in the previous few months, but with severe osteoporosis at onset. The child has been on infliximab therapy for 1 year, with complete control of the disease. Therapy with infliximab appears to influence bone metabolism, bone formation and resorption, and that improvement seems to be independent of the clinical response to the drug. Infliximab has recently been approved for paediatric use, which has been a great improvement for a group of patients lacking therapeutic options.
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PMID:Crohn's disease in a child: unusual presentation with severe osteoporosis. 2117 34