Alimentary pharmacology & therapeutics
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Aliment. Pharmacol. Ther. · Aug 2007
Randomized Controlled Trial Multicenter StudyA randomized, double-blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn's disease.
Therapy targeted at tumour necrosis factor-alpha has an established role in Crohn's disease. Lenalidomide, an analogue of thalidomide, is an oral immunomodulatory agent with powerful antitumour necrosis factor-alpha properties. It is licensed for myeloma and myelodysplastic syndrome. Based upon reports of thalidomide efficacy, lenalidomide was evaluated in Crohn's disease. ⋯ Lenalidomide, an oral agent with antitumour necrosis factor-alpha properties, was not effective in active Crohn's disease in contrast to reports of benefit from thalidomide. The reasons for this lack of efficacy are speculative, other physiological activities may offset its action on inflammatory cytokines, or its antitumour necrosis factor-alpha action without apoptosis may be insufficient for activity in Crohn's disease.
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Since the seminal discovery of the HFE gene a decade ago, considerable further progress in unravelling the genetic basis of haemochromatosis has been made. Novel genes and iron overload phenotypes have been described with potential insights into the molecular pathophysiology of human iron metabolism. ⋯ Further identification of non-HFE genes associated with iron homeostasis will enhance our diagnostic certainty of primary haemochromatosis and may explain the variable expression seen in HFE-related disease. Improving our understanding of the mechanisms of iron regulation may lead to novel therapeutic strategies for the management of iron overload.