Pharmacogenetics is one of the first clinical applications of the postgenomic era; it studies the role of heritability of drug responses. It promises personalised medicine rather than the established ‘one size fits all’ approach to drugs and dosages. This should ultimately lead to more efficient and safer drug therapy. In recent years, pharmacogenetic information has been included in drug label...

Multilocus genotypes have been shown to be of relevance for using pharmacogenomic principles to individualize drug therapy. As it relates to thiopurine therapy, genetic polymorphisms of TPMT are strongly associated with the pharmacokinetics and clinical effects of thiopurines (mercaptopurine and azathioprine), influencing their toxicity and efficacy. We have recently demonstrated that TPMT and ...

BACKGROUND Thiopurines are used for many cancers, including acute lymphoblastic leukemia (ALL). Patients with an inherited host defect in thiopurine methyltransferase (TPMT) are at high risk for life-threatening toxicity if treated with conventional dosages, but the impact on antileukemic efficacy is less clear. MATERIALS AND METHODS We treated thiopurine-sensitive BCR-ABL+Arf-null Tpmt+/+ AL...

When treating Crohn disease (CD) with thiopurines, achievement of an objective response is essential. However, the minimal degree of mucosal improvement required to alter disease outcomes of CD is unknown.To determine the endoscopic responses of thiopurine monotherapy and to determine the minimal degree of mucosal improvement required to alter disease outcomes of CD.One hundred thirty CD patien...

BACKGROUND In recent years several trials have addressed treatment challenges in Crohn's disease. Clinical trials however, represent a very special situation. AIMS To perform a cross-sectional survey among gastroenterologists on the current clinical real life therapeutic approach focussing on the use of biologics. METHODS A survey including six main questions on clinical management of loss ...

BACKGROUND Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a prospective observational cohort study. METHODS 19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified inflammatory bo...

Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. Over 20 variant TPMT-encoding alleles, which cause reduced enzymatic activity, have been discovered so far. Our aim was to investigate the frequencies of variant alleles, i.e. genotypes in inflammatory bowel disease (IBD) patients and healthy individuals and to compare these frequencies ...

BACKGROUND & AIMS The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC. METHODS ...