Thiopurines have been associated with both clinical improvement and mucosal healing in treating Crohn disease (CD). Unfortunately, the high rate of adverse events (AEs) leading to drug withdrawal represents a major limitation in the use of these drugs.To evaluate the safety of thiopurines in patients with CD. To identify predictive factors associated with the development of thiopurine-induced A...

BACKGROUND Polymorphic thiopurine S-methyltransferase (TPMT) is a major determinant of thiopurine toxicity. METHODS We extracted 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) from erythrocytes with perchloric acid and converted them to 6-thioguanine (6-TG) and a 6-methylmercaptopurine (6-MMP) derivative during a 60-min acid hydrolysis step. The liquid chr...

BACKGROUND AND AIMS Methotrexate [MTX] is an immunomodulating drug that can be used to maintain remission in patients with Crohn's disease [CD], but data on efficacy and tolerability in children and teenagers are scarce. We evaluated the long-term efficacy and tolerability of MTX monotherapy after thiopurine therapy in paediatric CD patients. METHODS A multicenter cohort of paediatric MTX use...

AIM To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. METHODS We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. RESULTS Among 51 patients who...

Azathioprine (AZA) is frequently used in patients with inflammatory bowel disease (IBD). However, toxic adverse reactions frequently develop and limit the clinical benefits. Currently, the precise mechanisms underlying thiopurine-related toxicity are not well understood. To investigate the relationship between the extent of thiopurine metabolism and adverse reactions in Japanese IBD patients, w...

BACKGROUND & AIMS There is controversy over whether the treatment of patients with ulcerative colitis (UC) with thiopurines increases their risk of lymphoma. We evaluated the risk of lymphoma (ongoing, residual, and per year of therapy) among thiopurine-treated patients with UC. METHODS We obtained nationwide data from the Veterans Affairs (VA) health care system from 2001 to 2011. We perform...

The compounds cis-6-(2-acetylvinylthio)purine (cis-AVTP) and trans-6-(2-acetylvinylthio)guanine (trans-AVTG) are glutathione-activated prodrugs of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), respectively, that have comparable or lower IC50 values in tumor cells than 6-MP and 6-TG. Previously, we showed that cis-AVTP- and trans-AVTG-treated mice exhibited less bone marrow and intestinal to...

BACKGROUND AND AIMS A pre-treatment determination of the thiopurine S-methyltransferase (TPMT) genotype or phenotype can identify patients at risk of developing severe adverse reactions from thiopurine treatment. The risk of misclassifying a patient might be dependent on the method used. The aim of this study was to investigate the concordance between TPMT genotyping and phenotyping. METHODS ...