BIOMAT Database Logo BIOMAT Database Logo

Predictive Algorithm for Thiopurine-Induced Hepatotoxicity in Inflammatory Bowel Disease Patients. 2022

Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Department of Pharmacy, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands.

Approximately 25% of patients with inflammatory bowel disease (IBD) discontinue azathioprine (AZA) or mercaptopurine (MP) therapy within 3 months of treatment initiation because of adverse drug reactions. Of these side-effects, about half are because of hepatotoxicity. The aim of this study was to validate and (subsequently) optimize a previously reported predictive algorithm for thiopurine-associated hepatotoxicity by increasing the number of patients with IBD benefitting from conventional thiopurine therapy. This multicenter observational study included consecutive thiopurine-naive patients with IBD who received AZA or MP treatment. The primary outcome was hepatotoxicity within 12 weeks. The patients with and without hepatotoxicity were compared. Four determinants, namely, age, sex, body mass index (BMI), and 6-methylmercaptopurine ribonucleotide concentrations 1 week after treatment initiation (T = 1) were used to validate and optimize 2 (1 dichotomous and 1 continuous) algorithms using multivariable logistic regression analysis. Of 229 patients, 21 (9%) developed hepatotoxicity and 93% of the patients received MP with a median dose of 0.7 mg/kg (95% confidence interval 0.3-1.4 mg/kg). A difference in BMI was found between with and without hepatotoxicity groups (median 27.6 versus 24.2, P = 0.022). Specificities of 68% (Algorithm 1) and 77% (Algorithm 2) and sensitivities of 56% (Algorithm 1) and 50% (Algorithm 2) were obtained. Both algorithms demonstrated limited predictive accuracy for thiopurine-induced hepatotoxicity in the validation cohort. Relevant factors contributing to this outcome were changes in thiopurine prescription behavior over time, with more MP prescriptions at relatively lower dosages of MP.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D001379 Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed) Azathioprine Sodium,Azathioprine Sodium Salt,Azathioprine Sulfate,Azothioprine,Immuran,Imuran,Imurel,Sodium, Azathioprine
D015122 Mercaptopurine An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. 6-Mercaptopurine,1,7-Dihydro-6H-purine-6-thione,6-Mercaptopurine Monohydrate,6-Thiohypoxanthine,6-Thiopurine,6H-Purine-6-thione, 1,7-dihydro-,BW 57-323H,Leupurin,Mecaptopurine Anhydrous,Mercaptopurina Wellcome,Puri-Nethol,Purimethol,Purinethol,6 Mercaptopurine,6 Mercaptopurine Monohydrate,6 Thiohypoxanthine,6 Thiopurine,BW 57 323H,BW 57323H
D015212 Inflammatory Bowel Diseases Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS. Bowel Diseases, Inflammatory,Inflammatory Bowel Disease
D056486 Chemical and Drug Induced Liver Injury A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment. Drug-Induced Liver Injury,Liver Injury, Drug-Induced,Acute Liver Injury, Drug-Induced,Chemically-Induced Liver Toxicity,Drug-Induced Acute Liver Injury,Drug-Induced Liver Disease,Hepatitis, Drug-Induced,Hepatitis, Toxic,Liver Injury, Drug-Induced, Acute,Toxic Hepatitis,Acute Liver Injury, Drug Induced,Chemically Induced Liver Toxicity,Chemically-Induced Liver Toxicities,Disease, Drug-Induced Liver,Diseases, Drug-Induced Liver,Drug Induced Acute Liver Injury,Drug Induced Liver Disease,Drug Induced Liver Injury,Drug-Induced Hepatitides,Drug-Induced Hepatitis,Drug-Induced Liver Diseases,Drug-Induced Liver Injuries,Hepatitides, Drug-Induced,Hepatitides, Toxic,Hepatitis, Drug Induced,Injuries, Drug-Induced Liver,Injury, Drug-Induced Liver,Liver Disease, Drug-Induced,Liver Diseases, Drug-Induced,Liver Injuries, Drug-Induced,Liver Injury, Drug Induced,Liver Toxicities, Chemically-Induced,Liver Toxicity, Chemically-Induced,Toxic Hepatitides,Toxicities, Chemically-Induced Liver,Toxicity, Chemically-Induced Liver
D064420 Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals. Drug-Related Side Effects and Adverse Reaction,Adverse Drug Event,Adverse Drug Reaction,Drug Side Effects,Drug Toxicity,Side Effects of Drugs,Toxicity, Drug,Adverse Drug Events,Adverse Drug Reactions,Drug Event, Adverse,Drug Events, Adverse,Drug Reaction, Adverse,Drug Reactions, Adverse,Drug Related Side Effects and Adverse Reaction,Drug Related Side Effects and Adverse Reactions,Drug Side Effect,Drug Toxicities,Effects, Drug Side,Reactions, Adverse Drug,Side Effect, Drug,Side Effects, Drug,Toxicities, Drug

Related Publications

Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease.
February 2017, Alimentary pharmacology & therapeutics,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Thiopurine hepatotoxicity in inflammatory bowel disease: the role for adding allopurinol.
September 2008, Expert opinion on drug safety,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Predictive role of NUDT15 variants on thiopurine-induced myelotoxicity in Asian inflammatory bowel disease patients.
January 2018, Pharmacogenomics,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: a review.
July 2008, The American journal of gastroenterology,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Biomarkers Predictive of Response to Thiopurine Therapy in Inflammatory Bowel Disease.
January 2020, Frontiers in medicine,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
6-methylmercaptopurine-induced leukocytopenia during thiopurine therapy in inflammatory bowel disease patients.
June 2017, Journal of gastroenterology and hepatology,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Thiopurine therapy in inflammatory bowel disease.
October 2010, Expert review of gastroenterology & hepatology,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Thiopurine treatment in inflammatory bowel disease.
January 2007, Clinical pharmacokinetics,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Letter: thiopurine blood monitoring for patients with inflammatory bowel disease.
March 2012, Alimentary pharmacology & therapeutics,
Sofia A W van Moorsel, and Debbie S Deben, and Rob H Creemers, and Bjorn Winkens, and Paul Bus, and Marieke J Pierik, and Melek Simsek, and Nanne K H de Boer, and Adriaan A van Bodegraven, and Dennis R Wong
Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease.
February 2017, Journal of Crohn's & colitis,
Copied contents to your clipboard!