title: Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease.
abstract: Improving the efficacy and reducing the toxicity of thiopurines and methotrexate (MTX) have been areas of intense basic and clinical research. An increased knowledge on pharmacodynamics and pharmacokinetics of these immunomodulators has optimized treatment strategies in inflammatory bowel disease (IBD). This review focuses on the metabolism and mode of action of thiopurines and MTX, and provides an updated overview of individualized treatment strategies in which efficacy in IBD can be increased without compromising safety. The patient-based monitoring instruments adapted into clinical practice include pretreatment thiopurine S-methyltransferase testing, thiopurine metabolite monitoring, and blood count measurements that may help guiding the dosage to improve clinical outcome. Other approaches for optimizing thiopurine therapy in IBD include combination therapy with allopurinol, 5-aminosalicylates, and/or biologics. Similar strategies are yet to be proven effective in improving the outcome of MTX therapy. Important challenges for the management of IBD in the future relate to individualized dosing of immunomodulators for maximal efficacy with minimal risk of side effects. As low-cost conventional immunomodulators still remain a mainstay in pharmacotherapy of IBD, more research remains warranted, especially to substantiate these tailored management strategies in controlled clinical trials.
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. mehmet.coskun@regionh.dk.|Department of Biology and Biotech Research and Innovation Centre (BRIC), The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark. mehmet.coskun@regionh.dk.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Steenholdt
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nanne K
authors.initials: NK
authors.lastname: de Boer
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008727:Methotrexate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D011687:Purines; D008727:Methotrexate