Pharmacology and optimization of thiopurines and methotrexate in inflammatory bowel disease
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Pharmacology and optimization of thiopurines and methotrexate in inflammatory bowel disease. / Coskun, Mehmet; Steenholdt, Casper; de Boer, Nanne K.; Nielsen, Ole Haagen.
In: Clinical Pharmacokinetics, Vol. 55, No. 3, 2016, p. 257-274.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Pharmacology and optimization of thiopurines and methotrexate in inflammatory bowel disease
AU - Coskun, Mehmet
AU - Steenholdt, Casper
AU - de Boer, Nanne K.
AU - Nielsen, Ole Haagen
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1007/s40262-015-0316-9
DO - 10.1007/s40262-015-0316-9
M3 - Journal article
C2 - 26255287
VL - 55
SP - 257
EP - 274
JO - Clinical Pharmacokinetics
JF - Clinical Pharmacokinetics
SN - 0312-5963
IS - 3
ER -
ID: 154217762