摘要
Thiopurine analogs and anti-tumor necrosis factor(TNF)agents have dramatically changed the therapeutics of inflammatory bowel diseases(IBD),improving short and long-term outcomes.Unfortunately some patients do not respond to therapy and others lose response over time.The pharmacokinetic properties of these drugs are complex,with high inter-patient variability.Thiopurine analogs are metabolized through a series of pathways,which vary according to the patients’pharmacogenetic profile.This profile largely determines the ratios of metabolites,which are in turn associated with likelihoods of clinical efficacy and/or toxicity.Understanding these mechanisms allows for manipulation of drug dose,aiming to reduce the development of toxicity while improving the efficacy of treatment.The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables.Several factors may alter drug clearance,including the concomitant use of immunomodulators(thiopurine analogs and methotrexate),systemic inflammation,the presence of anti-drug antibodies,and body mass.The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications,with good evidence for improvement in patient outcomesobserved when measuring metabolic pathway indices.The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care.
Thiopurine analogs and anti-tumor necrosis factor (TNF) agents have dramatically changed the therapeutics of inflammatory bowel diseases (IBD), improving short and long-term outcomes. Unfortunately some patients do not respond to therapy and others lose response over time. The pharmacokinetic properties of these drugs are complex, with high inter-patient variability. Thiopurine analogs are metabolized through a series of pathways, which vary according to the patients’ pharmacogenetic profile. This profile largely determines the ratios of metabolites, which are in turn associated with likelihoods of clinical efficacy and/or toxicity. Understanding these mechanisms allows for manipulation of drug dose, aiming to reduce the development of toxicity while improving the efficacy of treatment. The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables. Several factors may alter drug clearance, including the concomitant use of immunomodulators (thiopurine analogs and methotrexate), systemic inflammation, the presence of anti-drug antibodies, and body mass. The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications, with good evidence for improvement in patient outcomes observed when measuring metabolic pathway indices. The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care.
