Carman Nicholas, Mack David R, Benchimol Eric I
CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
Curr Gastroenterol Rep. 2018 Apr 5;20(5):18. doi: 10.1007/s11894-018-0623-z.
Therapeutic drug monitoring (TDM) has emerged as a useful tool to optimize the use of drug therapies in adults with inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC), especially during the use of biological therapies, for which the pharmacokinetics and pharmacodynamics are highly variable among patients. Fewer data exist in children. This review examines the current literature on TDM in pediatric IBD.
Drug clearance is affected by a number of patient and disease factors. For thiopurines, adjusting dosing by monitoring 6-thioguanine (6TGN) and 6-methylmercaptopurine ((6MMP) levels is demonstrated to maximize response and minimize toxicity, while monitoring metabolite levels when treating with anti-tumor necrosis factor (anti-TNF) remain controversial. While in adults the use of TDM in the setting of loss of response to anti-TNF therapy is established, in children, only a small number of studies exist, but these too have encouraging results. There are however, conflicting data regarding the optimal timing of TDM, comparing "reactive" monitoring and "proactive" monitoring. No such data exist in pediatrics. TDM is cost-effective, and dose reduction may represent a safety benefit. There are limited adult data for use of TDM for the newer biologics, vedolizumab and ustekinumab, but early results suggest similarly promising utility. The use of TDM in pediatric IBD is increasing in clinical practice, with similar efficacy to adults demonstrated in children with loss of response to anti-TNF therapy. More prospective studies are needed in children to examine proactive monitoring and utility of TDM with newer biologics.
治疗药物监测（TDM）已成为优化炎症性肠病（IBD）成人患者药物治疗的有用工具，IBD包括克罗恩病（CD）和溃疡性结肠炎（UC），特别是在使用生物疗法期间，因为生物疗法的药代动力学和药效学在患者之间差异很大。儿童相关数据较少。本综述探讨了儿科IBD中TDM的当前文献。
药物清除受多种患者和疾病因素影响。对于硫嘌呤类药物，通过监测6-硫鸟嘌呤（6TGN）和6-甲基巯基嘌呤（6MMP）水平来调整剂量，已证明可使反应最大化并使毒性最小化，而在使用抗肿瘤坏死因子（抗TNF）治疗时监测代谢物水平仍存在争议。虽然在成人中，TDM在抗TNF治疗反应丧失的情况下的应用已得到确立，但在儿童中，仅有少数研究，不过这些研究也取得了令人鼓舞的结果。然而，关于TDM的最佳时机，比较“反应性”监测和“前瞻性”监测，存在相互矛盾的数据。儿科领域尚无此类数据。TDM具有成本效益，且降低剂量可能具有安全性益处。对于新型生物制剂维多珠单抗和乌司奴单抗，TDM在成人中的应用数据有限，但早期结果表明其效用同样前景广阔。在临床实践中，儿科IBD中TDM的应用正在增加，在对抗TNF治疗反应丧失的儿童中显示出与成人相似的疗效。需要在儿童中进行更多前瞻性研究，以检验TDM的前瞻性监测及与新型生物制剂的效用。
