Murias Sara, Magallares Lorena, Albizuri Fatima, Pascual-Salcedo Dora, Dreesen Erwin, Mulleman Denis
Departments of *Pediatric Rheumatology,†Pediatric Gastroenterology,‡Pediatric Dermatology, and§Immunology, University Hospital La Paz, Madrid, Spain;¶Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; and‖Department of Rheumatology, Université François-Rabelais de Tours, Tours, France.
Ther Drug Monit. 2017 Aug;39(4):370-378. doi: 10.1097/FTD.0000000000000423.
Biopharmaceuticals have recently emerged as effective treatments for refractory pediatric autoimmune conditions. Several reports have shown a relationship between drug concentration, antidrug antibodies, and clinical response in these patients, strongly suggesting the potential interest, usefulness, and reliability of therapeutic drug monitoring (TDM) in children. This article reviews the current state of research in juvenile idiopathic arthritis, pediatric inflammatory bowel disease, and pediatric psoriasis from a TDM point of view. There is a remarkable lack of evidence-based data in pediatric patients, which is reflected throughout the article. Most investigations of TDM are focused on research of tumor necrosis factor alpha antagonists in inflammatory bowel disease, albeit preliminary publications are emerging from pediatric rheumatologists and dermatologists. To date, immunogenicity has been a primary concern, particularly regarding infliximab and adalimumab therapy in children, as it may lead to a loss of therapeutic response. Preliminary investigations show that adjusting the dose according to blood drug concentrations improves disease outcomes by overcoming antidrug antibodies, suggesting a crucial role for TDM. Patients who receive other drugs, such as etanercept, abatacept, or tocilizumab, could benefit from TDM because dosage can be optimized by adjusting it to the minimum effective dose.
生物制药最近已成为治疗难治性儿童自身免疫性疾病的有效方法。一些报告显示了这些患者的药物浓度、抗药抗体和临床反应之间的关系,有力地表明了治疗药物监测(TDM)在儿童中的潜在价值、实用性和可靠性。本文从TDM的角度综述了青少年特发性关节炎、儿童炎症性肠病和儿童银屑病的研究现状。儿科患者明显缺乏循证数据,这在整篇文章中都有所体现。大多数TDM研究集中在炎症性肠病中肿瘤坏死因子α拮抗剂的研究,尽管儿科风湿病学家和皮肤科医生也有初步的相关发表。迄今为止,免疫原性一直是主要关注点,特别是在儿童英夫利昔单抗和阿达木单抗治疗方面,因为这可能导致治疗反应丧失。初步研究表明,根据血药浓度调整剂量可通过克服抗药抗体改善疾病结局,这表明TDM起着关键作用。接受其他药物(如依那西普、阿巴西普或托珠单抗)治疗的患者也可从TDM中获益,因为可以通过将剂量调整至最低有效剂量来实现优化。