Harzallah Ines, Rigaill Josselin, Williet Nicolas, Paul Stephane, Roblin Xavier
Laboratoire d'Immunologie et d'Immunomonitoring, CIC1408, GIMAPEA3064, CHU de Saint-Etienne, France.
Department of Gastroenterology, Service de Gastrologie-Enterologie-Hepatologie, CHU de Saint-Etienne, France.
Therap Adv Gastroenterol. 2017 Jan;10(1):89-100. doi: 10.1177/1756283X16676194. Epub 2016 Nov 15.
Golimumab (GLM) is the latest anti-tumor necrosis factor (TNF) that gained its marketing license. Thanks to the PURSUIT induction and maintenance trials, it was approved for the treatment of ulcerative colitis (UC) in 2013. The other anti-TNF drugs available are infliximab and adalimumab. These two drugs have validated algorithms concerning prescription and therapeutic drug monitoring (TDM) but little is known about GLM. The available data on GLM's exposure-response relationship in UC are from the PURSUIT trials and are recently published. The data reveal all the factors that may impact the pharmacokinetic (PK) parameters: dosage, body weight (BW), concomitant drugs, the presence of anti-drug antibodies (ADAbs), sex and age. In addition, the GLM trough level at steady-state appears to be correlated with the patient's improvement which may make it a precious indicator to predict the clinical response. There is, however, no consensus on a possible therapeutic level or cutoff associated with clinical response, remission, or any other outcome measure such as endoscopic healing in UC. This lack of a threshold value, and its validation with different assay techniques, makes it difficult to use GLM TDM in clinical practice. As with other anti-TNF agents, GLM is associated with development of ADAbs, of which the prevalence and effects are still insufficiently described. The objective of this review is to describe current data and understanding of the PK of GLM including serum concentrations of GLM and ADAbs in UC patients. Better understanding of these parameters could lead to improved patient care with GLM.
戈利木单抗（GLM）是最新获得上市许可的抗肿瘤坏死因子（TNF）药物。得益于“PURSUIT诱导和维持试验”，它于2013年被批准用于治疗溃疡性结肠炎（UC）。其他可用的抗TNF药物有英夫利昔单抗和阿达木单抗。这两种药物有关于处方和治疗药物监测（TDM）的有效算法，但关于GLM的了解却很少。关于GLM在UC中的暴露-反应关系的现有数据来自“PURSUIT试验”且最近已发表。这些数据揭示了所有可能影响药代动力学（PK）参数的因素：剂量、体重（BW）、合并用药、抗药抗体（ADAbs）的存在、性别和年龄。此外，稳态时的GLM谷浓度似乎与患者的病情改善相关，这可能使其成为预测临床反应的宝贵指标。然而，对于与临床反应、缓解或任何其他结局指标（如UC中的内镜愈合）相关的可能治疗水平或临界值尚无共识。缺乏阈值以及用不同检测技术对其进行验证，使得在临床实践中使用GLM TDM变得困难。与其他抗TNF药物一样，GLM与ADAbs的产生有关，其发生率和影响仍描述不足。本综述的目的是描述关于GLM药代动力学的当前数据和认识，包括UC患者中GLM和ADAbs的血清浓度。更好地了解这些参数可能会改善GLM对患者的治疗效果。
