Berends Sophie E, Strik Anne S, Jansen Jeroen M, de Boer Nanne K, van Egmond Pleun S, Brandse Johannan F, Mathôt Ron A, D'Haens Geert R, Löwenberg Mark
Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam , Amsterdam , Netherlands.
Hospital Pharmacy, Amsterdam UMC, University of Amsterdam , Amsterdam , Netherlands.
Scand J Gastroenterol. 2019 Jun;54(6):700-706. doi: 10.1080/00365521.2019.1619828. Epub 2019 May 27.
Golimumab (GLM) is approved for the treatment of moderate to severe ulcerative colitis (UC). Higher serum concentrations of anti-tumor necrosis factor (TNF) agents are associated with improved clinical and endoscopic outcomes. Correlations between GLM serum concentrations and clinical and endoscopic outcomes were investigated during induction and maintenance treatment. In addition, a population pharmacokinetic model was developed to identify factors associated with the pharmacokinetics of GLM in UC. A prospective observational trial (GO-KINETIC) was conducted in patients with moderate to severe UC receiving induction and maintenance treatment with GLM. Clinical and endoscopic outcomes were evaluated, fecal GLM concentrations were measured and pharmacokinetic data were analyzed. A total of 20 patients were enrolled. At week 8 (after induction treatment), 12 out of 20 patients (60%) showed an endoscopic response (≥1 point reduction in endoscopic Mayo score). Patients with endoscopic response at week 8 had numerically higher median GLM serum concentrations at week 2 compared to endoscopic non-responders: 9.1 µg/ml [5.9-12.3] 7.1 µg/mL [5.2-9.0]; = .384, respectively. At week 52, 3/20 patients (15%) achieved endoscopic remission (endoscopic Mayo score ≤1) and continued GLM treatment. Population pharmacokinetic analysis showed an inverse association between albumin concentrations and GLM clearance. GLM concentrations were undetectable in fecal samples. After induction therapy, 60% of the patients showed endoscopic response. During maintenance therapy, about one third of patients discontinued GLM treatment because of loss of response. These patients might benefit from dose optimization.
戈利木单抗（GLM）已获批用于治疗中度至重度溃疡性结肠炎（UC）。抗肿瘤坏死因子（TNF）药物的血清浓度越高，临床和内镜检查结果改善越明显。在诱导治疗和维持治疗期间，研究了GLM血清浓度与临床和内镜检查结果之间的相关性。此外，还建立了群体药代动力学模型，以确定与UC中GLM药代动力学相关的因素。对接受GLM诱导治疗和维持治疗的中度至重度UC患者进行了一项前瞻性观察试验（GO-KINETIC）。评估了临床和内镜检查结果，测量了粪便GLM浓度并分析了药代动力学数据。共招募了20名患者。在第8周（诱导治疗后），20名患者中有12名（60%）显示出内镜反应（内镜梅奥评分降低≥1分）。与内镜无反应者相比，第8周有内镜反应的患者在第2周的GLM血清浓度中位数在数值上更高：分别为9.1µg/ml[5.9-12.3]和7.1µg/mL[5.2-9.0]；P=0.384）。在第52周，20名患者中有3名（15%）实现了内镜缓解（内镜梅奥评分≤1）并继续接受GLM治疗。群体药代动力学分析显示白蛋白浓度与GLM清除率呈负相关。在粪便样本中未检测到GLM浓度。诱导治疗后，60%的患者显示出内镜反应。在维持治疗期间，约三分之一的患者因反应丧失而停止GLM治疗。这些患者可能从剂量优化中获益。
