*Division of Gastroenterology, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut;†Janssen Research & Development, LLC, Springhouse, Pennsylvania;‡The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel;§IBD Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada;‖Pediatric Gastroenterology and Nutrition, University Hospital Brussels, Free University Brussels, Bruxelles, Belgium;¶Department of Pediatrics, University of California, San Francisco, California;**Pediatric Gastroenterology, Clinical Development and Research Affairs, Goryeb Children's Hospital/Atlantic Health, Morristown, New Jersey; and††Department of Pediatrics, Division of Gastroenterology, Seattle Children's Hospital, University of Washington, Seattle, Washington.
Inflamm Bowel Dis. 2017 Dec;23(12):2227-2237. doi: 10.1097/MIB.0000000000001262.
Current treatments for pediatric ulcerative colitis (UC) are limited. We evaluated the pharmacokinetics and clinical benefits of subcutaneous golimumab, an anti-tumor necrosis factor agent, in moderately-to-severely active pediatric patients with UC refractory to conventional therapy.
We report a multicenter, open-label study of golimumab with a pharmacokinetics phase (week 0-14). Patients had moderately-to-severely active UC and were naive to anti-tumor necrosis factor treatment. At weeks 0 and 2, patients received golimumab induction dosed by weight (<45 kg [90/45 mg/m]; ≥45 kg [200/100 mg]). Week 6 clinical responders continued golimumab q4w. Serum golimumab concentrations, clinical outcomes (Mayo score, PUCAI score), and adverse events are reported.
Thirty-five patients (71.4% pancolitis) aged 6 to 17 years had baseline median (interquartile range), age, weight, and disease duration of 15.0 (11.0-16.0) years, 50.6 (35.2-59.0) kg, and 1.2 (0.6-3.1) years, respectively. Baseline Mayo and PUCAI scores were 8.0 (6.0-9.0) and 45 (35.0-65.0), respectively. Median (interquartile range) serum golimumab concentrations were comparable to a historical reference adult UC population at weeks 2 (5.72 [3.80-9.17] μg/mL), 4 (7.61 [3.22-9.51] μg/mL), and 6 (2.64 [0.92-3.83] μg/mL). Serum golimumab concentrations were generally lower in the <45 kg than ≥45 kg weight subgroup. At week 6, 60%, 34%, and 54%, of patients achieved Mayo clinical response, PUCAI clinical remission, and mucosal healing (Mayo subscore 0/1). No clinically important safety concerns were reported.
This open-label study demonstrates that pediatric and adult golimumab pharmacokinetics are similar. Clinical benefit and safety shows promise in biologically naive pediatric patients with UC.
目前治疗儿童溃疡性结肠炎（UC）的方法有限。我们评估了皮下注射戈利木单抗（一种抗肿瘤坏死因子药物）在对常规治疗无效的中重度活动期儿童 UC 患者中的药代动力学和临床获益。
我们报告了一项多中心、开放性戈利木单抗研究，包括药代动力学阶段（第 0-14 周）。患者患有中重度活动期 UC，且以前未接受过抗肿瘤坏死因子治疗。在第 0 周和第 2 周，患者根据体重接受戈利木单抗诱导剂量（<45 kg [90/45 mg/m]；≥45 kg [200/100 mg]）。第 6 周临床应答者继续接受 q4w 戈利木单抗治疗。报告血清戈利木单抗浓度、临床结局（Mayo 评分、PUCAI 评分）和不良事件。
35 名年龄在 6 至 17 岁的患者（71.4%全结肠炎）的基线中位数（四分位距）为 15.0（11.0-16.0）岁、50.6（35.2-59.0）kg 和 1.2（0.6-3.1）年。基线 Mayo 和 PUCAI 评分分别为 8.0（6.0-9.0）和 45（35.0-65.0）。第 2 周（5.72[3.80-9.17]μg/mL）、第 4 周（7.61[3.22-9.51]μg/mL）和第 6 周（2.64[0.92-3.83]μg/mL）的血清戈利木单抗浓度中位数与历史参考成人 UC 人群相似。在第 6 周，60%、34%和 54%的患者达到 Mayo 临床应答、PUCAI 临床缓解和黏膜愈合（Mayo 亚评分 0/1）。未报告有临床意义的安全性问题。
这项开放性研究表明，儿科和成人戈利木单抗的药代动力学相似。在生物学上无治疗经验的儿童 UC 患者中，临床获益和安全性有一定前景。
