Division of Gastroenterology, Hepatology & Nutrition, Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
SickKids Inflammatory Bowel Disease Centre, SickKids Hospital, Toronto, ON, Canada.
J Crohns Colitis. 2019 Aug 14;13(8):982-989. doi: 10.1093/ecco-jcc/jjz019.
Infliximab pharmacokinetics in steroid-refractory [SR] ulcerative colitis [UC] suggest a need for higher dosing, but data concerning efficacy of intensification in this setting are lacking in children and inconsistent overall.
Paediatric patients [N = 125] treated with infliximab for SR or steroid-dependent UC were retrospectively reviewed. Outcomes [clinical response and remission, colectomy, mucosal healing, safety] with standard vs intensified induction [mean induction dose ≥7 mg/kg or interval ≤5 weeks between doses 1 and 3] were compared.
Among 125 patients [median age 14 years, median UC duration 0.7 years, 74 SR], 73 [58%] received standard induction and 52 [42%] received intensified induction. Overall, 73 [58%] achieved remission (judged by physician global assessment [PGA] and paediatric UC activity index [PUCAI]≤10]. Among patients in remission, 7 [10%] experienced secondary loss of response by a median of 0.7 [IQR 0.4-1.0] years. Of the 74 SR patients, 17 [23%] underwent colectomy, and of the 51 steroid-dependent patients, 12 [24%] underwent colectomy. Intensified induction in SR patients was associated with a higher chance of remission (hazard ratio [HR] 3.2, p = 0.02) and a lower chance of colectomy [HR 0.4, p = 0.05], but did not improve outcomes in steroid-dependent patients. During follow-up, 46/73 [63%] patients in remission had regimen individualization, with similar rates of return to standard dosing after 1 year between those with initial intensified or standard induction. Follow-up endoscopy, performed in 35/73 patients in remission, demonstrated mucosal healing for 66%. Adverse events were rare, despite use of intensified regimens.
These data suggest a benefit from intensified infliximab induction specifically among children with steroid-refractory UC. Prospective studies comparing dosing regimens and incorporating therapeutic drug monitoring should be undertaken.
英夫利昔单抗在类固醇难治性 [SR] 溃疡性结肠炎 [UC] 中的药代动力学表明需要更高的剂量，但在儿童中缺乏关于强化治疗效果的数据，且总体上不一致。
回顾性分析了 125 例接受英夫利昔单抗治疗 SR 或类固醇依赖性 UC 的儿科患者。比较了标准诱导与强化诱导 [平均诱导剂量≥7mg/kg 或剂量 1 和 3 之间的间隔≤5 周] 的疗效[临床缓解和缓解率、结肠切除术、黏膜愈合、安全性]。
在 125 例患者中[中位年龄 14 岁，中位 UC 病程 0.7 年，74 例 SR]，73 例[58%]接受标准诱导，52 例[42%]接受强化诱导。总体而言，73 例[58%]达到缓解（根据医生总体评估 [PGA] 和儿科 UC 活动指数 [PUCAI]≤10 评估）。在缓解的患者中，7 例[10%]在中位数为 0.7 [IQR 0.4-1.0] 年内出现继发性缓解丧失。在 74 例 SR 患者中，17 例[23%]接受了结肠切除术，在 51 例类固醇依赖性患者中，12 例[24%]接受了结肠切除术。SR 患者强化诱导与更高的缓解几率相关（危险比 [HR] 3.2，p=0.02）和更低的结肠切除术几率相关[HR 0.4，p=0.05]，但在类固醇依赖性患者中并未改善结局。在随访期间，73 例缓解患者中有 46 例[63%]进行了方案个体化，在初始强化或标准诱导的患者中，1 年后恢复标准剂量的比例相似。在 73 例缓解患者中有 35 例进行了随访内镜检查，显示 66%的患者黏膜愈合。尽管使用了强化方案，但不良反应罕见。
这些数据表明，强化英夫利昔单抗诱导治疗在类固醇难治性 UC 儿童中具有益处。应开展比较剂量方案并纳入治疗药物监测的前瞻性研究。
