Grover Zubin, Biron Rebecca, Carman Nicholas, Lewindon Peter
Queensland Children Medical Research Institute, Brisbane, QLD, Australia; Queensland Paediatric Gastroenterology Hepatology, Royal Children's Hospital, Brisbane, QLD, Australia.
Queensland Paediatric Gastroenterology Hepatology, Royal Children's Hospital, Brisbane, QLD, Australia.
J Crohns Colitis. 2014 Aug;8(8):739-46. doi: 10.1016/j.crohns.2013.12.017. Epub 2014 Jan 18.
A significant proportion of patients with initial response to Inflximab (IFX), subsequently lose response (LOR). Multicentre paediatric studies report LOR in 33% to 50% with 3-5year follow-up. Our retrospective study examined durability of response and predictors of LOR.
From our IBD database of 185 children with CD, 65 received IFX maintenance therapy for luminal or fistulising Crohn's disease between January, 2006 and April, 2013. 47 with luminal CD ≥1year follow-up after commencing IFX were included. We evaluated variables associated with response and describe outcomes on those remaining on IFX at four time points; before IFX, after induction, at 1year and at the last follow-up. Response was divided into sustained primary, recovered, durable (combined sustained primary and recovered) and complete LOR (discontinuation from LOR or intolerance).
Overall, 28/47 (60%) children sustained primary response over a median duration of 2.83years (1.6-4.4, IQR). 19/47 (40%) developed LOR (including 2 intolerant) at a median of 11months (9-19, IQR). Of 17 with LOR, 7 were successfully re-induced giving durable response (35/47, 74%); 6 failed dose intensification needing surgery (n=2), second anti-TNF (n=2) or both (n=2). 4 had surgery without dose intensification. LOR was associated with low BMI at diagnosis, lower height Z scores prior to induction, elevated CRP following induction (p=0.007) and failure to use concomitant IM (p=0.02).
The cumulative probability of durable response to IFX in luminal CD was 83%, 74% and 70% after 1, 2, and 3years on IFX maintenance therapy.
相当一部分对英夫利昔单抗（IFX）初始有反应的患者随后会失去反应（LOR）。多中心儿科研究报告称，在3至5年的随访中，LOR发生率为33%至50%。我们的回顾性研究考察了反应的持久性以及LOR的预测因素。
从我们185例克罗恩病患儿的炎症性肠病数据库中，选取2006年1月至2013年4月期间因肠腔型或瘘管型克罗恩病接受IFX维持治疗的65例患儿。纳入47例在开始IFX治疗后有≥1年肠腔型克罗恩病随访的患儿。我们评估了与反应相关的变量，并描述了在四个时间点仍接受IFX治疗的患儿的结局；IFX治疗前、诱导治疗后、1年时和最后一次随访时。反应分为持续的初始反应、恢复、持久反应（持续的初始反应和恢复反应合并）和完全LOR（因LOR或不耐受而停药）。
总体而言，28/47（60%）例患儿维持初始反应，中位持续时间为2.83年（1.6 - 4.4，四分位间距）。19/47（40%）例患儿出现LOR（包括2例不耐受），中位时间为11个月（9 - 19，四分位间距）。在17例出现LOR的患儿中，7例成功再次诱导获得持久反应（35/47，74%）；6例剂量强化失败，需要手术（n = 2）、使用第二种抗TNF药物（n = 2）或两者都用（n = 2）。4例未进行剂量强化就接受了手术。LOR与诊断时低体重指数、诱导治疗前较低的身高Z评分、诱导治疗后升高的CRP（p = 0.007）以及未使用同时期免疫调节剂（p = 0.02）有关。
在接受IFX维持治疗1、2和3年后，肠腔型克罗恩病对IFX持久反应的累积概率分别为83%、74%和70%。
