Dupont-Lucas Claire, Sternszus Robert, Ezri Jessica, Leibovitch Samantha, Gervais France, Amre Devendra, Deslandres Colette
Department of Paediatric Gastroenterology, Hepatology and Nutrition, Sainte Justine Hospital, Montreal, QC, Canada Research Centre, Sainte Justine Hospital, Montreal, QC, Canada.
Department of Paediatric Gastroenterology, Hepatology and Nutrition, Sainte Justine Hospital, Montreal, QC, Canada.
J Crohns Colitis. 2016 Jul;10(7):795-804. doi: 10.1093/ecco-jcc/jjw038. Epub 2016 Jan 28.
Loss of response to infliximab resulting in discontinuation of therapy is a frequent problem encountered in paediatric Crohn's disease. Although identifying patients at risk of failure could have important implications for follow-up, literature in this area remains sparse. Our primary aim was to identify predictors of loss of response to infliximab among patients who were responders to induction. The secondary aim was to identify predictors of non-response to induction.
A retrospective cohort of patients with paediatric Crohn's disease treated with infliximab between 2000 and 2013 was followed until loss of response to infliximab or transfer to adult care. Predictors of response to induction therapy were studied by multivariate logistic regression. Time to treatment failure was analysed with a multivariate Cox model.
Two-hundred and forty-eight patients were eligible for the study. Of these, 196 (79%) were responders to induction (57% clinical remission and 22% clinical response) and 52 (21%) were non-responders. Steroid resistance was the only variable independently associated with primary non-response (odds ratio [OR] 4.57, 95% confidence interval [CI] 1.67-12.50, p = 0.002). Thirty-one of the 196 responders discontinued infliximab due to loss of response after a mean of 1.6±1.3 years of treatment. Predictors of loss of response were level of response to induction (clinical response vs clinical remission, hazard ratio [HR] 3.74, 95% CI 1.80-7.80, p = 0.0004) and isolated colonic disease (HR 2.72, 95% CI 1.30-5.71, p = 0.008).
Patients who fail to achieve clinical remission after induction and/or who have isolated colonic disease are at increased risk of loss of response to infliximab.
对英夫利昔单抗治疗反应丧失导致治疗中断是儿童克罗恩病中常见的问题。尽管识别有治疗失败风险的患者对随访具有重要意义,但该领域的文献仍然稀少。我们的主要目的是在诱导治疗有反应的患者中识别对英夫利昔单抗反应丧失的预测因素。次要目的是识别诱导治疗无反应的预测因素。
对2000年至2013年间接受英夫利昔单抗治疗的儿童克罗恩病患者进行回顾性队列研究,随访至对英夫利昔单抗反应丧失或转至成人护理。通过多因素逻辑回归研究诱导治疗反应的预测因素。用多因素Cox模型分析治疗失败时间。
248例患者符合研究条件。其中,196例(79%)诱导治疗有反应(57%临床缓解,22%临床反应),52例(21%)无反应。激素抵抗是唯一与初始无反应独立相关的变量(比值比[OR]4.57,95%置信区间[CI]1.67 - 12.50,p = 0.002)。196例有反应者中有31例在平均1.6±1.3年的治疗后因反应丧失而停用英夫利昔单抗。反应丧失的预测因素是诱导治疗的反应水平(临床反应与临床缓解,风险比[HR]3.74,95%CI 1.80 - 7.80,p = 0.0004)和孤立性结肠疾病(HR 2.72,95%CI 1.30 - 5.71,p = 0.008)。
诱导治疗后未实现临床缓解和/或患有孤立性结肠疾病的患者对英夫利昔单抗反应丧失的风险增加。