Ohem Jan, Hradsky Ondrej, Zarubova Kristyna, Copova Ivana, Bukovska Petra, Prusa Richard, Malickova Karin, Bronsky Jiri
Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles, University and Motol University Hospital, Prague, Czech Republic.
Dig Dis. 2018;36(1):40-48. doi: 10.1159/000477962. Epub 2017 Aug 18.
In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels.
Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.
在成人中，英夫利昔单抗（IFX）水平与疾病活动度相关，而抗英夫利昔单抗抗体（ATIs）可预测治疗失败。我们旨在确定儿科人群中IFX水平和ATIs与疾病活动度之间的关联。我们前瞻性地收集了65例克罗恩病（CD）患者（年龄10.5 - 15.1岁）在使用IFX前的血液、粪便和临床数据，并测量了IFX谷浓度水平、ATIs以及粪便钙卫蛋白水平（CPT）。样本在维持治疗期间采集。我们使用多变量分析来确定IFX水平的预测因素。
较低的IFX水平与ATIs阳性相关（比值比0.027，95%置信区间0.009 - 0.077）。IFX水平较低的患者中发现较高的C反应蛋白（CRP）水平、红细胞沉降率和CPT水平。以CRP水平<5 mg/L作为实验室缓解的标志物，计算出IFX水平≥1.1 µg/mL时疾病活动度的敏感性（0.5）和特异性（0.74）的最佳组合。在以CPT≤100 µg/g作为缓解定义的模型中，最佳IFX谷浓度水平为3.5 µg/mL。在我们的研究人群中未发现缓解与ATIs之间存在独立关联。然而，我们发现IFX水平与血清白蛋白水平之间存在独立关联（比值比1.364，95%置信区间1.169 - 1.593），p < 0.001。关键信息：在IFX与ATIs以及IFX与疾病活动度之间的关联方面，儿科人群与成人人群相似。
