克罗恩病内镜下黏膜愈合与英夫利西单抗谷浓度的相关性

Correlation between endoscopic mucosal healing and infliximab trough concentration in patients with Crohn’s disease

目的 分析克罗恩病(Crohn’s disease, CD)患者英夫利西单抗(infliximab, IFX)谷浓度与黏膜愈合的相关性,探讨达到黏膜愈合的IFX最佳谷浓度阈值。方法 回顾性分析2017年7月—2020年9月在同济大学附属第十人民医院接受IFX治疗的216例CD患者的临床资料,包括NRS2002评分、CD活动指数(Crohn’s disease activity index, CDAI)评分、免疫抑制剂使用情况、C-反应蛋白、血清白蛋白、血红蛋白等。黏膜愈合定义为:CD简化内镜评分<3分。将患者分为黏膜愈合组和黏膜未愈合组,比较两组的IFX谷浓度。统计学方法采用独立样本t检验和卡方检验。结果 黏膜愈合组(68例)血清IFX谷浓度中位数明显高于黏膜未愈合组(148例),差异有统计学意义(3.4 vs 0.7μg/mL,P<0.001)。黏膜愈合的IFX最佳谷浓度为2.25μg/mL(AUC 0.75)。在多变量Logistic回归分析中,IFX谷浓度(OR=4.45,95%CI 2.21~8.97)与黏膜愈合显著相关。此外,抗英夫利西单抗抗体(OR=1.00)与黏膜黏膜愈合的相关性较低。结论 CD患者IFX谷浓度与内镜下黏膜愈合密切关系,国内患者达到黏膜愈合所需的IFX谷浓度为2.25μg/mL低于国外水平。

Objective To analyze the correlation between the trough concentration of infliximab(IFX) and mucosal healing in patients with Crohn’s disease(CD). including NRS2002 score, CDAI score, immunosuppressant use, C-reactive protein, serum albumin, hemoglobin, et al. Methods The clinical data of 216 patients with CD who received IFX treatment at Shanghai Tenth People’s Hospital from July 2017 to September 2020 were retrospectively analyzed. Mucosal healing is defined as CD simplified endoscopy score <3 points. There were 68 patients with mucosal healing and 148 patients with mucosal non-healing, and the trough concentrations of IFX were compared between the two groups. Independent sample t test and chi-square test were used for statistical analysis. Results The median serum IFX trough concentration in the mucosal healing group was significantly higher than that in the mucosal non-healing group(3.4 vs 0.7 μg/mL, P<0.001). The optimal trough concentration of IFX for mucosal healing was 2.25 μg/mL(AUC 0.75). The multivariate logistic regression analysis showed that IFX trough concentration was significantly correlated with mucosal healing(OR=4.55,95%CI 2.21-8.97). In addition, the anti-infliximab antibody had no correlation with mucosal healing(OR=1.00,P=0.911). Conclusion The trough concentration of IFX in patients with CD is closely related to endoscopic mucosal healing. The recommended trough concentration of IFX required for mucosal healing is 2.25 μg/mL in this study.