Engström Johanna, Lönnkvist Maria, Befrits Ragnar, Ljung Tryggve, Diaz-Tartera Hetzel, Holst Mikael, Hellström Per M
Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University , Uppsala , Sweden.
Department of Medicine, Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institutet , Stockholm , Sweden.
Scand J Gastroenterol. 2019 Sep;54(9):1081-1088. doi: 10.1080/00365521.2019.1660402. Epub 2019 Sep 9.
Fecal calprotectin (FC) and serum C-reactive protein (CRP) are biomarkers of disease activity in Crohn's disease (CD) and ulcerative colitis (UC). We assessed FC, CRP, Harvey-Bradshaw index (HBi), partial Mayo Clinic Scoring (pMCS) and a cytokine panel during infliximab induction to predict therapy outcome. FC, CRP and clinical indices were evaluated in 123 (76 CD, 47 UC) patients before infliximab induction and after 12 weeks. Responders were monitored 48 weeks for an 'incident' (dosage increase, shortened dosage interval, surgery). Cutoff values for FC and CRP were obtained using receiver-operating characteristics (ROC). Disease progression was analyzed with Kaplan-Meier survivals, log-rank test and logistic regression for combined biomarkers. Cytokines were analyzed with Luminex multiplexing system. Following infliximab, FC and CRP declined ( < .0001) along with HBi for CD and pMCS for UC. Simultaneously, IL-6 and TNF-α decreased, while IL-10 increased. Optimal FC ROC cutoff was 221 µg/g (sensitivity 66%, specificity 67%, AUC 0.71) and CRP ROC cutoff 2.1 mg/L (sensitivity 54%, specificity 60%, AUC 0.58). In CD, FC > 221 µg/g ( < .0001), but not CRP > 2.1 mg/L predicted an 'incident'. However, combined FC and CRP also predicted an 'incident' ( < .042). In UC, both FC > 221 µg/g ( < .0005) and CRP > 2.1 mg/L ( = .0334) predicted 'incident', as did combined biomarkers ( < .005). Clinical disease activity is reduced by treatment with infliximab. In CD, persistently high FC, but not CRP, predict a treatment 'incident', whereas in UC both high FC and high CRP predict 'incident'. Combined FC and CRP values also predict an 'incident'.
粪便钙卫蛋白（FC）和血清C反应蛋白（CRP）是克罗恩病（CD）和溃疡性结肠炎（UC）疾病活动的生物标志物。我们在英夫利昔单抗诱导治疗期间评估了FC、CRP、哈维-布拉德肖指数（HBi）、梅奥诊所部分评分（pMCS）以及一组细胞因子，以预测治疗结果。在123例（76例CD、47例UC）患者中，在英夫利昔单抗诱导治疗前和12周后评估了FC、CRP和临床指标。对缓解者进行了48周的监测，观察是否出现“事件”（剂量增加、缩短给药间隔、手术）。使用受试者工作特征（ROC）曲线获得FC和CRP的临界值。采用Kaplan-Meier生存曲线、对数秩检验和联合生物标志物的逻辑回归分析疾病进展情况。使用Luminex多重检测系统分析细胞因子。英夫利昔单抗治疗后，FC和CRP下降（<0.0001），CD患者的HBi和UC患者的pMCS也下降。同时，白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）减少，而白细胞介素-10（IL-10）增加。FC的最佳ROC临界值为221μg/g（敏感性66%，特异性67%，曲线下面积[AUC]0.71），CRP的ROC临界值为2.1mg/L（敏感性54%，特异性60%，AUC 0.58）。在CD中，FC>221μg/g（<0.0001）可预测“事件”发生，而CRP>2.1mg/L则不能。然而，联合FC和CRP也可预测“事件”发生（<0.042）。在UC中，FC>221μg/g（<0.0005）和CRP>2.1mg/L（=0.0334）均可预测“事件”发生，联合生物标志物也有此预测作用（<0.005）。英夫利昔单抗治疗可降低临床疾病活动度。在CD中，持续高FC水平而非高CRP水平可预测治疗“事件”发生，而在UC中，高FC和高CRP水平均可预测“事件”发生。联合FC和CRP值也可预测“事件”发生。
