Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Immunol. 2021 Jul 22;12:646673. doi: 10.3389/fimmu.2021.646673. eCollection 2021.
Infliximab is effective in inducing and maintaining remission in patients with Crohn's disease (CD), but primary non-response (PNR) occurs in 10-30% of cases. We investigated whether serum biomarkers are effective in predicting PNR in patients with CD.
From January 2016 to April 2020, a total of 260 patients were recruited to this prospective and retrospective cohort study. Serum samples were collected at baseline and week 2 of infliximab treatment. Serum levels of 35 cytokines were assessed in 18 patients from the discovery cohort and were further evaluated in the 60-patient cohort 1. Then, candidate cytokines and other serological biomarkers were used to construct a predictive model by logistic regression in a 182-patient cohort 2. PNR was defined based on the change of CD activity index or clinical symptoms.
Among the 35 cytokines, matrix metalloproteinase 3(MMP3) and C-C motif ligand 2 (CCL2) were two effective serum biomarkers associated with PNR in both the discovery cohort and cohort 1. In cohort 2, serum level of MMP3, CCL2 and C-reactive protein (CRP) at 2 weeks after infliximab injection were independent predictors of PNR, with odds ratios (95% confidence interval) of 1.108(1.059-1.159), 0.940(0.920-0.965) and 1.102(1.031-1.117), respectively. A PNR classifier combining these three indicators had a large area under the curve [0.896(95% CI:0.895-0.897)] and negative predictive value [0.918(95%CI:0.917-0.919)] to predict PNR to infliximab.
MMP3, CCL2, and CRP are promising biomarkers in prediction of PNR to infliximab, and PNR classifier could accurately predict PNR and may be useful in clinical practice for therapy selection.
英夫利昔单抗在诱导和维持克罗恩病（CD）患者缓解方面有效，但约 10-30%的患者会出现原发性无应答（PNR）。我们研究了血清生物标志物是否能有效预测 CD 患者的 PNR。
从 2016 年 1 月到 2020 年 4 月，共有 260 名患者被纳入这项前瞻性和回顾性队列研究。在英夫利昔单抗治疗的基线和第 2 周采集血清样本。在发现队列的 18 名患者中评估了 35 种细胞因子的血清水平，并在第 1 队列的 60 名患者中进一步评估。然后，在第 2 队列的 182 名患者中，通过逻辑回归构建候选细胞因子和其他血清生物标志物的预测模型。PNR 根据 CD 活动指数或临床症状的变化来定义。
在 35 种细胞因子中，基质金属蛋白酶 3（MMP3）和 C 型趋化因子配体 2（CCL2）是在发现队列和第 1 队列中与 PNR 相关的两种有效的血清生物标志物。在第 2 队列中，英夫利昔单抗注射后 2 周时的 MMP3、CCL2 和 C 反应蛋白（CRP）的血清水平是 PNR 的独立预测因子，优势比（95%置信区间）分别为 1.108（1.059-1.159）、0.940（0.920-0.965）和 1.102（1.031-1.117）。将这三个指标结合起来的 PNR 分类器具有较大的曲线下面积[0.896（95%CI：0.895-0.897）]和阴性预测值[0.918（95%CI：0.917-0.919）]，以预测英夫利昔单抗的 PNR。
MMP3、CCL2 和 CRP 是预测英夫利昔单抗 PNR 的有前途的生物标志物，PNR 分类器可以准确预测 PNR，可能对临床实践中的治疗选择有用。
