AUTHOR=Li Li , Chen Rirong , Zhang Yingfan , Zhou Gaoshi , Chen Baili , Zeng Zhirong , Chen Minhu , Zhang Shenghong 

TITLE=A Novel Model Based on Serum Biomarkers to Predict Primary Non-Response to Infliximab in Crohn’s Disease

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.646673

DOI=10.3389/fimmu.2021.646673

ISSN=1664-3224

ABSTRACT=Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.