PMID- 34367126
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20210927
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - A Novel Model Based on Serum Biomarkers to Predict Primary Non-Response to 
      Infliximab in Crohn's Disease.
PG  - 646673
LID - 10.3389/fimmu.2021.646673 [doi]
LID - 646673
AB  - 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.
CI  - Copyright (c) 2021 Li, Chen, Zhang, Zhou, Chen, Zeng, Chen and Zhang.
FAU - Li, Li
AU  - Li L
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Chen, Rirong
AU  - Chen R
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zhang, Yingfan
AU  - Zhang Y
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zhou, Gaoshi
AU  - Zhou G
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Chen, Baili
AU  - Chen B
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zeng, Zhirong
AU  - Zeng Z
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Chen, Minhu
AU  - Chen M
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zhang, Shenghong
AU  - Zhang S
AD  - Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210722
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Gastrointestinal Agents)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - B72HH48FLU (Infliximab)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Biomarkers/*blood
MH  - C-Reactive Protein/*metabolism
MH  - Chemokine CCL2/*blood
MH  - Cohort Studies
MH  - Crohn Disease/blood/diagnosis/*drug therapy
MH  - Cytokines/blood
MH  - Female
MH  - Gastrointestinal Agents/therapeutic use
MH  - Humans
MH  - Infliximab/*therapeutic use
MH  - Logistic Models
MH  - Male
MH  - Matrix Metalloproteinase 3/*blood
MH  - Models, Biological
MH  - Predictive Value of Tests
MH  - ROC Curve
MH  - Young Adult
PMC - PMC8339550
OTO - NOTNLM
OT  - Crohn's disease
OT  - infliximab
OT  - prediction
OT  - primary non-response
OT  - serum biomarkers
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/10 06:00
MHDA- 2021/09/28 06:00
PMCR- 2021/01/01
CRDT- 2021/08/09 06:30
PHST- 2020/12/27 00:00 [received]
PHST- 2021/07/07 00:00 [accepted]
PHST- 2021/08/09 06:30 [entrez]
PHST- 2021/08/10 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.646673 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jul 22;12:646673. doi: 10.3389/fimmu.2021.646673. eCollection 
      2021.