Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2022; 28(23): 2582-2596
Published online Jun 21, 2022. doi: 10.3748/wjg.v28.i23.2582
Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn’s disease under infliximab therapy
Wan-Ting Cao, Rong Huang, Shan Liu, Yi-Hong Fan, Mao-Sheng Xu, Yi Xu, Hui Ni
Wan-Ting Cao, Rong Huang, Yi-Hong Fan, Yi Xu, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
Shan Liu, Department of Clinical Evaluation Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
Mao-Sheng Xu, Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
Hui Ni, Department of Nursing, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
Author contributions: Fan YH designed the research; Cao WT performed the research; Cao WT and Liu S analyzed the data; Cao WT, Huang R, Ni H and Xu MS wrote the paper; Xu Y supervised the paper; All authors have read and approve the final manuscript.
Supported by National Natural Science Foundation of China, No. 81473506 and No. 81971600; Zhejiang TCM Science and Technology Project, No. 2019ZA056, No. 2021ZA057 and No. 2016ZA077.
Institutional review board statement: This study was reviewed and approved by the ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, No. 2021-KL-024-02.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: Some or all data, models, or code generated or used during the study are available from the corresponding author by request. People could contact the corresponding author to get the data which is not used for commercial purposes.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi-Hong Fan, MD, Associate Professor, Chief Doctor, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, No. 54 Youdian Road, Shangcheng District, Hangzhou 310006, Zhejiang Province, China. yhfansjr@163.com
Received: October 30, 2021
Peer-review started: October 30, 2021
First decision: March 11, 2022
Revised: March 25, 2022
Accepted: May 7, 2022
Article in press: May 7, 2022
Published online: June 21, 2022
Processing time: 229 Days and 3.9 Hours
Abstract
BACKGROUND

Infliximab trough level (ITL) severely affects therapeutic outcomes of Crohn’s disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas.

AIM

To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.

METHODS

CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn’s disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn’s disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.

RESULTS

At week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 μg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 μg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 μg/mL in combination with FCP > 238 μg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 μg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 μg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 μg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 μg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 μg/mL (92.68% vs 30.77%).

CONCLUSION

Combination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Keywords: Infliximab trough level; C-reactive protein; Fecal calprotectin; Crohn’s disease; Clinical remission; Long-term endoscopic outcomes

Core Tip: Previous investigations, contraposing Crohn’s disease patients under infliximab (IFX) maintenance therapy, have indicated that higher IFX trough levels (ITLs) were associated with sustained drug response and clinical remission in inflammatory bowel disease patients, while lower ITLs were linked to secondary unresponsiveness of IFX. Currently, endoscopic remission or mucosal healing has been considered the main goal of biological therapy. Our study manifested that Crohn’s disease patients with higher levels of IFX blood concentration and lower levels of inflammatory biomarkers tended to have a better long-term endoscopic prognosis. Combining ITL, fecal calprotectin and C-reactive protein monitoring was helpful for the timely adjustment of IFX treatment strategy.