Development of a C1q-immobilized (Cim) assay to measure total antibodies to infliximab and its clinical relevance in patients with inflammatory bowel disease.

Authors:
Naoki Yoshimura
Naoki Yoshimura
University of Pittsburgh School of Medicine
United States
Yoko Yokoyama
Yoko Yokoyama
Hyogo College of Medicine
Japan
Minako Sako
Minako Sako
Social Insurance Central General Hospital
Japan
Nobuo Aoyama
Nobuo Aoyama
Kobe University School of Medicine
Kobe | Japan
Fumihito Hirai
Fumihito Hirai
Fukuoka University Chikushi Hospital
Koji Sawada
Koji Sawada
Hyogo College of Medicine
Japan
Nobuhito Kashiwagi
Nobuhito Kashiwagi
Kyoto Prefectural University of Medicine
Yasuo Suzuki
Yasuo Suzuki
Tokai University School of Medicine
Japan

Cytokine 2019 Aug 16;120:54-61. Epub 2019 Apr 16.

IBD Centre, Toho University Sakura Medical Centre, Chiba, Japan. Electronic address:

Objective: Determination of antibodies to infliximab (ATI) is desirable for the management of patients with inflammatory bowel disease (IBD) who receive infliximab. Conventional ligand-binding ATI-assays detect only free-form of ATI, potentially increasing the proportion of patients with undetectable ATI, but with adequate trough infliximab (TRI) level who experience loss of response (LOR) to infliximab. We investigated this assertion using a novel ATI-Cim assay.

Methods: An ATI-Cim assay was developed by utilizing a C1q-immobilized plate, detecting free-form and ATI-infliximab complexes. Plasma ATI in 137 consecutive IBD patients, 56 with sustained clinical response (SCR), 76 with LOR and 5 with infusion reactions was measured.

Results: ATI levels reached a plateau following addition of up to 25 μg/mL infliximab to different concentrations of free-form ATI. ATI concentration did not significantly change during infliximab infusion (P = 0.4316). ATI concentration > 0.153 μg/mL was associated with LOR (odds ratio 3.0: 95%, confidence interval 1.5 to 6.1, P = 0.0029). The number of patients with undetectable ATI was higher in SCR than in LOR, 53.6% vs 22.4% (P = 0.0004). Patients with SCR and LOR were divided into 4 subgroups by combined cut-off ATI and TRI values. (A) ATI > 0.153 μg/mL and TRI ≤ 2 μg/mL; (B) ATI > 0.153 μg/mL and TRI > 2 μg/mL; (C) ATI ≤ 0.153 μg/mL and TRI ≤ 2 μg/mL; (D) ATI ≤ 0.153 μg/mL and TRI > 2 μg/mL. The frequency of LOR showed a decreasing trend from subgroup A to D, 80.8%, 64.1%, 55.2% and 36.8%, respectively (P = 0.0003).

Conclusions: The measured ATI level appeared to define the patients' response to infliximab. Combining ATI and trough infliximab levels should help to understand the mechanism of LOR and make therapeutic algorithms.

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Source
http://dx.doi.org/10.1016/j.cyto.2019.02.014DOI Listing
August 2019

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