Comparable Immune Function Inhibition by the Infliximab Biosimilar CT-P13: Implications for Treatment of Inflammatory Bowel Disease.

Abstract

BACKGROUND AND AIMS:

CT-P13 is the first biosimilar monoclonal antibody to infliximab, and was recently approved in the European Union, Japan, Korea, and USA for all six indications of infliximab. However, studies directly assessing the biologic activity of CT-P13 versus inflximab in the context of inflammatory bowel disease [IBD] are still scanty. In the present study, we aimed to compare the biological activities of CT-P13 and infliximab with specific focus on intestinal cells so as to gain insight into the potential biosimilarity of these two agents for treatment of IBD.

METHODS:

CT-P13 and infliximab were investigated and compared by in vitro experiments for their neutralisation ability of soluble tumour necrosis factor alpha [sTNFα] and membrane-bound tumour necrosis factor alpha [mTNFα], suppression of cytokine release by reverse signalling, induction of regulatory macrophages and wound healing, and antibody-dependent cell cytotoxicity [ADCC].

RESULTS:

CT-P13 showed similar biological activities to infliximab as gauged by neutralisation of soluble TNFα, as well as blockade of apoptosis and suppression of pro-inflammatory cytokines in intestinal Caco-2 cells. Infliximab and CT-P13 equally induced apoptosis and outside-to-inside signals through transmembrane TNFα [tmTNFα]. Moreover, regulatory macrophage induction and ensuing wound healing were similarly exerted by CT-P13 and infliximab. However, neither CT-P13 nor infliximab exerted any significant ADCC of ex vivo-stimulated peripheral blood monocytes or lamina propria mononuclear cells from IBD patients.

CONCLUSIONS:

These findings indicate that CT-P13 and infliximab exert highly similar biological activities in intestinal cells, and further support a mechanistic comparability of these two drugs in the treatment of IBD.

• Authors: Ki Jung Lim, So Jung Lee, Sunghwan Kim, Su Yeon Lee, Min Seob Lee, Yoon A Park, Eun Jin Choi, Eun Beom Lee, Hwang Keun Jun, Jong Moon Cho, SooYoung Lee, Ki Sung Kwon, Byung Pil Lim, Myung-Shin Jeon, Eui Cheol Shin, Yong Sung Choi, Ella Fudim, Orit Picard, Miri Yavzori, Shomron Ben-Horin, Shin Jae Chang
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 11 Issue 5 Pg. 593-602 (May 01 2017) ISSN: 1876-4479 [Electronic] England
• PMID: 28453766 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]

Chemical References

• Antibodies, Monoclonal
• Biosimilar Pharmaceuticals
• CT-P13
• Cytokines
• Gastrointestinal Agents
• Tumor Necrosis Factor-alpha
• Infliximab

Topics

• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Biosimilar Pharmaceuticals (pharmacology, therapeutic use)
• Caco-2 Cells (drug effects)
• Cytokines (metabolism)
• Gastrointestinal Agents (pharmacology, therapeutic use)
• Humans
• In Vitro Techniques
• Inflammatory Bowel Diseases (drug therapy)
• Infliximab (pharmacology, therapeutic use)
• Intestines (cytology, drug effects, immunology)
• Macrophages (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)
• Wound Healing (drug effects)