Inflammatory Bowel Diseases

Skip Navigation LinksHome > May 2013 - Volume 19 - Issue 6 > The Cytotoxic Effects of Certolizumab Pegol and Golimumab Me...
Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318280b169
Original Basic Science Article

The Cytotoxic Effects of Certolizumab Pegol and Golimumab Mediated by Transmembrane Tumor Necrosis Factor α

Ueda, Naoyasu MD*; Tsukamoto, Hiroshi MD, PhD*; Mitoma, Hiroki MD, PhD†,‡; Ayano, Masahiro MD*; Tanaka, Atsushi MD*; Ohta, Shun-ichiro MD*; Inoue, Yasushi MD, PhD*; Arinobu, Yojiro MD, PhD§; Niiro, Hiroaki MD, PhD*; Akashi, Koichi MD, PhD*; Horiuchi, Takahiko MD, PhD*

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Background: Anti–tumor necrosis factor α (anti-TNF-α) agents have been successfully applied for the treatment of rheumatoid arthritis, Crohn's disease, and other chronic inflammatory diseases. Not only the neutralization of soluble TNF-α but also the effect on transmembrane TNF-α is important mechanisms of action of anti-TNF-α agents. This study investigated the cytotoxic effects of new anti-TNF-α agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-α.

Methods: Transmembrane TNF-α–expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF-α agent to transmembrane TNF-α, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined.

Results: Certolizumab pegol and golimumab bound to transmembrane TNF-α. Golimumab induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNF-α–expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab.

Conclusions: The cytotoxic effects of anti-TNF-α agents on TNF-α–expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNF-α–producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.

© Crohn's & Colitis Foundation of America, Inc.

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