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A.S. Cheifetz, J.D. Feuerstein (eds.), Treatment of Inflammatory
Bowel Disease with Biologics, https://doi.org/10.1007/978-3-319-60276-9_3
Chapter 3
Antitumor Necrosis Factor Agents
in Crohn’s Disease
Byron P. Vaughn
Introduction
Antitumor necrosis factor (anti-TNF) agents revolutionized the treatment for Crohn’s
disease (CD). As discussed in the previous chapter, TNF is a key role in stimulating
pro-inflammatory cytokines as well as the expression of adhesion molecules and
fibroblast proliferation [ 1 , 2 ]. Clinically, elevated fecal TNF concentrations correlate
with disease activity, while inhibition of TNF prevents granuloma formation in vitro
[ 3 – 5 ]. These associations led to the hypothesis that inhibiting TNF could be a thera-
peutic intervention in inflammatory diseases mediated by TNF. Developed at
New York University, a murine monoclonal antibody (cA2) was constructed with a
high affinity and specificity for human TNF [ 6 ]. This antibody eventually became
infliximab (Remicade, Janssen) and was initially approved for Crohn’s disease in
- Since that time, other anti-TNFs have been approved for the treatment of
Crohn’s disease including adalimumab (Humira, AbbVie) in 2007 and certolizumab
pegol (Cimzia, UCB) in 2008. This chapter will review in detail each approved anti-
TNF for Crohn’s disease highlighting key efficacy data from major clinical trials.
Infliximab
Infliximab (IFX) is a chimeric, mouse-human monoclonal antibody against human-
soluble and transmembrane-bound TNF [ 7 ]. The constant region of the antibody is
human, while the variable regions are murine (approximately 25%). Clinical use of
IFX was first described in a 12-year-old girl who failed therapy with prednisone,
B.P. Vaughn
Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota,
410 Delaware Street SE, MMC36, Minneapolis, MN 55455, USA
e-mail: [email protected]