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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_13
Chapter 13
Tumor Necrosis Factor-Alpha Inhibitors
and Risks of Malignancy
Julia T. Hughes and Millie D. Long
Introduction
Tumor necrosis factor (TNF)-alpha plays a role in both the innate and acquired
immune response. Furthermore, elevated levels of TNF-alpha have been demon-
strated in various immune-mediated disease processes, including inflammatory
bowel disease (IBD) [ 1 ]. TNF-alpha has been shown to act as a key pro-
inflammatory mediator in Crohn’s disease (CD), a discovery that prompted the
development and utilization of anti-TNFs for the management of CD in the 1990s
[ 2 ]. Anti-TNFs reduce hypercoagulability and inhibit granuloma formation, which
make them useful therapeutic tools in CD [ 3 , 4 ]. The inhibition of granuloma for-
mation also decreases the ability to clear mycobacterium and other intracellular
organisms [ 5 , 6 ], which raises concerns about immunologic compromise, particu-
larly in the domains of infection and malignancy.
Infection, malignancy, antibody development, and infusion reactions are
some of the major adverse reactions associated with anti-TNFs. While infec-
tious complications are well recognized with anti-TNF therapy, particularly
due to their relatively higher frequency of occurrence over shorter time periods
of therapy, complications of malignancy are not as readily observed or docu-
J.T. Hughes (*) • M.D. Long
Division of Gastroenterology and Hepatology, Department of Medicine, University of North
Carolina at Chapel Hill, Campus Box 7080, Chapel Hill, NC 27599-7080, USA
Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill,
Campus Box 7080, Chapel Hill, NC 27599-7080, USA
e-mail: [email protected]