Tumor Necrosis Factor-Alpha Inhibitors and Risks of Malignancy

Abstract

Tumor necrosis factor (TNF)-alpha has been established in the innate and acquired immune response in various disease processes, including both Crohn’s disease (CD) and ulcerative colitis (UC). This has led to the development and widespread use of anti-TNF therapies for the management of inflammatory bowel diseases (IBD). Infection, malignancy, antibody development, and infusion reactions are some of the major adverse reactions associated with anti-TNF agents. This review summarizes the evidence, including the limitations of the currently available literature, on various types of malignancy that have been associated with IBD therapies, with a focus upon anti-TNF agents. We highlight the association of anti-TNF agents with melanoma, while thiopurines in combination with anti-TNF agents are more strongly associated with non-melanoma skin cancer (NMSC). Additionally, we discuss the compounded risk of anti-TNFs with immunomodulators in the development of lymphoma and, in particular, the risk of hepatosplenic T-cell lymphoma (HSTCL) in younger patients. We also summarize the limited data on risks of solid tumors and cervical cancer associated with anti-TNF agents. In contrast, we highlight the established reduction in colorectal cancer risk with the use of immunosuppressive agents in IBD that treat inflammatory activity. Finally, we provide recommendations on how to discuss the risks and benefits of anti-TNF agents with patients, emphasizing methods of preventing complications of immunosuppressive medications in IBD. A shared decision-making process in selection of therapies, with appropriate follow-up, monitoring, and continued discussions of risks and benefits, will allow us to effectively and safely treat our patients with IBD.