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mented in the literature. This is likely due to the lower frequency and more
insidious development over time of malignant complications.
This review will summarize the evidence, including the limitations of the cur-
rently available literature, on various types of malignancy that have been associated
with IBD therapies, with a focus upon anti-TNF agents. Additionally, although risks
of certain malignancies exist, one must also consider the benefits of using these
agents for the treatment of moderate to severe IBD. An approach to discussing the
risks and benefits of anti-TNFs with patients will be provided. Finally, we will also
emphasize those preventable malignant complications and provide recommenda-
tions for three forms of prevention in IBD as they relate to malignancy: primary,
secondary, and tertiary prevention.
Risk of Malignancy with Anti-TNFs in IBD
Anti-TNFs have been available for the treatment of CD in the late 1990s and subse-
quently for ulcerative colitis (UC) in the 2000s. These agents have demonstrated
overall safety and efficacy in IBD management. However, concerns have arisen about
potential associations with cancers such as non-melanoma skin cancer (NMSC), mel-
anoma, lymphoproliferative and myeloproliferative disorders, hepatosplenic T-cell
lymphoma, and other solid tumors. When assessing the risks of anti- TNF therapy, it
is also critical to consider the roles of concomitant immunomodulators and cortico-
steroid therapy that are often used in conjunction with or prior to these medications.
In a population-based cohort in Denmark spanning over 30 years, investigators
compared the risks of gastrointestinal (GI) and extraintestinal cancers in IBD
patients over time periods prior to and after widespread use of anti-TNF agents for
the treatment of IBD. CD was associated with GI malignancies (SIR, 1.2; 95% CI,
1.0–1.4) and extraintestinal malignancies (SIR, 1.3; 95% CI, 1.2–1.4), with a stron-
ger association for hematologic malignancies (SIR, 1.9; 95% CI, 1.5–2.3), smoking-
related malignancies (SIR, 1.5; 95% CI, 1.3–1.8), and melanoma (SIR, 1.4; 95% CI,
1.0–1.9). UC was more weakly associated with GI and extraintestinal malignancies
(SIR, 1.1; 95% CI, 1.0–1.2; and SIR, 1.1; 95% CI, 1.0–1.1, respectively). Importantly,
the risk of gastrointestinal cancers decreased since 1978, without an increase in the
risk of extraintestinal cancers over time (Fig. 13.1). This demonstrates that effective
treatment of inflammation in the GI tract and/or appropriate surveillance and man-
agement of dysplasia may be contributing to an overall reduction in the risk of GI
malignancies. Notably, anti-TNF therapies are not concomitantly increasing the
overall rate of extraintestinal malignancies in patients with IBD [ 7 ].
J.T. Hughes and M.D. Long