225anti-TNF agents. Such examinations are recommended in posttransplant popula-
tions where risk is also higher. Finally, tertiary prevention refers to treatment of
IBD to prevent complications of the disease itself, such as development of abscess
or requirement for surgery. By optimizing IBD therapy early in disease course,
we may be able to prevent late complications associated with untreated inflamma-
tion over time.
Limitations in the Literature and Queries for Future
Investigations
While there has been increasing interest and investigation into anti-TNF agents
and their associated clinical benefits and risks, including malignancy, data are
limited overall. Studies are often retrospective or use administrative data sources
which are limited by the risk of misclassification and lack of clinical detail. Long-
term cancer risks will need to be assessed as anti-TNF use increases over time,
preferably in a prospective fashion. Additionally, the use of novel combinations of
medications, such as vedolizumab (anti-integrin therapy) or ustekinumab (anti-
p40 IL 12/23 inhibitor) and thiopurines, compared to anti-TNF-containing regi-
mens, will need to be further studied. We also need better detail on combinations
of therapy, including methotrexate as an immunomodulator combined with anti-
TNF agents. Additionally, the use of anti-TNF agents in patients with a history of
prior malignancy is an area that warrants further investigation to help to guide
evidence-based treatment recommendations in this group. We anticipate a growing
body of literature regarding biologic therapies and malignancy in the coming
years, which will help guide both clinicians and patients in selecting therapies to
manage IBD.
Summary
Over the past two decades, increasing rates of anti-TNF use in IBD populations
have dramatically changed the therapeutic landscape. These agents have allowed
patients to reach steroid-free remission and have often allowed for mucosal healing.
However, these agents also come with a series of risks, which must be communi-
cated effectively with patients. Risk communication of absolute numbers with com-
mon denominators is imperative in order for patients to effectively interpret risk.
Importantly, population-based studies have shown that while GI malignancy rates in
IBD populations have decreased with more effective therapies and/or improved sur-
veillance techniques, there has not been a concomitant increase in hematologic or
other extraintestinal malignancies [ 7 ]. This demonstrates that the risk/benefit ratio
13 Tumor Necrosis Factor-Alpha Inhibitors and Risks of Malignancy