The Annual AIBD Meeting was just held in early December. AIBD is the preeminent conference for the clinical care of patients with inflammatory bowel disease (IBD). I spoke on the risks and management of cancer in patients with IBD.
IBD, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract driven by inappropriate immune responses to an altered gut microbiome in genetically susceptible individuals. Patients with IBD are at an increased risk of developing intestinal neoplasia—particularly colorectal neoplasia ([CRN], colorectal dysplasia and colorectal cancer [CRC])—as a consequence of chronic colonic inflammation. Others include small bowel adenocarcinoma, intestinal lymphoma, and anal cancer. In addition to cancers common in the general population, patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies, thought to be a consequence of immunosuppressive therapies and an underlying inflammatory state, including cholangiocarcinoma, skin cancer, hematologic malignancies, genitourinary cancer, and cervical cancer.
With an aging population, the medical management of patients with IBD and active or recent cancer will become increasingly more important. The effect of cancer treatment on underlying IBD disease activity and the risk of cancer progression or recurrence with IBD-directed immunosuppressive therapy are unique concerns in this patient population. Exploratory data has suggested that cytotoxic chemotherapy for cancer may have a protective effect on intestinal inflammation. Conversely, hormonal therapy may be associated with an increased risk of IBD flare. While further evidence is needed to clarify the impact of hormonal therapy on the development and disease course of IBD, patients diagnosed with cancers that are commonly treated with hormone deprivation therapy may be at increased risk for IBD disease reactivation and should be closely followed by a gastroenterologist. In patients with underlying IBD, treatment with immune checkpoint inhibitors may also increase the risk of relapse in IBD and need for biologic therapy.
While there is considerable evidence for the risks of malignancy associated with immunosuppressive therapy in patients with IBD, less is known regarding the risk in those with active cancer. Randomized control trials and long-term safety registries have little to no data on IBD patients with active cancer, and smaller observational studies have commonly excluded patients with active cancer. Recently, a retrospective, multi-center study evaluating the safety of IBD-directed immunosuppressive therapy in patients with active and recent prior cancer, found similar rates of cancer progression in patients exposed to TNF⍺ antagonists vs. non-TNF biologics vs. immunomodulator monotherapy.
IBD patients with a history of cancer may be at risk for developing a new or recurrent cancer. Evidence based recommendations for the management of IBD-directed immunosuppressive therapy in patients with prior cancer remains limited. Given the known risks of lymphoma and other malignancies associated with immunosuppression, there may be concern that IBD-directed therapy increases the risk of cancer recurrence. However, retrospective data has not corroborated this increased risk. In a multi-center center study from the New York Crohn’s and Colitis Organization (NYCCO), exposure to TNFα antagonists, immunomodulators, or combination therapy was not associated with an increased risk of incident cancer, new or recurrence, compared to those not receiving immunosuppression. Prospective studies on the risks of immunosuppressive therapy will be highly informative when managing patients with IBD and cancer. The ongoing SAPPHIRE registry (Safety of immunosuppression in a prospective cohort of inflammatory bowel disease patients with a history of cancer) is currently examining the risks of cancer recurrence in IBD patients exposed to immunosuppression compared to those not exposed to immunosuppression. In preliminary data, exposure to biologics or immunomodulators was not associated with an increased risk of new or recurrent cancer when compared to no therapy.
Much remains unknown regarding the interaction between IBD, medical therapy for IBD, cancer development, cancer treatment, and the risk of cancer recurrence in patients with IBD and a history of cancer. Overall, data is lacking regarding specific cancers, treatments, and risk of recurrence under varying medications for IBD. More data from prospective registries such as SAPPHIRE will permit the development of evidence-based, quantitative risk-benefit models including cancer and IBD-related variables to assist clinicians in managing this complex patient population.
AIBD 2022 highlighted critically important topics for providers managing complex patients with IBD.
Dr. Axelrad has no conflicts of interest to report.
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