Original article
Alimentary tract
Risk of New or Recurrent Cancer in Patients With Inflammatory Bowel Disease and Previous Cancer Exposed to Immunosuppressive and Anti-Tumor Necrosis Factor Agents

https://doi.org/10.1016/j.cgh.2015.07.037Get rights and content

Background & Aims

Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer.

Methods

We performed a retrospective analysis of data from 333 patients with IBD treated at 8 academic medical centers who developed cancer and subsequently received treatment with anti–tumor necrosis factor (TNF), anti-TNF with an antimetabolite (thiopurines, methotrexate), antimetabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated by using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared by using the log-rank test.

Results

During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible because of the relatively small sample sizes. There was no difference in time to incident cancer (P = .14) or type of incident cancer (P = .61) among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF, 0.32; 95% confidence interval [CI], 0.09–1.09; HR for anti-TNF with an antimetabolite, 0.64; 95% CI, 0.26–1.59; HR for an antimetabolite, 1.08; 95% CI, 0.54–2.15) or time to subsequent cancer between study arms (P = .22).

Conclusion

On the basis of a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an antimetabolite after cancer was not associated with an increased risk of incident cancer, compared with patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.

Section snippets

Methods

After Institutional Review Board approval at each participating site, electronic medical records from 7 academic medical centers affiliated with the newly established New York Crohn’s and Colitis Organization and Massachusetts General Hospital were identified on the basis of a diagnosis of IBD and cancer. The data obtained from each site’s electronic medical record included patients drawn from a variety of geographically separate clinical sites (major hospital, outpatient clinical centers,

Results

A total of 333 patients met inclusion criteria. Fifty-five patients were exposed to anti-TNF-α monotherapy after a diagnosis of cancer, 51 were exposed to combination therapy with anti-TNF-α and an antimetabolite (35 to thiopurine, 16 to methotrexate), 78 were exposed to antimetabolite monotherapy (71 to thiopurine, 7 to methotrexate), and 149 were not exposed to immunosuppression after a diagnosis of cancer (controls). There were some differences in baseline characteristics between IBD

Discussion

In this cohort of patients with IBD and a history of cancer, exposure to immunosuppression after a diagnosis of cancer was not associated with an increased risk of either new or recurrent cancer. To our knowledge, this is the largest study evaluating this particular subset of IBD patients. Our findings suggest that monotherapy with an anti-TNF-α or anti-metabolite agent or the combination may be as safe in IBD patients with a history of malignancy as in those who are not exposed to

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    Conflicts of interest These authors disclose the following: Jean-Frederic Colombel has received compensation from AbbVie, ABScience, Amgen, Bristol Meyers Squibb, Celltrion, Danone, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen, Immune Pharmaceuticals, Medimmune, Merck & Co, Millenium Pharmaceuticals Inc, Neovacs, Nutrition Science Partners Ltd, Pfizer Inc, Prometheus Laboratories, Protagonist, Receptos, Sanofi, Schering Plough Corporation, Second Genome, Shire, Takeda, Teva Pharmaceuticals, Tigenix, UCB Pharma, Vertex, and Dr August Wolff GmbH & Co. Steven Itzkowitz has received compensation from Exact Sciences Corporation. The remaining authors disclose no conflicts.

    Funding Supported in part by The Chemotherapy Foundation.

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