Previous Cancer and/or Lymphoma in Patients with Refractory IBD - Con: Anti-TNF or Conventional Immunosuppressive Treatment

Abstract

Patients with IBD and prior cancer are at increased risk of developing recurrent or de novo cancer. Depending on the type of malignancy, risk factors include IBD itself, age, environmental factors, genetic susceptibility and exposure to immunosuppressants (IMS), namely thiopurines, methotrexate and anti-TNFα biologics. The procarcinogenic effect of IMS depends on the type of drug and length of exposure. Thiopurines increase the rates of nonmelanoma skin cancer and lymphomas. Methotrexate is less harmful, but data are scarce. Evidence favoring the ‘safety' of anti-TNF monotherapy is weak because most patients have been exposed to combinations of IMS prior to the development of malignancy. Anti-TNFα biologics may promote tumor proliferation and increase the risk of melanomas. Exclusion of these patients from trials with biologics, physician concerns or fear of incident cancers and medicolegal consequences, and patient concerns have led to a paucity of data regarding IMS treatment of patients with a prior malignancy. In the absence of guidelines, IMS should be avoided especially during the first 2 years after commencing cancer therapy. Depending on disease type, location and severity, 5-ASA, antibiotics, enteric nutrition, steroids alone or in combinations, seton placement, and ‘curative' or ‘diverting' surgery may allow for a crucial drug-holiday period before readministration of IMS. Preventive measures include smoking cessation, UV solar protection, annual skin examination and Pap test. If unavoidable, methotrexate should be the drug of first choice followed by anti-TNFα and then thiopurines. Patients should be managed on a case-by-case basis by a multidisciplinary team of experts.

CD73 promotes colitis‑associated tumorigenesis in mice

“…Compared with the model group, qPCR demonstrated that the levels of inflammatory cytokines, including TNF-α and IL-6, were significantly increased in the NECA group; however, there were no significant differences in the decreased expression levels of TNF-α and IL-6 between the APCP and model groups. TNF-α is a pro-inflammatory cytokine secreted by Th17 cells in IBD and IBD-associated cancer (45,46). In addition, IL-6 is one of the most important pro-inflammatory cytokines mainly produced by myeloid cells and was identified as a key promoter of carcinogenesis (47).…”

Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis

“…There is heterogeneity in natural history of IBD with varying risks of recurrence of disease-related symptoms after therapy cessation. Comprehensive models that can predict this outcome may be helpful in identifying those at highest risk for IBD relapse, and consequently most likely to require early re-initiation of immunosuppressive therapy for IBD after the index cancer diagnosis 29, 30, 66 . While many existing guidelines recommend avoiding immunosuppression for 5 years after index cancer 24–29 , our data may provide reassurance that there is no increased risk.…”

Patient considerations in the management of ulcerative colitis – role of vedolizumab

“…Malignancy was reported in only one of 297 (0.3%) patients treated with placebo (squamous cell carcinoma). 7 While expert consensus recommends avoiding anti-TNF exposure for 5 years after treatment of a malignancy, 21 it is not yet clear if vedolizumab should abide by the same rule of thumb.…”