Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer

Beaugerie, Laurent; Carrat, Fabrice; Colombel, Jean–Frédéric; Bouvier, Anne–Marie; Sokol, Harry; Babouri, Abdenour; Carbonnel, Franck; Laharie, David; Faucheron, Jean‐Luc; Simon, Tabassome; Gramont, Aimery de; Peyrin–Biroulet, Laurent

doi:10.1136/gutjnl-2013-305763

Cited by 130 publications

(107 citation statements)

References 18 publications

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“…The first data came from Beaugerie et al [12], who reported on the effect of IMS treatment in a cohort of 405 patients with a prior cancer who were included in the CESAME study. Of these patients, 260 had been diagnosed with a cancer more than 2 years prior to enrollment and 145 within 2 years of enrollment in the study.…”

Section: Are Ibd Patients With a Previous Malignancy At Risk Of Develmentioning

confidence: 99%

“…Recent reports have also associated thiopurines with an increased risk of all-cause malignancies in IBD [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26]. Incorporation of 6-TGN nucleotides in the DNA and RNA is responsible for induction of both remission of disease and mutagenesis and cancer promotion.…”

Section: What Are the Potential Carcinogenic Properties Of Ims Used Imentioning

confidence: 99%

“…However, IMS do promote cancer, which depends on the type of IMS and the length of treatment. This effect is mediated via direct and indirect procarcinogenic mechanisms, the most important being the induction of alterations in DNA synthesis and/or DNA mismatch repair leading to malignant transformation of cells and impairment of immune surveillance of cells carrying latent infections by oncogenic viruses, such as the human papilloma viruses or the Epstein-Barr virus (EBV) [9,10,11,12,13]. Clinically, this may be associated with several scenarios: development of new cancers, growth and clinical expression of currently silent malignancies, expansion and metastasis of localized cancers, and recurrence of cancers which were thought to have been previously cured or controlled by treatment [11,12,13,14,15].…”

Section: Can Ims Cause or Provoke Cancer In Ibd Patients?mentioning

confidence: 99%

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

Mantzaris¹

2014

Dig Dis

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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.

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Section: Are Ibd Patients With a Previous Malignancy At Risk Of Develmentioning

confidence: 99%

Section: What Are the Potential Carcinogenic Properties Of Ims Used Imentioning

confidence: 99%

Section: Can Ims Cause or Provoke Cancer In Ibd Patients?mentioning

confidence: 99%

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

Mantzaris¹

2014

Dig Dis

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“…In recent data from the prospective French CESAME cohort, the overall incidence of cancer was significantly higher in patients with previous cancer when compared with patients without a history of cancer, with a multivariate-adjusted hazard ratio of 1.9 (95% CI: 1.2-3.0, p = 0.003) [15]. Importantly, among patients with a prior history of malignancy, there was no significant difference in the actuarial probability of remaining free of cancer recurrence or new cancer according to exposure to any immunomodulator at cohort entry.…”

Section: Cancer Risk In Patients With Previous Cancermentioning

confidence: 99%

“…It could be difficult in some situations, such as occurrence of ipsilateral subsequent breast cancer, to differentiate cancer recurrence from development of a new tumor [15]. …”

Section: Cancer Risk In Patients With Previous Cancermentioning

confidence: 99%

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

Laharie¹

2014

Dig Dis

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Management of patients with IBD and a past or current malignancy has become more frequent in daily practice. As trends in IBD therapy are moving to more immunomodulators, administered earlier and for longer periods than ever, an increasing number of IBD patients with a prior malignancy may receive conventional immunosuppressants (IS) and/or anti-TNF. However, few data are available for managing this IBD subpopulation due to three main reasons: (1) previous cancer is usually an exclusion criterion from all clinical trials, (2) guidelines do not recommend any immunomodulator use in patients who have had a malignancy within the last 5 years, and (3) physicians are reluctant to use immunomodulators which could reactivate dormant micrometastasis. However, there is a lack of scientific evidence for avoiding immunomodulators in IBD patients with previous cancer. In a recently published cohort of patients with previous cancer, no excess incidence of incident cancer was associated with exposure to IS. Data with anti-TNF are lacking in IBD. Recently in a registry including 79 patients with refractory IBD who started an anti-TNF therapy while having had a prior malignancy within the past 5 years, survival rates without incident cancer were 96 and 72% at 1 and 5 years, respectively. Thus, evidence to not start IS and/or anti-TNF therapy in IBD patients who have had a previous cancer is weak. Pending larger studies, a case-by-case joint decision taken with the oncologist and the patient is recommended, and should take IBD and the cancer risk-benefit ratio for using immunomodulators to treat refractory disease into consideration.

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Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer

et al. 2016

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Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer

Abstract: Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk.

Cited by 130 publications

References 18 publications

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

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

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

Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer

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