New or Recurrent Cancer in Patients With IBD
New or Recurrent Cancer in Patients With IBD
Objective. To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants.
Design. Among the 17,047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer.
Results. The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer.
Conclusions. 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.
IBDs are lifelong diseases that primarily affect young patients. Sustained mucosal healing is becoming the standard objective of the long-term treatment of IBD. This objective can be achieved currently by maintenance treatment with immunosuppressants, including thiopurines, methotrexate and anti-tumor necrosis factor (TNF) agents. Unfortunately, there is no major trend towards the spontaneous extinction of IBD activity with time, and disease activity often recurs after withdrawal of immunosuppressants. Collectively, these factors lead to an extensive and prolonged use of immunosuppressants in patients with IBD.
De novo cancers and cancer recurrence may be promoted by immunosuppressants, due to various mechanisms that include decreased immunosurveillance, facilitated action of oncogenic viruses and direct alteration of DNA. These mechanisms differ considerably between immunosuppressants and cancer subtypes.
In the post-transplant setting, prolonged use of immunosuppressants, including thiopurines and calcineurin inhibitors, is associated with an increased risk of de novo cancers. Cancer recurrence is also promoted by immunosuppressants. The excess risk of cancer recurrence depends primarily on the cancer subtype and on the time between completion of cancer treatment and the initiation of immunosuppressive therapy.
In the general population, patients with a personal history of cancer have an overall small excess risk of developing a second cancer in addition to the risk of cancer recurrence. The risk of developing a second cancer is more pronounced in individuals who have experienced the first cancer during childhood or adolescence. In chronic inflammatory diseases, there are few data on cancer risk in patients with a history of cancer who were either exposed or not exposed to immunosuppressants. The data from two cohorts of patients with rheumatoid arthritis and a history of cancer suggested that the risk of new or recurrent cancer was not significantly different between patients treated with the combination of anti-TNF and methotrexate and patients treated with methotrexate alone.
The risk of new or recurrent cancer under immunosuppressants in patients with IBD with a history of cancer is unknown. We addressed this question in the CESAME (Cancers Et Surrisque Associé aux Maladies inflammatoires intestinales En France) French nationwide observational cohort. This cohort was assembled in the early 2000s to assess the risks of any cancer or high-grade dysplasia in patients with IBD and to determine the impact of immunosuppressant use on these risks. In the present study, we identified patients who had been diagnosed with cancer prior to entry into the cohort. We calculated the incidence rates of any cancer in patients with or without previous cancer. Through a multivariate analysis, we assessed the independent roles of cancer history and immunosuppressant use on the risk of incident cancer. We then assessed, through survival analysis and a nested case-control study, the impact of immunosuppressants on the risk of new or recurrent cancer in patients with previous cancer.
Abstract and Introduction
Abstract
Objective. To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants.
Design. Among the 17,047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer.
Results. The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer.
Conclusions. 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.
Introduction
IBDs are lifelong diseases that primarily affect young patients. Sustained mucosal healing is becoming the standard objective of the long-term treatment of IBD. This objective can be achieved currently by maintenance treatment with immunosuppressants, including thiopurines, methotrexate and anti-tumor necrosis factor (TNF) agents. Unfortunately, there is no major trend towards the spontaneous extinction of IBD activity with time, and disease activity often recurs after withdrawal of immunosuppressants. Collectively, these factors lead to an extensive and prolonged use of immunosuppressants in patients with IBD.
De novo cancers and cancer recurrence may be promoted by immunosuppressants, due to various mechanisms that include decreased immunosurveillance, facilitated action of oncogenic viruses and direct alteration of DNA. These mechanisms differ considerably between immunosuppressants and cancer subtypes.
In the post-transplant setting, prolonged use of immunosuppressants, including thiopurines and calcineurin inhibitors, is associated with an increased risk of de novo cancers. Cancer recurrence is also promoted by immunosuppressants. The excess risk of cancer recurrence depends primarily on the cancer subtype and on the time between completion of cancer treatment and the initiation of immunosuppressive therapy.
In the general population, patients with a personal history of cancer have an overall small excess risk of developing a second cancer in addition to the risk of cancer recurrence. The risk of developing a second cancer is more pronounced in individuals who have experienced the first cancer during childhood or adolescence. In chronic inflammatory diseases, there are few data on cancer risk in patients with a history of cancer who were either exposed or not exposed to immunosuppressants. The data from two cohorts of patients with rheumatoid arthritis and a history of cancer suggested that the risk of new or recurrent cancer was not significantly different between patients treated with the combination of anti-TNF and methotrexate and patients treated with methotrexate alone.
The risk of new or recurrent cancer under immunosuppressants in patients with IBD with a history of cancer is unknown. We addressed this question in the CESAME (Cancers Et Surrisque Associé aux Maladies inflammatoires intestinales En France) French nationwide observational cohort. This cohort was assembled in the early 2000s to assess the risks of any cancer or high-grade dysplasia in patients with IBD and to determine the impact of immunosuppressant use on these risks. In the present study, we identified patients who had been diagnosed with cancer prior to entry into the cohort. We calculated the incidence rates of any cancer in patients with or without previous cancer. Through a multivariate analysis, we assessed the independent roles of cancer history and immunosuppressant use on the risk of incident cancer. We then assessed, through survival analysis and a nested case-control study, the impact of immunosuppressants on the risk of new or recurrent cancer in patients with previous cancer.
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