Inflammatory Bowel Disease (IBD): Treatment Increases The Risk Of Infection-Related Cancers

Editor's Choice
Main Category: Irritable-Bowel Syndrome
Also Included In: Cancer / Oncology
Article Date: 19 Oct 2009 - 0:00 PDT

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Ulcerative colitis or Crohn's disease is generally referred to as inflammatory bowel disease (IBD). Patients regularly receive treatment with thiopurine drugs to sustain remission. An article published Online First and in a future edition of The Lancet shows that this treatment increases the risk of malignant lymphoproliferative disorders (LD). Those are cancers associated with viral infection, particularly those linked to Epstein-Barr virus (EBV) infection. The article is the work of Professor Laurent Beaugerie, Hôpital Saint-Antoine, Paris, France, and colleagues.

The thiopurine azathioprine and its metabolite, 6-mercaptopurine, have immunosuppressive properties and maintain remission in IBD. Organ transplant recipients receiving these drugs as part of their immunosuppressive therapy are at an increased risk of developing LD, especially via infection by EBV. Up to now, no excess risk of LD has been exposed in patients with IBD. However, data concerning patients given thiopurines have been contradictory. Since the number of IBD patients using thiopurines is rising, the authors judged necessary to investigate the possible increased risk for these patients.

A total of 19,486 patients with inflammatory bowel disease were analysed in this observational cohort study. Around 60 percent of them had Crohn's disease and 40 percent had ulcerative colitis or unclassified inflammatory bowel disease. All were enrolled in a nationwide French cohort by 680 gastroenterologists. The doctors reported details of immunosuppressive therapy during the observation period, cases of cancer (LD), and deaths. The risk of LD was assessed according to thiopurine exposure. Median follow-up was thirty-five months.

At baseline, 30 percent of patients were receiving, 14 percent had discontinued, and 56 percent had never received thiopurines. There was diagnosis of 23 new cases of LD, including one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoma. The incidence rates of LD were 0.90 per 1,000 patient-years in those receiving, 0.20 per 1,000 patient-years in those who had discontinued, and 0.26 per 1,000 patient-years in those who had never received thiopurines (p=0•0054). Statistical analysis showed that patients receiving thiopurines had a more-than-five-fold increased risk of LD compared with those who had never received the drugs. Most cases linked with thiopurine exposure were similar to those seen in post-transplant disease. Also associated with increased risk of LD were old age, male sex, and longer duration of inflammatory bowel disease.

The authors write in conclusion: "Extrapolating our results, the absolute cumulative risk of lymphoproliferative disorder in young patients receiving a 10-year course of thiopurines remains low (<1%) and does not undermine the positive risk-benefit ratio of these drugs. For elderly patients and unlimited treatment periods, the question should be addressed in dedicated studies."

In an associated comment, Dr Geert D'Haens, Imelda GI Clinical Research Centre, Bonheiden, Belgium and University Hospital Gasthuisberg, Leuven, Belgium and Dr Paul Rutgeerts University Hospital Gasthuisberg, Leuven, Belgium, remark: "Although we recognise the slightly increased risk of lymphoma, these agents will probably remain one of the cornerstones of treatment. Nonetheless, physicians should be cautious when prolonged combined and deep immunosuppression is needed to achieve disease control."

"Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study"
Laurent Beaugerie, Nicole Brousse, Anne Marie Bouvier, Jean Frédéric Colombel, Marc Lémann, Jacques Cosnes, Xavier Hébuterne, Antoine Cortot, Yoram Bouhnik, Jean Pierre Gendre, Tabassome Simon, Marc Maynadié, Olivier Hermine, Jean Faivre, Fabrice Carrat, for the CESAME Study Group
DOI: 10.1016/S0140-6736(09)61302-7
The Lancet

Written by Stephanie Brunner (B.A.)
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