Treatment for IBD Increases Risk of Malignant Lymphoproliferative Disorders
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Treatment for IBD Increases Risk of Malignant Lymphoproliferative Disorders

NEW YORK -- October 19, 2009 -- Patients with Crohn’s disease or ulcerative colitis regularly receive treatment with thiopurine drugs to maintain remission. However, according to a study published online first and in an upcoming edition of The Lancet, this treatment increases the risk of malignant lymphoproliferative disorders (LD).

To date, no excess risk of LD has been shown in patients with irritable bowel disease (IBD), but data involving patients given thiopurines have been conflicting. In view of the increasing numbers of IBD patients using thiopurines, Laurent Beaugerie, Hôpital Saint-Antoine, Paris, France, and colleagues decided the possible increased risk for these patients must be investigated.

The observational cohort study analysed 19,486 patients with IBD, of whom 60% had Crohn’s disease and 40% had ulcerative colitis or unclassified IBD. All were enrolled in a nationwide French cohort by 680 gastroenterologists, who 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 35 months.

At baseline, 30% of patients were receiving, 14% had discontinued, and 56% had never received thiopurines. A total of 23 new cases of LD were diagnosed, consisting of 1 case of Hodgkin’s lymphoma and 22 cases of non-Hodgkin lymphoma.

The incidence rates of LD were 0.90 per 1000 patient-years in those receiving, 0.20/1000 patient-years in those who had discontinued, and 0.26/1000 patient-years in those who had never received thiopurines (P = .0054).

Statistical analysis showed that patients receiving thiopurines had a more than a 5-fold increased risk of LD compared with those who had never received the drugs. Most cases associated with thiopurine exposure were similar to those seen in post-transplant disease. Old age, male sex, and longer duration of IBD were also associated with increased risk of LD.

“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,” the authors concluded. “For elderly patients and unlimited treatment periods, the question should be addressed in dedicated studies.”

In an accompanying comment, Geert D’Haens, MD, Imelda GI Clinical Research Centre, Bonheiden, Belgium and University Hospital Gasthuisberg, Leuven, Belgium and Paul Rutgeerts, MD, University Hospital Gasthuisberg, said: “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.”

SOURCE: The Lancet

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