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More on Lymphoma Risk from IBD Therapy

Immunomodulatory agents seem to be the principal culprits in raising the risk for lymphoma.

Long-term therapy with thiopurines for inflammatory bowel disease (IBD) is associated with a several-fold increased risk for non-Hodgkin lymphoma. However, data on whether tumor necrosis factor α (TNF-α) inhibitors administered alone increase lymphoma risk are mixed. In the current study, investigators conducted a retrospective database review to analyze the risks for T-cell non-Hodgkin lymphoma in patients receiving TNF-α inhibitors, thiopurines, or both.

Investigators identified 91 cases of T-cell non-Hodgkin lymphoma in patients treated with TNF-α inhibitors from the FDA Adverse Event Reporting System between 2003 and 2010 and 9 additional cases from the Medline database. Of these 100 patients, 38 had rheumatoid arthritis, 36 had Crohn disease, 9 had ulcerative colitis, 11 had psoriasis, and 6 had ankylosing spondylitis. Sixty-eight percent of patients were also treated with an immunomodulator.

Concomitant use of TNF-α inhibitors and thiopurines or use of thiopurines alone was associated with an increased risk for T-cell non-Hodgkin lymphoma, but use of TNF-α inhibitors alone was not associated with an increased risk for T-cell non-Hodgkin lymphoma. The most common histologic subtypes were hepatosplenic T-cell lymphoma and mycosis fungoides/Sezary syndrome, accounting for 30% and 20% of cases, respectively, and occurring more frequently than in the general population.

Comment: These data support the conclusion that the increased risk for lymphoma from inflammatory bowel disease therapy is principally attributable to immunomodulatory agents, particularly 6-mercaptopurine and azathioprine. Use of tumor necrosis factor α inhibitors alone seems safe, which has been found in other studies. However, many patients with IBD seem to benefit from combination therapy, which can reduce the loss of response associated with development of antibodies to TNF-α inhibitors. This tradeoff will remain an ongoing conundrum for patients with IBD and their physicians. Meanwhile, this study provides useful information on the types of non-Hodgkin lymphomas that are increased from IBD treatment, namely the dreaded hepatosplenic T-cell lymphoma and cutaneous lymphomas.

— Douglas K. Rex, MD

Published in Journal Watch Gastroenterology February 8, 2013