Patients who receive thiopurines for inflammatory bowel disease are at increased risk for lymphoproliferative disorders, but the overall incidence is low and the benefits of treatment for IBD still outweigh the risks, according to data from more than 19,000 adults.
“We have shown that risk of lymphoproliferative disorders was five times higher in patients exposed to thio-purines than in those never exposed to the drugs,” wrote Dr. Laurent Beaugerie of Saint Antoine Hospital, Paris, and colleagues in their report of the prospective, observational cohort study.
But the results also indicate absolute cumulative risks of lymphoproliferative disorders among patients who continue to take thiopurines at less than 1% in patients younger than 50 years, less than 3% in patients aged 50-65 years, and less than 6% in patients older than 65, the researchers said.
The team reviewed data from the CESAME (Cancers et Surrisque Associe aux Maladies Inflammatories Intestinales en France) study, which was designed to assess various risks of taking thiopurines for IBD. The study included 11,759 adults with Crohn's disease and 7,727 adults with ulcerative colitis or unclassified IBD (Lancet 2009 Oct. 18 [Epub doi:10.1016/S0140-6736(09)61302-7]).
At baseline, 5,867 patients were receiving thiopurines, 2,809 patients had discontinued thiopurines, and 10,810 patients had never received thiopurines. Patients were recruited into the study between May 2004 and June 2005, and the researchers followed them until Dec. 31, 2007, an average of 35 months.
During the study period, 114 (2%) of patients who were receiving thio-purines at baseline developed cancer, compared with 41 (1%) of patients who had discontinued the drugs and 134 (1%) of patients who had never taken them. A total of 22 patients were diagnosed with non-Hodgkin's lymphoma, and 1 patient was diagnosed with Hodgkin's lymphoma during 49,713 patient-years of follow-up.
Old age, being male, and longer disease duration were associated with an increased risk of lymphoproliferative disorders.
“Our hypothesis of a constant risk of lymphoproliferative disorder during thiopurine therapy is supported by three considerations,” they said. First, the consistent dose of immunosuppressants in a post-transplant setting keeps the risk for lymphoma constant. Second, the same number of lymphomas was seen during the first and third years of the study. Finally, “the duration of previous thiopurine exposure was evenly distributed among the 23 patients who developed lymphoma.”
Patients who discontinued therapy had more clinically active IBD but a lower risk of lymphoproliferative disorders compared with those receiving thio-purines. Dr. Beaugerie has received funding from UCB Pharma, Sanofi-Aventis, Abbott, and Ferring Pharmaceuticals.