Long-term use of thiopurines bears further study, researchers say
The use of thiopurine drugs to treat inflammatory bowel disease (IBD) increases the risk of cancers related to viral infection, according to a new study.
IBD includes Crohn's disease and ulcerative colitis. Thiopurine drugs are used to suppress the immune system in order to maintain remission in IBD patients.
For this study, French researchers analyzed data on 19,486 IBD patients (60 percent with Crohn's and 40 percent with ulcerative colitis or unclassified IBD) who were followed for a median of 35 months.
At the start of the study, 30 percent of patients were taking thiopurines, 14 percent had discontinued them, and 56 percent had never received thiopurines. During the study, 23 patients developed malignant lymphoproliferative disorders (LD) -- cancers that are associated with viral infection, particularly those linked to Epstein Barr virus (EBV) infection.
Of the 23 patients with LD, 22 had non-Hodgkin's lymphoma and one had Hodgkin's lymphoma. Incidence rates of LD were 0.90 per 1,000 patient-years in those receiving thiopurines, 0.20 per 1,000 patient-years in those who'd discontinued the drugs, and 0.26 per 1,000 patient-years in those who'd never taken thiopurines.
The researchers calculated that IBD patients taking thiopurines had a more-than-five-fold increased risk compared to those who'd never received the drugs. Older patients, men, and those who'd had IBD for longer were also at increased risk of LD.
"Extrapolating our results, the absolute cumulative risk of (LD) in young patients receiving a 10-year course of thiopurines remains low (less than 1 percent) 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," wrote Laurent Beaugerie, a professor at Hospital Saint-Antoine, Paris, and colleagues.
The study appeared online Monday and in an upcoming print issue of The Lancet.
"Although we recognize 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," Dr. Geert D'Haens, of the Imelda GI Clinical Research Centre and University Hospital Gasthuisberg in Belgium, and Dr. Paul Rutgeerts, University Hospital Gasthuisberg, wrote in an accompanying editorial.
SOURCE: The Lancet, news release, Oct. 18, 2009