Thiopurines and anti-TNF therapy appear to be associated with a small but significantly increased risk of lymphoma in patients with IBD.

A French study identified 336 lymphoma cases in more than 189,000 patients with IBD followed for a median of seven years.

Patients not exposed to either drug had an incidence rate of lymphoma of 0.26 per 1000 person-years compared to 0.54 with thiopurine monotherapy, 0.41 with anti-TNF monotherapy and 0.95 with combination therapy.

More than a third (35%) of patients on anti-TNF therapy had previously been exposed to thiopurines while only 6% of patients on thiopurines had previously used anti-TNFs.

Commenting on the study, Associate Professor Graham Radford-Smith, head of IBD and TPN services at the Royal Brisbane and Women’s Hospital, said the findings were largely consistent with other studies.

“A meta-analysis has also been done demonstrating a standardized incidence rate of lymphoma with respect to thiopurines of around 2.8 which is very similar to the hazard ratio generated with respect to thiopurines in the French study.”

He told the limbic that while the risk of lymphoma increased with therapy in relative terms, the study found the absolute risk was less than 1 case per 1000 person-years.

“The treating gastroenterologist or IBD specialist should be discussing the benefits and risks of taking any medications and especially with a young population with IBD.”

He said the best way to educate patients about their level of risk was to use diagrammatic representations rather than giving statistical information.

“These drugs do remain very safe when you look at absolute risk as compared to relative risk.”

The study also found increasing age, male gender, a diagnosis of Crohn’s disease, and smoking related conditions were associated with an increased risk of lymphoma.

Associate Professor Radford-Smith said therapeutic drug monitoring could be useful in determining response to treatment but also potential opportunities to downscale or withdraw therapy.

“There is plenty of data that demonstrates combination therapy work best and reduces the side effect profile with infliximab but not adalimumab. However there is still some work to do to determine how long to continue thiopurines when you have a chimeric anti-TNF like infliximab.”

“Ideally we would like to see scaling back thiopurines, if one can, while continuing anti-TNF monotherapy.”

There was also the potential to reduce exposure to anti-TNFs for patients in deep remission for a period of time.