The evidence is conflicting as to whether long-term thiopurine therapy to suppress the immune system increases the risk of developing lymphomas in patients with IBD. Laurent Beaugerie and co-workers now present evidence from the large, prospective, observational CESAME study that patients with IBD receiving thiopurines have an increased risk of developing lymphoproliferative disorders. “A prospective trial from GETAID had demonstrated that azathioprine withdrawal after 4 years of efficacy resulted in a high rate of relapse in the next 2 years,” explains Beaugerie, so they questioned whether it is possible to “give thiopurines for very long periods without exposing patients to a high risk of cancers associated with thiopurine therapy.”

The researchers, from several French institutions, assessed the incidence of lymphoproliferative disorders in 19,486 individuals with IBD (almost two-thirds of whom had Crohn's disease) who were subdivided dependent on whether they were currently receiving (30.1%), had discontinued (14.4%) or had never received (55.5%) thiopurine therapy.

The investigators found that the incidence rate of lymphoproliferative disorders in patients on thiopurine therapy at ≥1 year of follow-up was 0.9 per 1,000 patient-years, while incidence rates of 0.2 and 0.26 per 1,000 patient years were recorded in patients who discontinued or never received thiopurine therapy, respectively. Following statistical analysis of the data, Beaugerie's team noted a fivefold increase in the risk of lymphoproliferative disorders for individuals on thiopurine therapy in comparison with those who had never received thiopurines.

The researchers also identified old age, male sex and longer duration of IBD (increasing with each additional year of disease) as risk factors for lymphoproliferative disorders, and so are hesitant to dismiss the use of long-term thiopurine therapy in certain settings. “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. For elderly patients and unlimited treatment periods, the question should be addressed in dedicated studies,” conclude the researchers.