According to the results of a cohort study, use of thiopurines and anti-TNF medications for the treatment of inflammatory bowel disease (IBD) may increase the risk of lymphoma.

The authors note that the US FDA has previously expressed concern that medications used to treat IBD may increase the risk of lymphoma; most attention has been focused on thiopurines (azathioprine and 6-mercaptopurine) and the anti-TNF agents.  In this study, they sought to evaluate the relationship between IBD, immonomodulating therapy and lymphoma in a cohort of patients registered in the Kaiser Permanente (US).

The study included patients without HIV who had at least one year of enrolment and at least two inpatient or outpatient diagnosis codes for IBD.  Data on medications dispensed were identified from pharmacy data and incident cases of lymphoma reported after IBD diagnosis were obtained from the Kaiser Permanente Cancer Registry.  Four medication exposure groups were considered: 1) thiopurine only; 2) anti-TNF only; 3) both thiopurine and anti-TNF; 4) neither drug class (those using the two drug classes sequentially were considered exposed to two monotherapies). 

The incidence rate of lymphoma in relation of thiopurine and anti-TNF use for patients with IBD was calculated, and lymphoma incidence was compared between the IBD cohort and the general Kaiser Permanente population.  Standardised incidence rate ratios (SIRRs) were estimated by comparing the observed number of incident lymphoma cases in the IBD cohort to the expected number in the general Kaiser Permanente population without IBD.

The main results reported are as follows:

• A total of 16,023 patients with IBD were followed for an average 5.8 years, 43 of whom developed lymphoma (most commonly diffuse large B-cell lymphoma [44%], follicular lymphoma [14%], and Hodgkin's disease [12%]).

• Of the 21,282 person-years involving exposure to thiopurine or anti-TNF, 81% involved thiopurine alone; 3%, anti-TNF alone; and 16% involved combination therapy.

• Patients with IBD who had no record of a dispensing of a thiopurine or anti-TNF were not found to be at an increased risk of lymphoma relative to the general population (SIRR of 1.0; 95% CI 0.96–1.1).

• The risk of lymphoma was found to be increased among current users of thiopurines [but not anti-TNFs] (SIRR 1.4; 95% CI 1.2–2.7) but not in past users (SIRR 0.3; 95% CI 0.2–0.4)

• Exposure to therapy including anti-TNFs (with or without thiopurines) was associated with an increased risk of lymphoma (SIRR of 5.5 [95% CI 4.5–6.6] for past use and 4.4 [95% CI 3.4–5.4] for current use. [There was insufficient data available to allow determination of the risk associated with anti-TNF therapy alone]

The authors comment that the results of this observational study should be interpreted with caution due to lack of control over unmeasured confounders that may have influenced both medication use and risk of lymphoma.  They also note that the medication history may have been incomplete. 

They summarise that they found no increased risk of lymphoma among IBD patients without a recorded dispensing of a thiopurine or anti-TNF agent (indicating mild IBD); even with combined therapy the age-standardised incidence rate was 113.8 per 100,000 person-years.  They comment that this absolute incidence rate is important when putting potential benefits and risks of treatment into perspective.