Anti-TNF agents and thiopurines are associated with a slight increase in lymphoma in IBD patients

1. In this retrospective cohort study, inflammatory bowel disease (IBD) patients on anti-tumor necrosis factor (TNF) agents or thiopurines had a higher rate of developing lymphoma compared to non-exposed IBD patients.

2. The combination of both anti-TNF agents and thiopurines resulted in a higher risk or lymphoma than either alone.

Evidence Rating Level: 2 (Good)

Study Rundown: IBD treatment often requires anti-inflammatory agents to adequately control symptoms, and studies have suggested that the combination of thiopurines and anti-TNF agents may be more efficacious than either in isolation for severe cases. However, both of these agents have been associated with an increased risk of developing lymphoma, though the data for anti-TNF agents have been less consistent. In this French retrospective study of a health database covering 88% of the population, use of a thiopurine or an anti-TNF agent for IBD treatment resulted in a significantly increased risk of lymphoma, though the absolute increase in risk was slight. In addition, combination of both agents resulted in an even higher risk compared to either agent alone.

The completeness of French population covered by this study is a major strength, and the risks associated with these treatments in IBD patients is very likely to be real. However, in agreement with the study’s authors, it is likely that the slight increase in absolute risk will not preclude use of these agents for IBD treatment but will be of great importance when educating patients about the complications of this treatment.

Click to read the study in JAMA

Relevant Reading: Cancers Complicating Inflammatory Bowel Disease

In-Depth [retrospective cohort]: Using data from the French National Health Insurance Claim database (SNIIRAM), which contains data on 88% of the French population, prevalent and incident IBD cases were identified from 2009 to 2013 along with exposure to thiopurine, anti-TNF agents, or both in patients older than 18 years old. To exclude confounding variables associated with increased lymphoma risk, patients with HIV, organ transplants, or history of cancer were excluded. 189,289 IBD cases were identified that met inclusion/exclusion criteria with a median of 6.7 years of follow-up. When compared to non-exposed patients, those exposed to thiopurines (adjusted Hazard Ratio, aHR = 2.60; CI₉₅ 1.96-3.44) or anti-TNF agents (aHR = 2.41; CI₉₅ 1.60-3.64) had a higher risk of developing lymphoma, though the absolute risk increase was 0.28 and 0.15 per 1000 person years, respectively. In addition, there was an increased risk for a combination of both agents over either thiopurines (aHR = 2.35; CI₉₅ = 1.31-4.22) or anti-TNF agents (aHR = 2.53; CI₉₅ 1.35-4.77). There were no significant differences in risk between thiopurines or anti-TNF agents or between adalimumab or infliximab (p > 0.05), and several sensitivity analyses did not change these results.

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