Is There a Risk of Lymphoma Associated With Anti-tumor Necrosis Factor Drugs in Patients With Inflammatory Bowel Disease? A Systematic Review of Observational Studies

Background: Inflammatory bowel diseases (IBDs) are generally not considered a risk factor for the development of lymphoma. When considering IBD treatments, there is good evidence supporting thiopurines (azathioprine, 6-mercaptopurine) as a risk factor for lymphoma. Conversely, the association between the use of anti-TNF agents and the development of lymphoma remains undetermined. In this systematic review, we analyzed the evidence coming from observational studies supporting an association between the use of anti-TNF drugs and lymphoma in patients with IBDs. Methods: This systematic review was performed according with MOOSE and PRISMA statements. We searched observational studies conducted on IBD patients, using MEDLINE, EMBASE, and Google Scholar, published in English language, within the period ranging from January 1st, 1999 to June 30th, 2018. An assessment of the methodologic shortcomings of selected studies was performed as well. Results: Fourteen studies met the eligibility criteria and were included in the review. Only four studies found a significant association of anti-TNF drug with lymphoma or groups of cancers including lymphoma. However, the methodologic shortcomings of all the included studies made their results unreliable, irrespectively of whether their findings supported an association or not. Conclusions: Current evidence from observational studies does not allow excluding or confirming an association of the exposure to anti-TNF treatments with lymphoma in IBD patients.