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Unresolved issue: should patients with RA and a history of malignancy receive anti-TNF therapy?

Nature Clinical Practice Rheumatology volume 3, pages 120–121 (2007)Cite this article

Anti-tumor necrosis factor (TNF) therapy is widely used for the treatment of patients with rheumatoid arthritis (RA) refractory to conventional therapy. But does anti-TNF therapy increase the risk of new or recurrent malignancy in patients with previous malignancy and, if so, should these individuals avoid the use of anti-TNF therapy? To date, no study has conclusively addressed this question. To help clinicians gauge the risks and benefits of initiating anti-TNF therapy in patients with RA and pre-existing malignancy, we evaluated the existing literature and searched the FDA website for post marketing data on anti-TNF therapy and malignancy risk.

Studies have shown that patients with RA have a higher risk of developing lymphoma (particularly non-Hodgkins lymphoma), and possibly a higher risk of developing lung cancer, than the general population.1,2,3,4 By contrast, patients with RA seem to have a reduced risk of developing colorectal cancer, a finding that might be attributable to the protective effect of NSAIDS.2,4 Several studies have implied that anti-TNF therapy is associated with an increased risk of developing lymphoma over and above that of RA itself. A large prospective study of 18,572 patients with RA in the US indicated that, compared with the general US population, the standard incidence ratio for lymphoma in patients treated with infliximab or etanercept was 2.9 (95% CI 1.7–4.9), in methotrexate-treated patients was 1.7 (95% CI 0.9–3.2), and in patients receiving none of these treatments was 1.0 (95% CI 0.4–2.5).5 It should be pointed out, however, that comparison of a population of patients with RA with the general US population is not appropriate because the general US population does not have the morbidity and mortality risks that are associated with RA. Moreover, although this study found an increased risk of lymphoma in patients treated with anti-TNF therapy, this finding might be the result of a 'channelling bias', whereby patients with RA who have the highest risk of developing lymphoma as a consequence of having severe disease are the ones who are most likely to receive anti-TNF therapy. In support of the above findings, a community-based Swedish study with a follow-up period of up to 5 years indicated a modest increase in the risk of developing lymphoma (but not solid tumors) in patients treated with anti-TNF therapy (226 patients treated with etanercept and 531 patients treated with infliximab), compared with a control group of 800 patients with conventionally treated RA. The relative risk of lymphomas was 4.9 (95% CI 0.9–26.2).6

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Authors and Affiliations

  1. A Brar is a Rheumatology Fellow and T Hiebert is an Internal Medicine Resident at the University of Manitoba, and H El-Gabalawy is Professor of Medicine and Immunology Director at the Arthritis Centre, University of Manitoba, Winnipeg, Canada.,

    Adarshdip Brar, Timothy Hiebert & Hani El-Gabalawy

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  1. Adarshdip Brar
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Correspondence to Hani El-Gabalawy.

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Brar, A., Hiebert, T. & El-Gabalawy, H. Unresolved issue: should patients with RA and a history of malignancy receive anti-TNF therapy?. Nat Rev Rheumatol 3, 120–121 (2007). https://doi.org/10.1038/ncprheum0434

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