No Increased Risk for Cancer in Patients Receiving Tumor Necrosis Factor–Alpha Antagonists for Inflammatory Bowel Disease
Some data indicate an increased risk for cancer in patients receiving tumor necrosis factor (TNF)-alpha antagonists (eg, infliximab [Remicade], adalimumab [Humira], certolizumab pegol [Cimzia]) for rheumatoid arthritis. Studies with follow-up of ≤ 1 year have not found increased risk in patients receiving these agents for inflammatory bowel disease (IBD). In a Danish study reported in JAMA, Andersen et al found no increased risk of cancer in patients receiving TNF-alpha antagonists for IBD over a median follow-up of 3.7 years. However, a nonsignificantly increased risk was associated with receipt of a greater number of doses and longer time from first dose.
The study involved 56,146 patients aged ≥ 15 years with IBD diagnosed between 1999 and 2012 from the Danish National Patient Registry, including 4,553 (8%) with exposure to TNF-alpha antagonists. Cancer cases were identified from the Danish Cancer Registry.
No Increased Risk
During 489,433 person-years of follow-up, representing a median of 9.3 years among all IBD patients, cancer developed in 81 patients exposed to TNF-alpha antagonists (1.8%, median follow-up of 3.7 years) and 3,465 of 51,593 of unexposed patients (6.7%). Exposure to TNF-alpha antagonists was not associated with increased overall cancer risk in crude analysis (rate ratio [RR] = 1.07, 95% confidence interval [CI] = 0.86–1.33); risk was significantly increased in analysis adjusting for age, calendar year, disease duration, propensity scores, and use of IBD medications except azathioprine (RR = 1.25, 95% CI = 1.00–1.58), but not in analysis that also adjusted for azathioprine use (RR = 1.07, 95% CI = 0.85–1.36).
Effect of Greater Dose, Time Since Start?
There was no significantly increased risk associated with TNF-alpha exposure in analyses stratified by age group, cumulative number of TNF-alpha antagonist doses, and time since first dose. However, adjusted rate ratios were nonsignificantly increased in patients with the highest number of accumulated doses (≥ 8; 1.29, 95% CI = 0.90–1.85) and in those with ≥ 5 years since initial exposure (1.33, 95% CI = 0.88–2.03).
On fully adjusted analysis, TNF-alpha antagonist exposure was not associated with increased or decreased risk of any site-specific cancer.
The investigators concluded, “In this Danish nationwide study, exposure to [TNF-alpha] antagonists among patients with IBD was not associated with an increased risk of cancer over a median follow-up of 3.7 years among those exposed. An increased risk associated with longer-term accumulated doses and follow-up cannot be excluded.”
Nynne Nyboe Andersen, MD, of the Statens Serum Institut, Copenhagen, is the corresponding author for the JAMA article.
The study was supported by grants from the Lundbeck Foundation, Danish Cancer Society, and Crohn’s & Colitis Association of Denmark. For full disclosures of the study authors, visit jama.jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
