Study finds no link between TNF-alpha blockers, cancer in inflammatory bowel disease

A large registry-based study has found no increased risk of cancer in inflammatory bowel disease patients treated with tumor necrosis factor alpha (TNF-alpha) antagonists. The findings, from the Danish National Patient Registry, are based on 56,146 inflammatory bowel disease (IBD) patients. "Given the upper limit of the conference intervals, this study could rule out a more than 36% relative increase in the risk of overall cancer over a median follow-up of 3.7 years among TNF-alpha antagonist-exposed patients, with 25% of these followed for 6 years or longer," Dr. Nynne Nyboe Andersen of Herlev University Hospital in Copenhagen told Reuters Health in an email. The findings are published in the June 18 issue of JAMA. Concerns had been raised that TNF-alpha antagonists might increase cancer risk through their immunosuppressive effects, Dr. Andersen and colleagues note in their report. Three studies of the issue have been done in IBD patients, with negative findings, but very short follow-up periods. In the current study, the researchers looked at IBD patients ages 15 years and older, including 4553 (8.1%) who had been treated with TNF-alpha antagonists. Their analysis included 489,433 person-years of follow-up, during which time 81 patients (1.8%) exposed to TNF-alpha antagonists developed cancer, and 3465 patients (6.7%) not exposed to the drugs were diagnosed with cancer. After Poisson regression analysis adjusting for age, calendar year, disease duration, propensity scores, and other IBD medication use, the relative risk associated with TNF-alpha antagonist use was 1.07, and not significant. The researchers also performed stratified analyses based on cumulative TNF-alpha antagonist dose and time since first TNF-alpha antagonist dose, but found no association with cancer risk. Their analysis also did not find an increased risk by cancer type. "Keeping in mind the often protracted progression of cancer, there is a need for future studies with an even longer follow-up time to evaluate the risk of cancer in patients exposed to TNF-alpha antagonists," Dr. Andersen said. "Further, it should be noted that due to the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancer and there is a need for larger future studies to assess the risk in different types of cancer." Dr. William Sandborn, director of the IBD Center at the University of California, San Diego, reviewed the study for Reuters Health. He noted that the issue of TNF-alpha and cancer risk in IBD has not been a major concern. However, he added, the IBD drugs azathioprine and 6-mercaptopurine have clearly been linked to cancer. "They are unequivocally linked with a higher risk of non-melanoma skin cancer and a higher risk of non-Hodgkin lymphoma," Dr. Sandborn said. Studies have shown that combination therapy with azathioprine and TNF-alpha antagonists is more effective than either drug given as monotherapy, he added. The question that needs to be answered, he said, is how the benefit of combination therapy compares to the increased cancer risk seen with azathioprine. "I hope the authors will continue to mine their data to further explore the relationship of the whole range of drugs we use in IBD and cancer," he said.