Tumor necrosis factor (TNF) inhibitors, which are used to reduce inflammation in diseases like rheumatoid arthritis and Crohn’s, have been suspected to increase the risk of cancer. But a new study shows that these medications do not increase the risk of cancer, at least in the short-term.
The study, published in the Journal of the American Medical Association (JAMA), included more than 56,000 patients with inflammatory bowel diseases (IBDs). The researchers studied cancer rates in IBD patients taking TNF-alpha antagonists, compared with IBD patients who were not exposed to these medications.
TNF-α antagonists have been shown to be beneficial in reducing inflammation in inflammatory diseases like rheumatoid arthritis and ulcerative colitis.
The researchers found that tumor necrosis factor alpha antagonists did not increase the risk of cancer over a median follow-up of about 4 years, although an increased risk of cancer in the long-term, or with an increasing number of doses, cannot be excluded, according to the study’s authors.
TNF-alpha antagonists were given to 4,553 patients, or 8.1 percent of patients in the study. In total, 3,465 patients with IBD unexposed to TNF-α antagonists and 81 exposed to the drugs developed cancer.
The results indicated that exposure to TNF-α antagonists is not associated with an increased overall cancer risk or a rise in the risk of site-specific cancers.
Speaking to Healthline, lead study author, Dr. Nynne Nyboe Andersen of the department of epidemiology research at Statens Serum Institut in Copenhagen, Denmark said, “The TNF-alpha inhibitors were introduced in the late 1990s, and the use of these drugs is increasing worldwide for treatment of different chronic inflammatory conditions, such as rheumatoid arthritis and IBD. TNF-alpha is a cytokine involved in systemic inflammation; but the cytokine is also involved in the regulation of tumor growth; therefore, an initial concern was raised about a potential increased risk of malignancy related to these drugs.”
Dr. Randall F. Holcombe, a professor of medicine in the division of hematology and medical oncology, and director of Clinical Cancer Affairs for the Icahn School of Medicine at Mount Sinai in New York, told Healthline, “There has been a concern that the use of the anti-tumor necrosis factor agents might lead to an increased incidence of colon cancer, specifically, and possibly other cancers in patients with IBD. They are very useful agents for the treatment of IBD, so they are being used more and more. They definitely suppress the immune system. The concern is they may also be suppressing anti-cancer immune surveillance mechanisms, which would then allow the development of cancer. We know that patients with IBD are more at risk for the development of intestinal cancers, anyway, because of the underlying condition…That hasn’t limited their use, but it’s been a concern in the medical community.”
Previous studies of the risk of cancer associated with these medications were based on data from randomized clinical trials with a short follow-up time, which is not suitable for studying a potential cancer risk, Andersen said.
Andersen added that the current study can rule out a more than 36 percent relative increase in the overall risk of cancer over a median follow-up of 3.7 years among TNF-α antagonist-exposed patients, 25 percent of whom were followed for six years or longer. “We also did stratified analyses according to a cumulative number of TNF-α inhibitor doses, and time since first TNF-α inhibitor dose, but these results did not reveal any significantly increased risk of cancer, nor did the analyses on subgroups of cancer,” she said.
Pointing out that the study provides doctors with an updated safety profile regarding the risks of TNF-α antagonists in Danish IBD patients, Andersen said she is hopeful that “these results can most likely be extended to other Western countries.”
Andersen cautioned that continuous follow-up of exposed patients is needed, since the study did not have a sufficient number of patients to make a clear evaluation about the risk of site-specific cancers. Also, an increased risk of cancer in the long-term, or with an increasing number of cumulative doses of TNF-α antagonists, cannot be ruled out.
Holcombe added, “This study is an observational study of a large number of patients, though it is a relatively small number of patients in the group that actually got treated with the TNF-alpha antagonists. But they did not see any increase in cancer in the patients who were receiving this medication. I think that is reassuring, because it suggests there isn’t a dramatic increase that would necessitate changing treatment modalities for patients with IBD. It’s not definitive that these agents don’t lead to an increase in cancer, but it certainly is suggested that the concerns are not as serious as we may have thought.”
Noting that colon cancer develops between five and ten years after a cell becomes abnormal, or after a genetic mutation occurs that leads to the development of a cancerous cell, Holcombe said it may actually be five to ten years before cancer appears in IBD patients.
“That’s a long period of time, and the researchers only studied 3.7 years, which is a relatively short period of time,” Holcombe said. “In IBD the time is compressed somewhat, so we think patients who develop intestinal cancer with IBD develop cancer on a faster timeline than patients without IBD. There has to be continued follow-up of this patient group, so they are followed up five or even ten years, to really get a better assessment as to the rate of development of cancer in these patients that do and don’t get these TNF antagonists.”