The tumor necrosis factor–alpha antagonists infliximab, adalimumab, and certolizumab did not raise the risk of cancer in a nationwide Danish cohort study of patients with inflammatory bowel disease who were followed for approximately 10 years, according to a report published online June 17 in JAMA.
At present, the effectiveness of these agents in inflammatory bowel disease (IBD) must be weighed against their potential adverse effects, which include immunosuppression that is suspected to increase the risk of cancer. But few studies have examined this risk, and those that have done so have had short (less than 1 year) exposure and follow-up times, said Dr. Nynne Nyboe Andersen of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.
Dr. Nynne Nyboe Andersen
They assessed the risks of any cancer and of 11 individual cancers in 56,146 IBD patients aged 15 and older living in Denmark in 1999-2012, of whom 4,553 took TNF-alpha antagonists. Median follow-up was 9.3 years, and median duration of therapy with TNF-alpha antagonists was 3.7 years. The two study groups were propensity matched for year of birth, sex, socioeconomic status, comorbidities, use of other medications, subtype of IBD, and history of gastrointestinal or anal fistula, abscess, fissure, or surgery.
A total of 6.7% of the patients who never took TNF-alpha antagonists developed cancer during follow-up, compared with 1.8% of patients who took the drugs, indicating no increase in cancer risk associated with TNF-alpha antagonists. Further analyses of the data found no association between use of these agents and the risk of overall cancer, regardless of the patient’s sex, age, the duration of therapy, or the cumulative dose, and sensitivity analyses confirmed these results, the investigators said (JAMA 2014 June 17 [doi:10.1001/jama.2014.5613]).
There also was no association between use of TNF-alpha antagonists and any individual cancer. "However, it should be noted that because of 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 cancers," Dr. Andersen and her associates said.
"Stratifying for cancer risk according to years since first exposure, no specific time-dependent pattern was observed in our study. However, considering the often protracted progression of cancer, an increased risk in the long term cannot be excluded, and future studies with longer follow-up are needed," they added.
The Lundbeck Foundation, Danish Cancer Society, Crohn’s and Colitis Association of Denmark, and Danish Council of Independent Research supported the study. Dr. Andersen reported receiving funding from Merck Sharp & Dohme; her associates reported ties to Merck Sharp & Dohme, Tillotts, Calpro, Ferring, and AbbVie.