MedicalResearch: What are the main findings of the study?
Dr. Andersen: Previous studies evaluating the risk of cancer associated with the use of TNF-α antagonists are mainly based on data from randomized clinical trials with a short follow up time. Consequently, we used the national Danish registries to conduct a nationwide population-based cohort study assessing the risk of cancer in patients with inflammatory bowel disease (IBD) exposed to these drugs from their introduction in 1999 until 2012. We included more than 56.000 patients with IBD and among those 4500 were exposed to TNF-α antagonists, contributing with almost 20.000 person-years of follow-up.
Our main results revealed that the risk of overall cancer was significantly increased in the analysis adjusted for propensity score and potential confounders except for azathioprine, however, when we additionally adjusted for azathioprine use the relative risk decreased markedly leaving no significant increased risk of cancer. Given the upper limit of the confidence 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-α antagonist-exposed patients with 25% of these followed for 6 years or longer. We also did some stratified analyses according to 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 site-specific cancers.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Andersen: The study confirms and expands on previous literature and provides reassuring results on the long-term safety of TNF-α antagonists. Although a small increase in the risk of overall cancer may be observed in patients exposed to TNF-α antagonists, this increase in risk might be attributable to concomitant use of azathioprine. Thus, our study provides the clinicians with an updated safety profile regarding malignancy risk associated with TNF-α antagonists based on the entire Danish IBD population and these results can most likely be extended to other Western countries. For the patients our study provides reassuring results and may therefore facilitate the decision between clinicians and patients whether or not to begin or continue treatment.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Andersen: Keeping in mind the often protracted progression of cancer there is a need of continuous population-based studies with even longer follow up time. Further, our study was not powered to rule out a more than 2-fold increased risk of different site-specific cancers including skin cancer, hematopoietic and lymphoid tissue cancer and there is a need of even larger scale population-based study to assess this. Further, there is a lack of data regarding the cancer risk of the different TNF-α antagonists separately.