Autoimmune side-effect of immunotherapy in lung cancer treatment revealed from large-scale cohort

Although immune checkpoint inhibitors have illustrated strong benefits in patient survival and have been widely acknowledged in treating lung cancer, they may be subject to increased risk of immune-related adverse effects (irAEs). Although existing literature have studied the mechanisms of irAEs of immunotherapy, it is difficult to quantify such effect, especially at a large-scale real-world population level. In this paper, the autoimmune-related risk of multiple immune checkpoint inhibitors is compared with that of chemotherapy based on Medicaid and CHIP TAF (T-MSIS Analytic File) data of over 100,000 patient samples from 2012 to 2018. Results show that the irAEs of immunotherapy is significantly higher than chemotherapy in both unadjusted and adjusted samples from the dataset. Analysis on subpopulation and specific disease types further shows that certain immunotherapy treatments are associated with higher risk of irAEs, and the risk of certain autoimmune diseases may vary. We also illustrate the robustness of our conclusion through additional sensitivity analysis, confirming the necessity of keeping track of autoimmune side effects of immune checkpoint inhibitors for medicine researchers. Our methods are also available to evaluate effectiveness and side effects of novel therapies at a large-scale population level.