Pre-Existing Autoimmune Disease Increases the Risk of Cardiovascular and Noncardiovascular Events After Immunotherapy

Abstract

Background: The use of immune checkpoint inhibitors (ICI) is associated with cardiovascular (CV) events, and patients with pre-existing autoimmune disease are at increased CV risk.

Objectives: The aim of this study was to characterize the risk for CV events in patients with pre-existing autoimmune disease post-ICI.

Methods: This was a retrospective study of 6,683 patients treated with ICIs within an academic network. Autoimmune disease prior to ICI was confirmed by chart review. Baseline characteristics and risk for CV and non-CV immune-related adverse events were compared with a matched control group (1:1 ratio) of ICI patients without autoimmune disease. Matching was based on age, sex, history of coronary artery disease, history of heart failure, and diabetes mellitus. CV events were a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or myocarditis. Univariable and multivariable Cox proportional hazards models were used to determine the association between autoimmune disease and CV events.

Results: Among 502 patients treated with ICIs, 251 patients with and 251 patients without autoimmune disease were studied. During a median follow-up period of 205 days, there were 45 CV events among patients with autoimmune disease and 22 CV events among control subjects (adjusted HR: 1.77; 95% CI: 1.04-3.03; P = 0.0364). Of the non-CV immune-related adverse events, there were increased rates of psoriasis (11.2% vs 0.4%; P < 0.001) and colitis (24.3% vs 16.7%; P = 0.045) in patients with autoimmune disease.

Conclusions: Patients with autoimmune disease have an increased risk for CV and non-CV events post-ICI.

Keywords: CABG, coronary artery bypass graft; CTLA-4, cytotoxic T lymphocyte–associated antigen-4; CV, cardiovascular; DVT, deep venous thrombosis; ICI, immune checkpoint inhibitor; MI, myocardial infarction; PCI, percutaneous coronary intervention; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; PE, pulmonary embolism; SMD, standardized mean difference; TIA, transient ischemic attack; coronary artery disease; immunotherapy; irAE, immune-related adverse event; myocarditis; thrombosis.