Introduction:
The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients.
Methods:
This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis.
Results:
93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none,
P
=0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%,
P
=0.04), PCI (0 vs. 0.5%,
P
=1), CABG (0. vs. 0.5%,
P
=1), stroke (0 vs. 0%), TIA (0 vs. 0.5%,
P
=1), DVT (5.4 vs. 2.2%,
P
=0.17), PE (1.1 vs. 4.8%,
P
=0.17), and myocarditis (2.2 vs. 1.1%,
P
=0.60). There was an increased rate of pneumonitis (14 vs. 4%,
P
<0.001) and skin toxicity (16 vs. 0%,
P
<0.001).
Conclusions:
Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.
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