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. 2022 Dec 20;4(5):660-669.
doi: 10.1016/j.jaccao.2022.11.008. eCollection 2022 Dec.

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

Charlotte Lee  1 , Zsofia D Drobni  2   3 , Amna Zafar  4 , Carlos A Gongora  2 , Daniel A Zlotoff  5 , Raza M Alvi  2 , Jana Taron  6 , Paula K Rambarat  7 , Sara Schoenfeld  8 , Ramya C Mosarla  9 , Vineet K Raghu  2 , Sarah E Hartmann  2 , Hannah K Gilman  2 , Sean P Murphy  5 , Ryan J Sullivan  10 , Alexander Faje  11 , Udo Hoffmann  2 , Lili Zhang  12 , Thomas Mayrhofer  2 , Kerry L Reynolds  10 , Tomas G Neilan  2   13
Affiliations

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

Charlotte Lee et al. JACC CardioOncol. .

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.

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Conflict of interest statement

Dr Neilan is supported by gifts from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award; and is supported by grants from the National Institute of Health/National Heart, Lung, and Blood Institute (R01HL30539, RO1HL137562, and K24HL150238). Dr Drobni was supported by the ÚNKP-22-4-II-SE New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development, and Innovation fund. Dr Neilan has been a consultant to and received fees from H3-Biomedicine, Abbvie, Roche, C-4 Therapeutics, Sanofi, CRO Oncology, Genentech, and Amgen, outside of the current work; has received consulting fees from Bristol Myers Squibb for advice focused on myocarditis related to ICIs; and has received grant funding from AstraZeneca and Bristol Myers Squibb. Dr Taron has received funding from Deutsche Forschungsgesellschaft (TA 1438/1-2.T); and is a member of the Speakers Bureaus of Siemens Healthineers and Bayer, unrelated to this work. Dr Hoffmann has received consulting fees from Abbott, Duke University (National Institutes of Health), and Recor Medical, outside the submitted work; and has received research grants from Medimmune, HeartFlow, AstraZeneca, and KOWA. Dr Sullivan has been a consultant to Asana, AstraZeneca, Bristol Myers Squibb, Eisai, Iovance, Merck, Novartis, Pfizer, OncoSec, and Replimune; and has received research funding from Amgen and Merck, all outside the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Kaplan-Meier Curves of Cardiovascular Events in Patients With and Without AD There was a significant difference (P = 0.02) in event-free survival between those with pre-existing autoimmune disease (AD) (n = 251) and those without pre-existing AD (n = 251). P value based on Cox model with shared frailty for composite event.
Central Illustration
Central Illustration
Baseline Autoimmune Disease Increases Risk for CV Events After Immunotherapy Patients with autoimmune disease (AD) have increased cardiovascular (CV) risk. Immune checkpoint inhibitor (ICI) therapy can also increase CV events. There was a close to 2-fold increase in CV events in patients with baseline AD who received ICI therapy, suggesting need for close surveillance. CABG = coronary artery bypass graft; DVT = deep venous thrombosis; FU = follow-up; MI = myocardial infarction; PCI = percutaneous coronary intervention; PE = pulmonary embolism; TIA = transient ischemic attack.
See this image and copyright information in PMC

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