Pre-existing autoimmune disease and the risk of immune-related adverse events among patients receiving checkpoint inhibitors for cancer
Patients with pre-existing autoimmune diseases have been excluded from clinical trials of immune checkpoint inhibitors (ICIs) for cancer. Real-world evidence is necessary to understand ICI safety in this population.
Patients treated with ICIs from 2011 to 2017 were identified using data from a large health insurer. Outcomes included time to (1) any hospitalization; (2) any hospitalization with an irAE diagnosis; and (3) outpatient corticosteroid treatment. The key exposure was pre-existing autoimmune disease, ascertained within 12 months before starting ICI treatment, and defined either by strict criteria (one inpatient or two outpatient claims at least 30 days apart) or relaxed criteria only (any claim, without meeting strict criteria).
Of 4438 ICI-treated patients, pre-existing autoimmune disease was present among 179 (4%) by strict criteria, and another 283 (6%) by relaxed criteria only. In multivariable models, pre-existing autoimmune disease by strict criteria was not associated with all-cause hospitalization (HR 1.27, 95% CI 0.998–1.62), but it was associated with hospitalization with an irAE diagnosis (HR 1.81, 95% CI 1.21–2.71) and with corticosteroid treatment (HR 1.93, 95% CI 1.35–2.76). Similarly, pre-existing autoimmune disease by relaxed criteria only was not associated with all-cause hospitalization (HR 1.11, 95% CI 0.91–1.34), but was associated with hospitalization with an irAE diagnosis (HR 1.46, 95% CI 1.06–2.01) and corticosteroid treatment (HR 1.46, 95% CI 1.13–1.88).
Pre-existing autoimmune disease was not associated with time to any hospitalization after initiating ICI therapy, but it was associated with a modest increase in hospitalizations with irAE diagnoses and with corticosteroid treatment.
KeywordsImmunotherapy Immune-related adverse event Checkpoint inhibitor Real-world evidence
Current procedural terminology
Healthcare common procedural coding system
Immune checkpoint inhibitor
Immune-related adverse event
Conceptualization: KLK. Data curation: KLK, SY, NP, and ISK. Formal analysis: KLK. Writing/original draft: KLK. Review and editing: all authors.
Supported by the National Cancer Institute (K05CA169384; Deborah Schrag).
Compliance with ethical standards
Conflict of interest
Dr. Awad reports serving in a consulting or advisory role to Abbvie; ARIAD Pharmaceuticals; AstraZeneca/MedImmune; Boehringer Ingelheim; Bristol-Myers Squibb; Clovis Oncology; Foundation Medicine; Genentech; Merck; Nektar; Novartis; Pfizer; and Syndax. He reports holding research funding from Bristol-Myers Squibb. A portion of Dr. Palmer’s salary is supported by Aetna to provide technical support in facilitating access to data used in this analysis; Dr. Palmer also holds research funding from Union Chimique Belge (UCB). Dr. Schrag reports serving as a consultant to Pfizer and Proteus. The other authors report no conflicts of interest.
Ethical approval and ethical standards
The Harvard Medical School Institutional Review Board waived the requirement for approval, deeming analysis of the database not to be human subjects’ research. The analysis and publication of the results were approved by Aetna, which provided the data.
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