Pre-existing autoimmune disease and the risk of immune-related adverse events among patients receiving checkpoint inhibitors for cancer

Cancer Immunol Immunother. 2019 Jun;68(6):917-926. doi: 10.1007/s00262-019-02321-z. Epub 2019 Mar 15.

Abstract

Introduction: 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.

Methods: 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).

Results: 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).

Conclusion: 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.

Keywords: Checkpoint inhibitor; Immune-related adverse event; Immunotherapy; Real-world evidence.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology*
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology*
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Insurance, Health / statistics & numerical data
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms / complications
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology*

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor