Immune checkpoint inhibitors: immune-related adverse events, healthcare utilization, and costs among commercial and Medicare Advantage patients

Abstract

Background: Immune checkpoint inhibitors (ICI) are increasingly used across multiple cancer types and stages and little is known about real-world outcomes. This study sought to determine healthcare utilization, costs, immune-related adverse events (irAEs), and all-cause mortality of single-agent versus combination ICI in the USA. Materials and methods: This is a retrospective study conducted with 2016–2018 data from the HealthCore Integrated Research Database, consisting of commercial and Medicare-insured adult patients with a cancer diagnosis using ICI in the USA. Outcomes were healthcare utilization, costs, and irAEs (FDA-recognized and others) up to 1-year post-index between patients using ICI monotherapy (mono, PD-1/PD-L1 inhibitor) and combination therapy (combo, PD-1/PD-L1 with CTLA-4 inhibitors). Results: In total, 9084 patients received monotherapy and 904 patients received combo therapy. Mean age 65 years for mono and 58 years for combo. Overall, the combo arm had higher rates of FDA-recognized irAEs (67.4% vs. 45.9%), especially endocrinopathies (27.7% vs 14.7%) and dermatitis (25.9% vs. 12.4%). All-cause mortality over 1-year follow-up was similar, 30.7% in mono vs 30.8% in combo arms. The combo group had higher rates of all-cause inpatient hospitalizations (55.4% mono vs 65.6% combo) and emergency department (ED) visits (33.7% mono vs 41.4% combo). IrAE-related hospitalizations were higher in combo (55.2% vs 42.1%). IrAE-related ED visits were 15.7% mono vs 22.7% combo. This increased toxicity and health care utilization was reflected in significant differences in healthcare costs. Stark differences were seen in all-cause medical costs as well as costs related to inpatient and ED utilization and costs attributed to irAEs. Conclusions: Higher rates of irAEs, healthcare utilization, and costs occur with combination immunotherapy. As further indications are approved for combination ICI, our study highlights the real-world tradeoffs involved with combination therapy regarding burdens of toxicity and increased healthcare utilization.