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.

How many Italian cancer patients are eligible for, and may respond to, Italian Medicines Agency-approved immune checkpoint inhibitors?

“…The results of the present study may be useful for oncologists, policy makers, and any other stakeholder, in the debate about ICI, that includes the enthusiasms for the expected results but also doubts about their toxicity, 2,49 their effective real-world benefit 12 and the sustainability of their costs. 50…”

Association Between Oncology Clinical Pathway Utilization and Toxicity and Cost Outcomes in Patients With Metastatic Solid Tumors

“…12 Immune-related adverse events (IRAEs) included claims with diagnoses for complications such as endocrinopathies, hepatitis, and myocarditis, owing to immune checkpoint inhibitors. 13 The use of granulocyte colony-stimulating factor (G-CSF), erythropoietin-stimulating agent (ESA), antiemetics, and antidiarrheals was defined as having at least one claim with a Healthcare Common Procedure Coding System (HCPCS) or General Product Identifier (GPI) code for the respective drug. Cost variables were calculated using the allowed amount, which is a contractual amount between payer and provider and captures both plan-paid and out-of-pocket amounts (sum of all copayments, coinsurance, and deductibles), adjusted for inflation to 2021 dollars.…”

Management von Nebenwirkungen unter Immuncheckpointinhibition

“…In Kombination mit CTLA-4-Inhibitoren, wie in der Gynäkologie z. B. die Kombination aus Ipilimumab/Nivolumab im Off-Label Use bei fortgeschrittenem Zervixkarzinom, stieg der Anteil an immunvermittelten Nebenwirkungen signifikant an, insbesondere in Hinblick auf Pneumonitis, Endokrinopathien, Myokarditis, Hepatitis, Kolitis, Nephritis, Dermatitis und Enzephalitis [23].…”