Health care use and costs associated with clinically impactful immune-related adverse events during immune checkpoint inhibitor therapy for non-small cell lung cancer.

backgroundImmune checkpoint inhibitors (ICIs) are widely used in advanced non-small cell lung cancer (NSCLC) but can lead to immune-related adverse events (irAEs) that may disrupt care. Although irAEs are well described clinically, there is limited evidence quantifying their downstream health care use and costs in Medicare beneficiaries with advanced NSCLC.

objectiveTo evaluate health care use and costs associated with clinically impactful irAEs among older adults receiving ICI therapy.

methodsUsing Surveillance, Epidemiology, and End Results-Medicare data, we identified patients (fee-for-service beneficiaries) aged 66 to 85 years with advanced NSCLC and who initiated nivolumab, pembrolizumab, or atezolizumab, alone or in combination with each other or chemotherapy, between 2015 and 2017 (patient identification window), with follow-up through 2019. These agents represent ICIs approved for advanced NSCLC during the identification period. Clinically impactful irAEs were defined using irAE diagnosis codes accompanied by evidence of systemic immunosuppressant use and treatment interruption and were modeled as a time-varying exposure. Health care use and costs were assessed using weighted longitudinal models accounting for time-varying confounding (marginal structural models with stabilized inverse probability weights). Two-part generalized estimating equations estimated per-patient-per-month (PPPM) and cumulative outcomes over 6, 12, and 24 months, with sensitivity analyses including models incorporating ICI drug costs and alternative approaches to account for censoring.

resultsAmong 4,867 patients, 1,667 (34.3%) experienced a clinically impactful irAE. Adjusted all-cause health care use was higher among patients with irAEs (mean 15.8 [SE = 0.12] vs 12.0 [SE = 0.12] visits PPPM; difference, 3.9; 95% CI = 2.9-4.8), with more than double the odds of inpatient hospitalization (odds ratio, 2.21; 95% CI = 2.15-2.29). Adjusted all-cause medical costs averaged $16,042 (SE = 14.7) vs $12,721 (SE = 13.1) PPPM (difference, $3,322; 95% CI = $3,283-$3,361), driven primarily by inpatient care ($2,922; 95% CI = $2,903-$2,941). At 24 months, cumulative costs per patients were $846,013 (SE = 12,786) for patients with irAEs compared with $751,606 (SE = 11,358) for those without (difference, $94,407; 95% CI = $91,606-$97,207). Findings were consistent in sensitivity analyses.

conclusionsClinically impactful irAEs were associated with substantially higher health care use and costs among older adults with advanced NSCLC receiving ICIs, with inpatient care accounting for most excess costs. These findings have implications for managed care strategies focused on toxicity monitoring, hospitalization prevention, and value-based ICI management.