Patient-Reported Burden and Clinical Spectrum of Rheumatic Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy in Lung Cancer: A Real-World Cohort Study

Background: Rheumatic immune-related adverse events (R-irAEs) after immune checkpoint inhibitor (ICI) therapy in lung cancer can be difficult to distinguish from cancer-related or degenerative musculoskeletal symptoms. Methods: In this single-center retrospective cohort, we analyzed 768 ICI-treated patients and a nested questionnaire cohort to characterize rheumatologist-confirmed R-irAEs, baseline associated factors, and patient-reported outcomes. Missing baseline C-reactive protein (CRP) was handled using multiple imputation. Results: New musculoskeletal symptoms occurred in 177 patients (23.0%), and 66 patients (8.6%) had confirmed R-irAEs. The leading phenotypes were inflammatory arthritis (n = 22), inflammatory arthralgia (n = 15), and polymyalgia rheumatica-like syndrome (n = 13). In multivariable analysis, female sex (adjusted odds ratio [OR] 2.21, 95% confidence interval [CI] 1.31–3.74), baseline CRP > 10 mg/L (OR 2.08, 95% CI 1.14–3.81), and pre-existing autoimmune disease (OR 5.24, 95% CI 2.37–11.57) were associated with confirmed R-irAEs. Among 437 questionnaire responders, confirmed R-irAEs were associated with worse pain, morning stiffness, disability, fatigue, and health status than non-confirmed musculoskeletal symptoms (all Holm-adjusted p < 0.001). Conclusions: Confirmed R-irAEs affected a measurable minority of ICI-treated patients with lung cancer and were associated with worse post-treatment patient-reported outcomes. Because baseline patient-reported outcomes were unavailable, these findings should not be interpreted as R-irAE-attributable change.