Predictors of rheumatic immune-related adverse events and de novo inflammatory arthritis after immune checkpoint inhibitor treatment for cancer

Objective To identify predictors of rheumatic immune-related adverse events (rheum-irAEs) after immune checkpoint inhibitor (ICI) treatment for cancer. Methods We performed a case-control study to predict rheum-irAEs at Mass General Brigham and Dana-Farber Cancer Institute (2011-2020). We screened for rheum-irAEs by reviewing patients evaluated by rheumatology or prescribed non-glucocorticoid immunomodulators (IM) after ICI (baseline). Medical review confirmed the presence of rheum-irAEs and indication for IM. Controls lacked rheum-irAEs (had no glucocorticoid use, rheumatology evaluation, IM use, and survived 6 months after baseline). We used logistic regression to estimate odds ratios (ORs) of the baseline predictors of rheum-irAEs. Results We identified 8,028 ICI recipients (mean age 65.5 years, 43.1% female, and 31.8% with lung cancer). After ICI, 404 (5.0%) were evaluated by rheumatology and 475 (5.9%) received an IM to treat any irAE. There were 226 (2.8%) confirmed rheum-irAE cases and 118 (1.5%) had de novo inflammatory arthritis. Rheumatic diseases (either pre-existing or rheum-irAEs) were a leading indication for IM use (27.9%). Baseline predictors of rheum-irAEs included melanoma (multivariable OR 4.06, 2.54-6.51) and genitourinary cancer (OR 2.22, 1.39-3.54; ref=lung cancer), combination ICI (OR 2.35, 1.48-3.74; ref=PD-1 inhibitor monotherapy), autoimmune disease (OR 2.04, 1.45-2.85), and recent glucocorticoid use (OR 2.13, 1.51-2.98; ref=no use) compared to 2,312 controls without rheum-irAEs. Predictors of de novo inflammatory arthritis were similar. Conclusion We identified novel predictors of rheum-irAEs that included melanoma, genitourinary cancer, pre-existing autoimmune disease, combination ICI, and glucocorticoid use. The proportion of cancer patients experiencing rheum-irAEs may be even higher than we report since we used stringent criteria to identify cases. These findings may identify cancer patients at risk of developing rheum-irAEs and de novo inflammatory arthritis and inform pathogenesis.