Case-control study identifying predictors of rheumatic toxicities and ICI-inflammatory arthritis.

Citation: Cunningham-Bussel A, Wang J, Prisco LC, Martin LW, Vanni KMM, Zaccardelli A, Nasrallah M, Gedmintas L, MacFarlane LA, Shadick NA, Awad MM, Rahma O, LeBoeuf NR, Gravallese EM, Sparks JA. Predictors of rheumatic immune-related adverse events and de novo inflammatory arthritis after immune checkpoint inhibitor treatment for cancer. Arthritis Rheumatol. 2021 Aug 16. doi: 10.1002/art.41949. Epub ahead of print. PMID: 34397169.

ABSTRACT
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.