Objective
Immune checkpoint inhibitors (ICIs) improve overall survival (OS) and progression-free survival (PFS) in many types of malignancies but can result in off-target immune-related adverse events including inflammatory arthritis (ICI-associated inflammatory arthritis [ICI-IA]), which can persist even after ICI cessation. We aimed to examine the proportion of patients with ICI-IA who develop chronic ICI-IA and describe characteristics and outcomes associated with chronic ICI-IA.

Methods
We identified patients from the Canadian Research Group of Rheumatology in Immuno-Oncology retrospective cohort who developed de novo ICI-IA with at least three months of follow-up after ICI cessation. Chronic ICI-IA was defined as symptoms or ongoing immunosuppression lasting beyond three months after ICI discontinuation. Acute ICI-IA was defined as resolution of ICI-IA symptoms and discontinuation of immunosuppression within three months of ICI discontinuation. OS and PFS were assessed with Kaplan–Meier curves. Landmark multivariable Cox proportional hazard models for OS and PFS were conducted.

Results
The study cohort included 119 patients. A total of 15 patients (13%) had acute ICI-IA, whereas 104 (87%) had chronic ICI-IA. Patients with chronic ICI-IA were more likely to be White and to have polyarthritis at presentation. After adjusting for age, sex, tumor type, stage of cancer, ICI-IA treatment, and time from ICI initiation to ICI-IA onset, patients with chronic ICI-IA had greater PFS from ICI initiation (adjusted hazard ratio 0.27, 95% confidence interval 0.08–0.98; P = 0.046). Adjusted hazard ratio for OS was similar between those with acute versus chronic ICI-IA.

Conclusion
ICI-IA frequently persists after ICI discontinuation. Chronic ICI-IA is associated with improved PFS, but not OS, as compared to acute ICI-IA.

Alexandra Ladouceur, Shahin Jamal, Alexandra Saltman, Megan Himmel, Marie Hudson, Janet Pope, Sabrina Hoa, Janet Roberts, Inés Colmegna, Lourdes Gonzalez Arreola, Tatiana Nevskaya, Ammana Karmali, David Moon, Emma Schmidt, Nader Toban, Lindsay Cho, Thomas Barnetche, Carrie Ye