Chronicity of Immune Checkpoint Inhibitor-Associated Inflammatory Arthritis After Immunotherapy Discontinuation: Results From the Canadian Research Group of Rheumatology in Immuno-Oncology Database.

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.