Effect of Age on Rheumatic Immune-Related Adverse Events: Experience From the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO)

Objective Immune checkpoint inhibitors (ICIs) have revolutionized cancer outcomes but are limited by immune-related adverse events (irAEs), including rheumatic irAEs (Rh-irAEs). Aging is associated with increased inflammation, referred to as “inflammaging.” In this study, we explore the effect of age on severity, frequency, and treatment of Rh-irAEs.

Methods Adults with new Rh-irAEs after ICI exposure are followed prospectively across 10 Canadian sites as part of the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) prospective cohort. In this study of patients seen between January 2020 and March 2023, we compare the severity of Rh-irAEs and number of irAEs between patients aged ≥ 65 years and < 65 years and explore potential epidemiologic, treatment-related, and phenotypic differences between the older and younger patients.

Results A total of 139 patients with de novo Rh-irAEs were included, 58 in the younger (aged < 65 yrs) and 81 in the older (aged ≥ 65 yrs) group. There were no significant differences in severity of Rh-irAEs (P = 0.84) or number of irAEs (P = 0.21), although there was a nonsignificant trend toward more younger patients than older patients with ≥ 3 irAEs (24% vs 14%). Types of treatment for Rh-irAEs were similar between the groups. ICI continuation did not differ. Within the ICI-related inflammatory arthritis subgroup, there was also no significant difference in the incidence of severe Rh-irAEs (P = 0.51).

Conclusion Similar numbers of overall irAEs and severity of Rh-irAEs were observed between older vs younger patients who developed Rh-irAEs after treatment with ICI therapy, suggesting that inflammaging does not play a significant role in Rh-irAEs. Larger studies are needed to explore potential differences in patient phenotypes.