Background/Purpose: The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy; however, their use can lead to off-target toxicities called immune-related adverse events (irAEs) that closely resemble primary autoimmune disease. Our study aimed to better understand the association between autoantibody positivity and irAE development.

Methods: Patients with cancer who were treated with ICIs from 1/1/2011 to 12/21/2020 and had a rheumatic autoantibody checked were retrospectively identified. Rheumatic autoantibodies evaluation in our study focused on the following serologies: Antinuclear antibody (ANA), Rheumatoid factor (RF), Cyclic citrullinated protein (CCP), but also included analysis of other serologies (anti–Sjögren’s-syndrome-related antigen A and B autoantibodies (SSA, SSB), double-stranded DNA, antineutrophil cytoplastic antibodies, angiotensin converting enzyme). Logistic regression model was used to evaluate the relationship between autoantibody analysis and irAE development as well as cancer outcome. Specificity, sensitivity and predictive values were also estimated. Cancer outcome was defined by objective response rate (ORR).

Results: 152 total patients were identified for review. Demographics are as noted in table 1. Of the patients who had rheumatic autoantibodies ordered, 90 (59%) were found to have irAE development. After adjusting for age at cancer diagnosis, sex, race, diagnosis of malignancy, and ICI group, patients with pre-ICI autoantibody positivity had greater odds of irAE development (OR 17.5, 95% CI 1.76-174.10, p=0.015). Development of irAE was associated with a 3.43 greater odds of an ORR for primary malignancy (95%CI: 1.35-8.72, p=0.01). There was no significant association with post-ICI autoantibody testing and any-type irAEs and the sensitivity, specificity, positive predictive value, and negative predictive value of any autoantibody positivity in development of irAEs were as follows: 63%, 30%, 56%, and 37% respectively. Subgroup analysis of rheumatic irAEs revealed a strong association between RF and CCP; for ICI-arthritis, RF showed sensitivity=0.24 and specificity=0.90 while CCP showed sensitivity=0.10 and specificity=0.98. Negative predictive values of RF and CCP for development of ICI-arthritis were 0.84 and 0.82 respectively.

Conclusion: Our results demonstrate strong association with pre-ICI autoantibody positivity and any-type irAE development as well as high specificity of RF and CCP for ICI-arthritis. Our findings justify prospective evaluation of rheumatic serologies and association with irAE development.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-rheumatic-autoantibody-positivity-and-immune-related-adverse-events/