Immune checkpoint inhibitors (ICIs) enhance survival outcomes for many patients with cancer but are associated with potential toxicities that can affect any organ system. Their side effects, called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. Therefore, researchers set out to investigate the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs. Their findings were published in The Oncologist.

For this study, 135 patients without preexisting autoimmune disease (pAID) who had cancer treated with ICI therapy between 2011 and 2020 and had at least 1 rhAb checked were retrospectively identified. Logistic regression was used to assess associations between autoantibodies and irAEs, cancer outcome, and survival. The researchers then estimated specificity, sensitivity, and positive/negative predictive values for key rhAbs and ICI-arthritis.

A significant association was noted between pre-ICI rheumatoid factor (RF) positivity and higher odds of developing rheumatic-irAEs. Findings also showed a correlation between rheumatic irAEs and ICI-arthritis and better overall survival.

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Explicit inquiry about inflammatory joint pain is recommended when reviewing patients’ symptoms before starting ICI therapy, rather than indiscriminately testing for autoantibodies prior to ICI initiation. However, a low threshold is recommended when considering consulting a rheumatologist if symptoms raise concerns about preexisting rheumatic disease.

“Our study underscores the potential relevance of pre-ICI serologic testing and provides certain clinical guidance for diagnosis of ICI-arthritis,” the research team concluded. “Our findings reinforce the importance of earlier subspecialty referrals to rheumatology in context of joint symptoms prior to ICI initiation and emphasize the need for higher vigilance for development of rheumatic-irAEs with pre-ICI RF positivity.”

The study did have some limitations. Its retrospective design with a lack of patient randomization may have allowed for potential unrecognized confounders. Practitioners would have been able to see serologic results at the time of clinical assessment, so there could be some practitioner bias in the diagnosis of rh-irAEs. Additionally, patients who were included in this study had a clinical reason to have their autoantibodies checked, so there may have been a higher pretest probability of autoantibody positivity than there would be in a general population of patients undergoing ICI treatment.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Mathias K, Rouhani S, Olson D, Bass AR, Gajewski TF, Reid P. Association between rheumatic autoantibodies and immune-related adverse events. Oncologist. Published online January 3, 2023. doi:10.1093/oncolo/oyac252