Association of anti-thyroid antibodies in checkpoint inhibitor associated thyroid immune related adverse events

Abstract Objective The significance of thyroid peroxidase (TPOAb) and thyroglobulin antibody (TgAb) in the pathogenesis of thyroid immune-related adverse events (irAEs) is unknown. Methods Retrospective cohort study of patients with melanoma receiving immune checkpoint inhibitor (ICI) treatment. TPOAb, TgAb and interleukin-6 (IL-6) were measured retrospectively using tumor-banked samples at baseline and at time of diagnosis of a thyroid irAE. In euthyroid patients (without thyroid irAEs) measures were repeated 30-60 days after ICI-commencement, which was similar to the median time to onset of thyroid irAEs in other patients. Results 122 patients were included – 31 remained euthyroid, 47 developed subclinical thyrotoxicosis, 37 developed overt thyrotoxicosis and 7 developed overt hypothyroidism without preceding thyrotoxicosis. Baseline elevation of TPOAb or TgAb was present in 19 (16%) and 28 (23%) of patients, respectively. Positive TPOAb or TgAb at baseline was 97% and 100% specific for eventual development of a thyroid irAE, respectively. During ICI-treatment, overt thyrotoxicosis, but not other subtypes of thyroid irAE was associated with significant increases in the titre of TgAb and TPOAb. Baseline IL-6 levels were not associated with thyroid irAE onset but significantly increased during treatment in patients who developed overt hypothyroidism. Conclusions TPOAb and TgAb positivity at baseline was more prevalent in patients who developed thyroid irAEs. Significant increases or new antibody positivity was observed in association with overt thyrotoxicosis. TPOAb and TgAb positivity or increases during ICI-treatment may be a useful biomarker to identify patients at increased risk of thyroid irAEs, particularly overt thyrotoxicosis.