Clinical Study

Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study

Abstract

Background

Anti-programmed cell death-1 (PD-1) antibodies can cause thyroid dysfunction. However, no predictive biomarkers enabling stratification of thyroid dysfunction risk have been identified.

Methods

A total of 209 patients treated with an anti-PD-1 antibody were evaluated for anti-thyroid antibodies at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the visits stopped. Thyroid ultrasonography was performed if the patient was positive for anti-thyroid antibodies at baseline.

Results

Of the 209 patients, 19 (9.1%) developed thyroid dysfunction (destructive thyroiditis or hypothyroidism). The cumulative incidence of thyroid dysfunction was significantly higher in patients who were positive vs. negative for anti-thyroid antibodies (15/44 [34.1%] vs. 4/165 [2.4%], p < 0.001). Forty-two patients positive for anti-thyroid antibodies at baseline were divided into two groups according to the presence of an irregular echo pattern. The cumulative incidence of thyroid dysfunction was significantly higher in those with an irregular vs. a regular echo pattern (13/23 [56.5%] vs. 1/19 [5.3%], p = 0.001). None of the patients developed thyroid dysfunction after the initial 24-week period.

Conclusions

The risk of thyroid dysfunction induced by anti-PD-1 antibodies can be predicted by evaluation of anti-thyroid antibodies and the thyroid echo pattern at baseline.

Trial registration

UMIN000019024.

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Fig. 1: Flow diagram of the patients included in this study.
Fig. 2: The presence of anti-thyroid antibodies at baseline was associated with the development of destructive thyroiditis and/or hypothyroidism in patients treated with anti-PD-1 antibodies.
Fig. 3: An irregular echo pattern was associated with the development of destructive thyroiditis and/or hypothyroidism in patients treated with anti-PD-1 antibodies.

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Affiliations

Authors

Contributions

S.I. designed the study. N.O., T.K. and S.I. performed the clinical study. N.O., S.I. and H.A. analysed the data. N.O., S.I. and H.A. wrote the paper. N.O., S.I., T.Ok., T.K., Y.Y., E.W., T.On., Mot.G., M.S., T.T., H.T., D.H., Y.I., H.S., R.B., T.H., M.M., M.K., K.Y., N.H., M.An., Y.F., M.N., Y.K., M.F., H.H., M.S., H.K., Mom.G., Y.A., M.Ak., Y.H. and H.A. recruited and treated the patients, collected and discussed the data and helped revise the paper. All authors reviewed and approved the final paper.

Corresponding author

Correspondence to Shintaro Iwama.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethical Committee of Nagoya University Hospital (approval number: 2015-0273), and was performed in accordance with the Declaration of Helsinki. All enrolled patients provided written informed consent before any of the study-specific procedures were performed. Clinical trial information: www.umin.ac.jp no. UMIN000019024 (registered September 15, 2015).

Consent to publish

We obtained consent for publication from all patients in this study.

Data availability

All data included in this study are available upon request, sent to the corresponding author.

Competing interests

S.I. is a consultant/advisory board member for endocrinological adverse events at Ono Pharmaceutical Company and Bristol-Myers Squibb, and receives fees for presentations, consulting and advising, and the writing of published materials from Ono Pharmaceutical Company, Bristol-Myers Squibb and MSD K.K. T.H. receives personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb and MSD K.K. M.M. receives personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb and MSD K.K. M.N. receives a grant from Bristol-Myers Squibb. Y.K. receives grants and personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb and MSD K.K. M.F. receives personal fees from Ono Pharmaceutical Company, and MSD K.K. H.K. receives grants and personal fees from Ono Pharmaceutical Company and Bristol-Myers Squibb, and MSD K.K. M.G. receives grants from Ono Pharmaceutical Company. Y.A. receives grants from Ono Pharmaceutical Company and personal fees from Ono Pharmaceutical Company and Bristol-Myers Squibb. M.Ak. receives grants from Ono Pharmaceutical Company, and MSD K.K. Y.H. receives grants and personal fees from Ono Pharmaceutical Company and Bristol-Myers Squibb, and MSD K.K. H.A. receives grants from Ono Pharmaceutical Company. MSD K.K. receives personal fees from Ono Pharmaceutical Company and Bristol-Myers Squibb. The remaining authors have nothing to disclose.

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The authors declare no funding support.

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Okada, N., Iwama, S., Okuji, T. et al. Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study. Br J Cancer 122, 771–777 (2020). https://doi.org/10.1038/s41416-020-0736-7

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