Immune Checkpoint Inhibitor-related New-onset Thyroid Dysfunction: A Retrospective Analysis Using the US FDA Adverse Event Reporting System

Immune checkpoint inhibitors (ICIs) have emerged as a remarkable therapeutic option for patients with advanced cancer; however, thyroid dysfunction is a common ICI-related adverse event. This article reports on the prevalence and demographic characteristics of ICI-related thyroid dysfunction and explores risk factors of poor clinical outcome using data from the US FDA Adverse Event Reporting System. Objectives The study aimed to investigate the prevalence and demographic characteristics of an immune checkpoint inhibitor (ICI)-related thyroid dysfunction (ICI-TD), and to explore risk factors of poor clinical outcome using data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods This is a retrospective study. All cases, aged over 18-year olds, of new-onset or new-diagnosed thyroid dysfunction related to FDA-approved ICIs from January 1, 2011 to December 31, 2020 were identified using FAERS. Data of age, gender, other combined endocrinopathies related to ICIs besides ICI-TDs, and the prognosis was analyzed. Results In total, 2.60% (2971/114 121) cases of ICI-TDs were identified. Among them, 1842 (62.0%) developed hypothyroidism, 675 (22.7%) were hyperthyroidism, and 454 (15.3%) presented in thyroiditis without the mention of thyroid function. Patients on anti- programmed cell death protein-1 (PD-1) therapy displayed higher risk of hypothyroidism compared with other 3 regimens, respectively (P < .01 for all). The likelihood of other immune-related endocrinopathies in patients on the combination therapy of anti-cytotoxic T-cell-associated protein-4 (CTLA-4) and anti-PD-1 was significantly elevated than anti-PD-1 (odds ratio [OR] 2.362, 95% confidence interval [CI] [1.925-2.898], P < .001) and anti-programmed death-ligand 1 (PD-L1) regimens (OR 4.857, 95%CI [3.228-7.308], P < .001). The risk of severe cases was positively related to hypothyroidism in individuals on anti-PD-1 therapy (OR 1.587, 95%CI [1.146-2.197], P = .005) and those on anti-CTLA-4 therapy (OR 3.616, 95%CI [1.285-10.171], P = .015). The risk of severe cases was positively associated with the comorbidity with other endocrinopathies (anti-PD-1 group, OR 0.285, 95%CI [0.200-0.467], P < .001; anti-PD-1+anti-CTLA-4 group, OR 0.574, 95%CI [0.371-0.890], P = .013). Conclusions Regular monitor of thyroid function is indispensable, since ICI-TDs manifested as hypothyroidism or hyperthyroidism, especially those on the combination therapy. Awareness among health care professionals is critical when hypothyroidism occurs, which might indicate poor clinical outcomes.

Automated summary

This article investigates the prevalence and demographic characteristics of immune checkpoint inhibitor (ICI)-related thyroid dysfunction (ICI-TD) and explores the risk factors of poor clinical outcomes. It finds that thyroid dysfunction is common in ICI treatment, especially in combination therapy.