Introduction:
Thyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). In contrast to other autoimmune diseases and irAE, a history of thyroid dysfunction generally does not preclude administration of ICI, and thyroid irAE are not usually treated with ICI interruption or immunosuppression. We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI.
Methods:
We included all patients treated with ICI at UT Southwestern Medical Center, Dallas, Texas, USA from January 1, 2011, through December 31, 2020. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were defined according to institutional reference range. We defined clinical thyroid dysfunction using established criteria incorporating labs, symptoms, and treatment. We determined the association between thyroid function and overall survival (OS) using Kaplan-Meier curves, log-rank tests, and multivariate Cox proportional hazards model.
Results:
A total of 1,781 patients were included, of whom 381 (21%) had abnormal baseline TSH. Patients with abnormal baseline TSH were more likely to be female and have kidney cancer (all P<0.001). Patients with abnormal baseline TSH had inferior OS (median 16 vs 26 months; P<0.001). Among patients with normal baseline TSH, those who had abnormal TSH after ICI initiation had improved OS (median 41 vs 21 months; P<0.001). In a multivariate Cox model, abnormal baseline TSH was associated with worse OS (HR 1.52; 95% CI, 1.23-1.89; P<0.001), while initiation of levothyroxine after ICI initiation was associated with improved OS (HR 0.64; 95% CI, 0.47-0.88; P=0.006).
Conclusions:
ICI-induced thyroid dysfunction is associated with improved survival. However, abnormal TSH prior to ICI initiation is associated with inferior survival. Potential biologic explanations for these discrepant effects merit investigation.