Marked and reversible circulating insulin-like growth factor-1 elevation during teprotumumab N01 treatment for...

Insulin-like growth factor-1 (IGF-1) receptor (IGF-1R) inhibitors have changed the treatment landscape for moderate-to-severe thyroid eye disease (TED), but the longitudinal behavior of circulating IGF-1 during and after therapy remains insufficiently characterized. This study aimed to describe serum IGF-1 dynamics in patients with TED treated with IGF-1R inhibitor teprotumumab N01 and to explore their relationship with glycemic changes.

In this retrospective cohort study, 92 patients with moderate-to-severe TED treated with teprotumumab N01 who had longitudinal IGF-1 measurements were included. IGF-1 dynamics were characterized at infusion-based visits and during post-treatment follow-up. Glycemic changes were assessed using fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and glycated albumin (GA). Patients were classified by baseline glycemic status. Associations between IGF-1 metrics and glycemic changes were evaluated using multivariable linear regression for continuous glycemic outcomes and logistic regression for threshold-defined glycemic events, with sequential adjustment for age, sex, baseline glycemic markers, and baseline IGF-1 when applicable. Additional analyses were performed according to baseline glycemic status and baseline HbA1c quartiles.

Baseline serum IGF-1 was 151.0 ng/mL (IQR 116.8-187.3). IGF-1 increased markedly after treatment initiation, with a median early-treatment peak fold change of 3.5 (IQR 3.0-4.3) and a median on-treatment peak concentration of 649.5 ng/mL (IQR 520.8-753.8), corresponding to a 4.2-fold increase from baseline (IQR 3.5-5.0). IGF-1 remained elevated during the first 3 months after the last infusion and then declined progressively, generally approaching baseline by 6-9 months or later. Glycemic markers showed modest increases, with median peak increases from baseline of 0.40% (IQR 0.20-0.77) for HbA1c, 1.63% (IQR 0.95-2.39) for GA, and 0.65 mmol/L (IQR 0.30-1.14) for FBG. Glycemic deterioration was most pronounced in patients with baseline dysglycemia. In contrast, neither baseline IGF-1 nor IGF-1 dynamic metrics were consistently identified as independent correlates of glycemic changes after adjustment for age, sex, and baseline glycemic markers and IGF-1. Similar findings were observed in subgroup and HbA1c quartile analyses.

Teprotumumab N01 treatment was associated with a substantial, early, and broadly reversible increase in circulating IGF-1 in patients with moderate-to-severe TED, but IGF-1 dynamics did not serve as an independent indicator of glycemic deterioration.