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Thyroid

(16.04) Hyperglycemia in Patients Treated with Teprotumumab for Long Duration, Low Inflammation Thyroid Eye Disease (TED)

Friday, May 10, 2024
3:05 PM – 3:20 PM CDT
Location: ePoster Showcase, Empire Ballroom Foyer, Level 2

    Submitter(s)

  • EC

    Elizabeth Conrad, PhD

    Senior Manager, Publications and Data Management
    Amgen Inc
    Thousand Oaks, California, United States

    • Presenter(s)

  • Terry J. Smith, MD

    Frederick G.L. Huetwell Professor Emeritus of Ophthalmology and Visual Sciences Professor Emeritus of Internal Medicine
    University of Michigan Kellogg Eye Center
    Ann Arbor, Michigan, United States

Objective :

Teprotumumab, an insulin-like growth factor-I receptor inhibitor, improved proptosis and quality of life related to visual function in the first placebo-controlled trial in patients with TED duration 2-10 years and clinical activity score ≤1.1 Hyperglycemia was reported in 6/42 (14.6%) teprotumumab-treated patients and in 2/20 (10%) placebo-treated patients.1 Here, we report serum glucose and glycated hemoglobin A1c (HbA1c) results from that trial.

Methods: Glycemic data from the randomized, double-masked, placebo-controlled trial were analyzed. Fasting blood glucose was measured at baseline, Weeks 6, 12, 18, 24; HbA1c was required to be ≤8% at baseline. HbA1c was measured at baseline, Weeks 12 and 24 (normal: 4-5.6%; high: >5.6%2).

Results:

Mean (SD) baseline fasting blood glucose in teprotumumab patients was 4.96 (0.5) versus 5.02 (1.1) mmol/L in placebo. At Week 24, mean fasting blood glucose increased from baseline in teprotumumab patients by 0.52 mmol/L (~10%) and 0.02 mmol/L (~0.4%) in placebo patients. At baseline, mean (SD) HbA1c was 5.49 (0.37) % in teprotumumab and 5.51 (0.64) % in placebo. At Week 24, mean change from baseline was 0.41% and -0.08%, respectively.

28/41 (68%) teprotumumab patients had normal baseline HbA1c; at Week 24, 20 remained normal, 7 were high and 1 value was missing. 12 patients with high baseline HbA1c remained high at Week 24, 1 with a high baseline value had a missing Week 24 value. 14/20 (70%) placebo patients had normal HbA1c at both baseline and Week 24, 1 with high baseline had normal HbA1c at Week 24, and 5 had high HbA1c at baseline and Week 24.

Eight hyperglycemia adverse events (AEs) were reported in 6 (15%) teprotumumab patients; 1 had pre-existing diabetes, 4 patients had preexisting pre-diabetes (HbA1c 5.7-6.4%)2 and 1 was normoglycemic. During the trial, 3 patients had increased HbA1c ( >5.6%), 2 reported diabetes mellitus, 2 had hyperglycemia and 1 impaired glucose tolerance. All events were Grade 1 (mild, CTCAE), and none led to study drug discontinuation.

Three AEs were reported in 2 placebo patients, including one patient with undiagnosed, uncontrolled diabetes at baseline who experienced a serious event (diabetic ketoacidosis, DKA) after erroneously receiving one dose of teprotumumab.1 The event resolved with treatment and the patient completed the trial.

Discussion/Conclusion:

A majority of teprotumumab patients with hyperglycemia had either pre-existing diabetes or pre-diabetes at baseline. AEs in the teprotumumab group were mild, not leading to discontinuation. AEs were consistent with observations in the phase 2 and 3 teprotumumab trials.  

References
1. Douglas RS, et al. J Clin Endocrinol Metab. 2023 Oct 31:dgad637. doi: 10.1210/clinem/dgad637.
2. American Diabetes Association. 2019. Diabetes Care 2019;42(Suppl. 1):S13–S28.