Lookup NU author(s): Professor Simon Pearce,
Dr Petros Perros,
Dr Salman Razvi
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Simon H.S. Pearce et al. 2019; Published by Mary Ann Liebert, Inc. 2019.Background: Graves' disease is one of the most common autoimmune conditions, but treatment remains imperfect. This study explores the first-in-human use of antigen-specific immunotherapy with a combination of two thyrotropin receptor (TSHR) peptides (termed ATX-GD-59) in Graves' hyperthyroidism. Methods: Twelve participants (11 female) with previously untreated mild to moderate Graves' hyperthyroidism were enrolled in a Phase I open label trial to receive 10 doses of ATX-GD-59 administered intradermally over an 18-week period. Adverse events, tolerability, changes in serum free thyroid hormones, and TSHR autoantibodies were measured. Results: Ten subjects received all 10 doses of ATX-GD-59, five (50%) of whom had free triiodothyronine within the reference interval by the 18-week visit. Two further subjects had improved free thyroid hormones by the end of the study (7/10 responders), whereas three subjects showed worsening thyrotoxicosis during the study. Serum TSHR autoantibody concentrations reduced during the study and correlated with changes in free thyroid hormones (r = 0.85, p = 0.002 for TSHR autoantibody vs. free triiodothyronine). Mild injection-site swelling and pain were the most common adverse events. Conclusions: These preliminary data suggest that ATX-GD-59 is a safe and well-tolerated treatment. The improvement in free thyroid hormones in 70% of subjects receiving the medication suggests potential efficacy as a novel treatment for Graves' hyperthyroidism.
Author(s): Pearce SHS, Dayan C, Wraith DC, Barrell K, Olive N, Jansson L, Walker-Smith T, Carnegie C, Martin KF, Boelaert K, Gilbert J, Higham CE, Muller I, Murray RD, Perros P, Razvi S, Vaidya B, Wernig F, Kahaly GJ
Publication type: Article
Publication status: Published
Print publication date: 17/07/2019
Online publication date: 13/06/2019
Acceptance date: 02/04/2016
Date deposited: 29/07/2019
ISSN (print): 1050-7256
ISSN (electronic): 1557-9077
Publisher: Mary Ann Liebert Inc.
PubMed id: 31194638
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