Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase I study

Simon H S Pearce, Colin Dayan, David C Wraith, Kevin Barrell, Natalie Olive, Lotta Jansson, Terrie Walker-Smith, Christina Carnegie, Keith F Martin, Kristien Boelaert, Jackie Gilbert, Claire E Higham, Ilaria Muller, Robert D Murray, Petros Perros, Salman Razvi, Bijay Vaidya, Florian Wernig, George J Kahaly

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)1003-1011
Number of pages9
JournalThyroid
Volume29
Issue number7
Early online date13 Jun 2019
DOIs
Publication statusPublished - 17 Jul 2019

Keywords

  • peptide immunotherapy
  • Graves’ disease
  • autoimmune thyroid disease
  • desensitization
  • thyroid stimulating hormone receptor
  • immunomodulation

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