Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase I study
Research output: Contribution to journal › Article
- Institute for Genetic Medicine, Newcastle University, and Newcastle Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.
- Thyroid Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom.
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham United Kingdom.
- Apitope Technology (Bristol) Ltd., Chepstow, United Kingdom.
- Apitope International NV, Diepenbeek, Belgium.
- Department of Endocrinology, King's College Hospital, London, United Kingdom.
- Department of Endocrinology, Christie Hospital NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
- Department of Endocrinology, St. James's University Hospital, Leeds, United Kingdom.
- Endocrine Unit, Newcastle Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.
- Institute for Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
- Macleod Diabetes & Endocrine Centre, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
- Department of Endocrinology, Imperial College, London, United Kingdom.
- Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany.
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham United Kingdom.
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.
|Number of pages||9|
|Early online date||13 Jun 2019|
|Publication status||Published - 17 Jul 2019|
- peptide immunotherapy, Graves’ disease, autoimmune thyroid disease, desensitization, thyroid stimulating hormone receptor, immunomodulation