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Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study
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' hyperthyro...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc., publishers
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648194/ https://www.ncbi.nlm.nih.gov/pubmed/31194638 http://dx.doi.org/10.1089/thy.2019.0036 |
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author | Pearce, Simon H.S. Dayan, Colin Wraith, David C. Barrell, Kevin Olive, Natalie Jansson, Lotta Walker-Smith, Terrie Carnegie, Christina Martin, Keith F. Boelaert, Kristien Gilbert, Jackie Higham, Claire E. Muller, Ilaria Murray, Robert D. Perros, Petros Razvi, Salman Vaidya, Bijay Wernig, Florian Kahaly, George J. |
author_facet | Pearce, Simon H.S. Dayan, Colin Wraith, David C. Barrell, Kevin Olive, Natalie Jansson, Lotta Walker-Smith, Terrie Carnegie, Christina Martin, Keith F. Boelaert, Kristien Gilbert, Jackie Higham, Claire E. Muller, Ilaria Murray, Robert D. Perros, Petros Razvi, Salman Vaidya, Bijay Wernig, Florian Kahaly, George J. |
author_sort | Pearce, Simon H.S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6648194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Mary Ann Liebert, Inc., publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-66481942019-07-23 Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study Pearce, Simon H.S. Dayan, Colin Wraith, David C. Barrell, Kevin Olive, Natalie Jansson, Lotta Walker-Smith, Terrie Carnegie, Christina Martin, Keith F. Boelaert, Kristien Gilbert, Jackie Higham, Claire E. Muller, Ilaria Murray, Robert D. Perros, Petros Razvi, Salman Vaidya, Bijay Wernig, Florian Kahaly, George J. Thyroid Immunology, Autoimmunity, and Graves’ Ophthalmopathy 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. Mary Ann Liebert, Inc., publishers 2019-07-01 2019-07-17 /pmc/articles/PMC6648194/ /pubmed/31194638 http://dx.doi.org/10.1089/thy.2019.0036 Text en © Simon H.S. Pearce et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Immunology, Autoimmunity, and Graves’ Ophthalmopathy Pearce, Simon H.S. Dayan, Colin Wraith, David C. Barrell, Kevin Olive, Natalie Jansson, Lotta Walker-Smith, Terrie Carnegie, Christina Martin, Keith F. Boelaert, Kristien Gilbert, Jackie Higham, Claire E. Muller, Ilaria Murray, Robert D. Perros, Petros Razvi, Salman Vaidya, Bijay Wernig, Florian Kahaly, George J. Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study |
title | Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study |
title_full | Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study |
title_fullStr | Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study |
title_full_unstemmed | Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study |
title_short | Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study |
title_sort | antigen-specific immunotherapy with thyrotropin receptor peptides in graves' hyperthyroidism: a phase i study |
topic | Immunology, Autoimmunity, and Graves’ Ophthalmopathy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648194/ https://www.ncbi.nlm.nih.gov/pubmed/31194638 http://dx.doi.org/10.1089/thy.2019.0036 |
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