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

Research output: Contribution to journalArticle

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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.

In: Thyroid, Vol. 29, No. 7, 17.07.2019, p. 1003-1011.

Research output: Contribution to journalArticle

Harvard

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 2019, 'Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase I study', Thyroid, vol. 29, no. 7, pp. 1003-1011. https://doi.org/10.1089/thy.2019.0036

APA

Pearce, S. H. S., Dayan, C., Wraith, D. C., Barrell, K., Olive, N., Jansson, L., Walker-Smith, T., Carnegie, C., Martin, K. F., Boelaert, K., Gilbert, J., Higham, C. E., Muller, I., Murray, R. D., Perros, P., Razvi, S., Vaidya, B., Wernig, F., & Kahaly, G. J. (2019). Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase I study. Thyroid, 29(7), 1003-1011. https://doi.org/10.1089/thy.2019.0036

Vancouver

Pearce SHS, Dayan C, Wraith DC, Barrell K, Olive N, Jansson L et al. Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase I study. Thyroid. 2019 Jul 17;29(7):1003-1011. https://doi.org/10.1089/thy.2019.0036

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. / Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism : a phase I study. In: Thyroid. 2019 ; Vol. 29, No. 7. pp. 1003-1011.

Bibtex

@article{923da8287d3e41b89da20ea5045cd1ec,
title = "Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism: a phase I study",
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.",
keywords = "peptide immunotherapy, Graves{\textquoteright} disease, autoimmune thyroid disease, desensitization, thyroid stimulating hormone receptor, immunomodulation",
author = "Pearce, {Simon H S} and Colin Dayan and Wraith, {David C} and Kevin Barrell and Natalie Olive and Lotta Jansson and Terrie Walker-Smith and Christina Carnegie and Martin, {Keith F} and Kristien Boelaert and Jackie Gilbert and Higham, {Claire E} and Ilaria Muller and Murray, {Robert D} and Petros Perros and Salman Razvi and Bijay Vaidya and Florian Wernig and Kahaly, {George J}",
year = "2019",
month = jul,
day = "17",
doi = "10.1089/thy.2019.0036",
language = "English",
volume = "29",
pages = "1003--1011",
journal = "Thyroid",
issn = "1050-7256",
publisher = "Mary Ann Liebert",
number = "7",

}

RIS

TY - JOUR

T1 - Antigen-specific immunotherapy with thyrotropin receptor peptides in Graves' hyperthyroidism

T2 - a phase I study

AU - Pearce, Simon H S

AU - Dayan, Colin

AU - Wraith, David C

AU - Barrell, Kevin

AU - Olive, Natalie

AU - Jansson, Lotta

AU - Walker-Smith, Terrie

AU - Carnegie, Christina

AU - Martin, Keith F

AU - Boelaert, Kristien

AU - Gilbert, Jackie

AU - Higham, Claire E

AU - Muller, Ilaria

AU - Murray, Robert D

AU - Perros, Petros

AU - Razvi, Salman

AU - Vaidya, Bijay

AU - Wernig, Florian

AU - Kahaly, George J

PY - 2019/7/17

Y1 - 2019/7/17

N2 - 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.

AB - 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.

KW - peptide immunotherapy

KW - Graves’ disease

KW - autoimmune thyroid disease

KW - desensitization

KW - thyroid stimulating hormone receptor

KW - immunomodulation

U2 - 10.1089/thy.2019.0036

DO - 10.1089/thy.2019.0036

M3 - Article

C2 - 31194638

VL - 29

SP - 1003

EP - 1011

JO - Thyroid

JF - Thyroid

SN - 1050-7256

IS - 7

ER -