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

      Pearce, S; Dayan, C; Wraith, D; Barrell, K; Olive, N; Jansson, L; Walker-Smith, T; Carnegie, C; Martin, K; Boelaert, K; et al. (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.
    • A follow-up study of the prevalence of valvular heart abnormalities in hyperprolactinemic patients treated with cabergoline.

      Drake, W; Stiles, C; Bevan, J; Karavitaki, N; Trainer, Peter J; Rees, D; Richardson, T; Baldeweg, S; Stojanovic, N; Murray, R; et al. (2016-08-29)
      CONTEXT Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease; and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate.