Abstract
Over the last decades, the treatment of Graves disease has been limited to antithyroid drugs, radioactive iodine ablation or surgery. Especially in the paediatric age group, all three therapeutic options have their advantages and side effects.
Highlights
Graves’ hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive thyroid hormone
This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves’ hyperthyroidism
The demand for innovative therapeutic options has led to the emergence of novel approaches in the treatment of Graves’ hyperthyroidism, including biologic, small molecule, and peptide immunomodulation, several of which have translational potential into clinical practice in the near future
Summary
Rituximab (anti-CD20) Iscalimab (anti-CD40) Belimumab (anti-BAFF) Neonatal Fc receptor blockade K1-70 (Blocking TRAb) Small molecular TSHR antagonists Immunomodulatory TSHR peptides. The therapeutic effect of intravenous immunoglobins in several autoimmune diseases is mediated by functional Fc receptor blockade, but these novel FcRn therapeutics demonstrate increased receptor binding affinity, which results in efficacy at a much lower dose (less than 50 mg/kg vs 1-2 g/kg body weight) [66, 67] Both efgartigimod and rozanolixizumab caused a sustained reduction in circulating IgG levels of approximately 75% to 90%, both in preclinical studies of murine models of autoimmune disease (arthritis and encephalitis) [63, 68] and in healthy human subjects [64, 69]. A series of compounds that inhibit TSHR function as inverse agonists (inhibiting basal as well as agonist-induced signaling) have been developed; the best studied compound has been termed ANTAG-3 [17, 18] These compounds inhibit TSH-stimulated cAMP production in vitro and lower thyroid hormone levels in mice treated with the thyroidstimulating monoclonal antibody M22, suggesting likely efficacy in inhibiting TRAb-induced Graves’ hyperthyroidism.
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