Abstract
Abstract:
Graves’ Disease (GD) is the leading cause of autoimmune hyperthyroidism and is still considered a
challenging clinical condition. Antithyroid drugs, radioactive iodine, and thyroidectomy have long been used
as main treatments. These approaches are generally effective in restoring euthyroidism and controlling thyroid
function, even if they cannot target the underlying autoimmune mechanisms implicated in the disease. As a
result, relapses after medical therapy remain frequent, whereas definitive treatments often lead to permanent
hypothyroidism and the need for a lifelong thyroid hormone replacement. New results in the study of immunological
mechanisms underlying GD have led to the development of targeted therapies. Targeted strategies
are based on key components of disease pathogenesis, such as the thyrotropin receptor, B lymphocytes,
co-stimulatory immune pathways, the insulin-like growth factor-1 receptor, and neonatal Fc receptors. A
pivotal step in the development of targeted mechanism-based therapies for GD has been reached with the
approval of teprotumumab. Several targeted therapies have been evaluated, such as K1-70, iscalimab,
rituximab, tocilizumab, batoclimab, and the antigen-specific immunotherapy ATX-GD-59. This review
highlights the limitations of currently available treatment options by examining the most promising emerging
therapies and the future horizons for precision medicine in GD. Advances in the therapeutic landscape offer
disease-modifying strategies that could complement and potentially replace current treatment strategies.