Teprotumumab for the Treatment of Thyroid Eye Disease.

Abstract

Thyroid eye disease (TED) is the most common extra thyroidal manifestation of Graves' disease (GD). It may also present in those who are hypothyroid or euthyroid. The characteristic clinical manifestations of TED, chemosis, lid swelling, proptosis, and diplopia, are driven by a combination of inflammation and extracellular matrix modification. It has recently emerged that 1 of the major drivers of this molecular signature is the overexpression of the IGF-1 receptor [IGF-1R]) on key effector cells in TED pathogenesis. The overexpression of the IGF-1R is coupled with a dysregulation of the IGF-1R axis, which links other pathways that modulate inflammation, such as fibrosis and extracellular matrix organization, in patients with TED. This overexpression is also found to persist from the acute stage into the chronic phase. Teprotumumab, a fully human IgG1 monoclonal antibody that inhibits the IGF-1R, recently gained approval in the United States for the treatment of TED. In phase 2 and phase 3 clinical studies, teprotumumab showed efficacy in reducing inflammation, proptosis, diplopia, and burden on quality of life in patients who were treated. Postintroduction studies have confirmed the results of the phase 2 and phase 3 studies. Since 2020, more than 5800 patients have been treated with teprotumumab, and it appears to be well tolerated. The American Thyroid Association and the European Thyroid Association have recommended it as first-line therapy for patients with moderate to severe TED who display features of proptosis and diplopia.