Teprotumumab for the Treatment of Active Thyroid Eye Disease
In the current trial (OPTIC), researchers investigated the efficacy and safety of teprotumumab, an IGF-IR inhibitor, as compared with placebo in patients with clinically active thyroid eye disease.

Whereas the phase 2 trial evaluated proptosis as a component of the primary outcome, the OPTIC trial focused on clinically meaningful reductions in proptosis as the primary outcome.

The outcomes were better among those who received teprotumumab than among those who received placebo, with meaningful between-group differences in proptosis response, Clinical Activity Score, diplopia response, & overall response.

The effect of teprotumumab was rapid for each outcome, which was evident at the first postbaseline assessment at week 6, and the outcomes continued to improve over the 24-week treatment period.

Teprotumumab, a fully human monoclonal antibody, attenuates signaling initiated at either receptor, thereby blocking pathologic immune responses in active thyroid eye disease.

In this phase 3 multicenter trial, researchers assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks.

The primary outcome was a proptosis response (a reduction in proptosis of more than 2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of more than 2 points in the Clinical Activity Score plus a reduction in proptosis of more than 2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of more than 1 grade), and the mean change in overall score on the Graves’ ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of more than 6 points is considered clinically meaningful).

A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P less than 0.001),

Conclusively, among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1910434?query=RES
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