Endocrine Abstracts

Introduction: The initial clinical trials for teprotumumab excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose > 1gm), or biologic treatment. Therefore, information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED.

Methods: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥ 2mm reduction in the study eye without a similar increase in the other eye), Clinical Activity Score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥ 1 point improvement on the Gorman diplopia score (GDS)) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated.

Results: Sixty-seven patients were included in this study, 47 females and 20 males. Average age was 59.0 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses were 86.2%, 93.8%, and 60.9%, respectively. Patients experienced a mean reduction in proptosis of 3.2 ± 2.4 mm and mean improvement in CAS of 3.8 ± 1.6. Diplopia response was varied; patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (38.9% vs 69.6%, P =0.012) when compared with non-decompression patients. Acute patients also exhibited improved diplopia response (77.3% vs 51.2%, P = 0.022) after teprotumumab when compared to chronic patients. Otherwise, no other significant risk factors were found to be associated with proptosis, CAS, or diplopia responses. While most adverse events were mild to moderate, four patients reported serious adverse events related to persistent hearing loss.

Conclusions: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. Early treatment may result in improved diplopia outcomes, but further studies are needed to elucidate this relationship. These results indicate that TED recalcitrant to conventional therapies is responsive to teprotumumab and should be considered for the treatment of TED in patients who have failed prior therapies.