Background/Purpose: Thyroid eye disease (TED) is a debilitating autoimmune disorder characterized by inflammation and exophthalmia along with significantly altered appearance and vision changes. TED is predominately associated with Graves’ disease, that can coexist with other autoimmune disease commonly managed by rheumatologists such as RA and SLE. Herein, we report results from the pooled 24-week randomized, double-masked, placebo-controlled, parallel-group, multicenter, Phase 2 (NCT01868997) and Phase 3 (NCT03298867) studies of teprotumumab, an insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, in adults with active, moderate-to-severe TED.

Methods: Patients (Pts) with recent onset of TED (< 9 months) were treated with a teprotumumab or placebo infusion every 3 weeks for a total of 8 infusions. Primary and secondary endpoint data were pooled between the two studies and included: the % of patients with a reduction in proptosis of ≥2 mm at week 24 in the study eye without similar fellow-eye worsening, overall responder rate (% of patients with ≥2 mm proptosis reduction AND ≥2-point clinical activity score [CAS] reduction in a 7-point scale) at week 24, CAS responder rate (% of patients with a CAS value of 0 or 1) at week 24, % of patients with an improved diplopia score at week 24, average proptosis and GO-QoL (TED specific quality of life questionnaire) score change from baseline through week 24, as compared with placebo.

Results: 171 pts were included in the intent-to-treat analyses (84 teprotumumab, 87 placebo). The demographics were as follows: mean age of 51.5 years (teprotumumab) vs 51.4 (placebo), 69% female (teprotumumab) vs 77% (placebo) and 76% non-smokers (teprotumumab) vs 70% (placebo). Significantly more teprotumumab pts had reductions in proptosis of ≥2 mm (65/84 [77.4%] vs 13/87 [14.9%], p< 0.001) and an overall response (% of pts meeting proptosis AND CAS outcome) (62/84 [73.8%] vs 12/87 [13.8%], p< 0.001) at week 24. The reduction in average change from baseline through week 24 in proptosis, was significantly greater in pts who received teprotumumab (-2.63 mm) than in those who received placebo (-0.31 mm, p< 0.001). The % of pts with absent TED activity (CAS of 0 or 1) was greater with teprotumumab at week 24 (52/84 [61.9%] vs 19/87 [21.8%], p< 0.001). The diplopia responder rate (% pts improved 1 or more grades) was significantly higher with teprotumumab (69.7%) vs placebo (30.5%; p< 0.001) in those with baseline diplopia (66 and 59 pts, respectively). Improvements in average change from baseline through week 24 in GO-QoL in overall score and subscales were significantly greater in the teprotumumab group (overall 15.55 vs 5.92, p< 0.001; visual functioning 16.81 vs 6.10, p< 0.001; appearance 13.51 vs 5.78, p=0.002).

Conclusion: In the largest placebo-controlled evaluation of active TED thus far conducted, teprotumumab reduced inflammation, proptosis, and diplopia resulting in clinical and quality of life improvements as compared with placebo over 24 weeks. Teprotumumab is a promising infused biologic option for TED, with implications for rheumatologists involved in managing patients with TED.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/teprotumumab-a-novel-biologic-for-active-thyroid-eye-disease/