Teprotumumab casts hope for thyroid eye disease

The human monoclonal anti-IGF-1R* antibody teprotumumab was effective in reducing proptosis or eye bulging in patients with the rare thyroid eye disease (TED) regardless of age, gender, and/or smoking status, according to pooled data presented at ENDO 2020.

The eye protrusion in TED patients may lead to a variety of symptoms (eg, eye pain, double vision, sensitivity to light, or difficulty closing affected eye) which, in turn, impair patients’ abilities to perform daily activities. [https://www.umkelloggeye.org/conditions-treatments/thyroid-eye-disease, accessed April 7, 2020]

“Teprotumumab decreases inflammation in the eye and the buildup of tissues behind the [symptomatic] eye, [thus improving the] quality of life [and offering] new hope for TED patients,” said lead researcher Dr George Kahaly from the Johannes Gutenberg University Medical Center in Mainz, Germany.

Researchers pooled data from two trials** comprising 171 patients with active TED associated with Graves’ disease. Participants were randomized 1:1 to receive teprotumumab or placebo. The study eye designated at baseline exhibited more severe TED and a clinical activity score of >4. Subjects were stratified by age at baseline, gender, and smoking status. [ENDO 2020, abstract OR18-01]

At week 24, there was a greater fraction of participants who responded well to teprotumumab than placebo, regardless of age (76 percent vs 16 percent [<65 years] and 85 percent vs 8 percent [≥65 years]), gender (73 percent vs 5 percent [male] and 79 percent vs 18 percent [female]), and smoking status (70 percent vs 23 percent [smokers] and 80 percent vs 12 percent [non-smokers]; p<0.001 for all).

These were confirmed in the continuous variable analysis as reflected by the significantly greater mean reductions in proptosis from baseline to week 24 with teprotumumab vs placebo, irrespective of age (-3.10 vs -0.39 mm [<65 years] and -3.55 vs -0.22 mm [≥65 years]), gender (-3.34 vs -0.07 mm [male] and -3.10 vs -0.42 mm [female]), and smoking status (-2.99 vs -0.72 mm [smokers] and -3.20 vs -0.31 mm [non-smokers]; p<0.001 for all).

Teprotumumab is the first drug that was recently approved by the FDA*** for TED. [https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-thyroid-eye-disease, accessed April 7, 2020] The current findings across different subgroups support the initial results showing significant reductions in eye bulging with teprotumumab vs placebo following 24 weeks of therapy. [N Engl J Med 2017;376:1748-1761; N Engl J Med 2020;382:341-352]