Tepezza treatment correlates to improved extraocular muscle size, clinical outcomes
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CHICAGO — Patients who received Tepezza to treat thyroid eye disease showed improved extraocular muscle size that correlated to improved diplopia and motility, according to a presenter here.
“Thyroid eye disease is known to cause inflammation, expansion and fibrosis of extraocular muscles and connective tissue of the orbit. The mechanism involves upregulation of TSHR and IGF-1R complex in orbital fibroblasts,” Edith R. Reshef, MD, of Massachusetts Eye and Ear, said at the ASOPRS Fall Scientific Symposium. “Teprotumumab inhibits this pathway, thereby decreasing inflammatory response. The purpose of this study was to assess and quantify changes in extraocular muscle size as measured by cross-sectional area on CT in TED following teprotumumab therapy. We also sought to assess correlation between changes in extraocular muscle size and clinical outcomes of teprotumumab therapy.”
In the retrospective longitudinal study, Reshef and colleagues looked at all patients with thyroid eye disease (TED) from February 2020 to March 2022 using pre- and post-treatment CT to determine the impact of Tepezza (teprotumumab, Horizon Therapeutics) therapy on extraocular muscle size. They excluded patients with prior orbital decompression or strabismus surgery, those whose pre-treatment CT was more than 2 years before treatment and those who had an incomplete treatment course.
Primary outcomes were the change in total extraocular muscle to orbit cross-sectional area ratio and the change in each individual muscle to orbit cross-sectional area ratio. Secondary outcomes included stratification based on age, clinical activity scores (CAS) and correlation of area ratio to change in outcome measures.
Reshef presented data on 48 eyes of 24 patients. She said 41.7% had prior treatment for TED and 87.5% had a CAS of 4 or greater.
The overall results showed improvements in the medial rectus (–17.24%; P < .001), the inferior rectus (–15.25%; P = .0006), the superior rectus (–26.67%; P < .001), the lateral rectus (–19.27%; P < .001), the superior oblique (–5.18%) and a total reduction in extraocular muscle (–18.17%; P < .001).
“There was a significant improvement in the total extraocular muscle ratio with an 18% reduction. Likewise, for each individual muscle, there is a reduction,” Reshef said.
When stratified by age, Reshef showed that the 19 patients aged 40 years and older improved from 0.52 ± 0.06 mm2 to 0.44 ± 0.23 mm2 (P < .001) and those younger than 40 years improved from 0.33 ± 0.04 mm2 to 0.25 ± 0.07 mm2 (P < .001).
“There was a significant improvement in area ratios for the age greater than 40 group as well as the age less than 40 group,” Reshef said. “This raises the idea that perhaps for the type 1 younger patients with smaller muscles, they still do show a significant improvement reduction in size.”
When stratified by CAS, those with a CAS of 4 or greater improved from 5.1 ± 0.96 mm2 to 0.6 ± 0.81 mm2 (P < .001) while those with a CAS less than 4 improved from 2 ± 1.07 mm2 to 0.75 ± 0.89 mm2.
Looking at individual clinical outcomes, CAS improved by 3.95 ± 1.58 (P < .001), proptosis decreased by 3.47 ± 2.26 mm (P < .001), diplopia improved by 0.57 ± 0.83 (P = .01), and extraocular motility improved by –1.67 ± 1.6 (P < .001).
“There was a significant correlation between the reduction of cross-sectional area ratios and the reduction of the diplopia score as well as the extraocular motility,” Reshef said, although that correlation did not extend to the other two clinical outcomes.
“Our study shows that extraocular muscle size is significantly reduced following teprotumumab, and this suggests anatomic correlate to the molecular mechanism of the drug,” she said. “The radiographic changes that we see correlate to clinical responses that we see following treatment, and more notably, the reduction of extraocular muscle size is significantly correlated to improvement in diplopia and extraocular motility.”
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Reshef ER, et al. Reduction in extraocular muscle cross-sectional area following teprotumumab for thyroid eye disease. Presented at: ASOPRS Fall Scientific Symposium; Sept. 29-30, 2022; Chicago.
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