Teprotumumab Improves Thyroid Eye Disease Across Phenotypes

NEW ORLEANS — Comparable improvements were observed with teprotumumab (Tepezza) between patients with age-related phenotypic I or II thyroid eye disease, according to results from a post-hoc analysis.

At 24 weeks, 81% of patients with phenotypic I thyroid eye disease (those younger than 40 years) and 73.7% of those with phenotypic II disease (those 40 and older) had overall improvements with teprotumumab, a difference that was not statistically significant (P=0.535), reported Soheab Ugradar, MD, of Thrive Health in Beverly Hills, California, during an oral presentation at the American Association of Clinical Endocrinology annual meeting.

Results with teprotumumab was also similar between the younger and older patients for proptosis, diplopia, clinical activity score, and Graves’ Ophthalmology Quality of Life score.

Session moderator Capt. Thanh Hoang, DO, director of the fellowship program in endocrinology at Walter Reed National Military Medical Center in Bethesda, Maryland, noted that “I like this drug a lot for my patients with thyroid eye disease because before this drug was available, patients required a lot of surgery or the use of steroids, which have a lot of side effects. Patients respond very well to this drug, although some may recur after a few months.”

Hoang said he would not treat patients based on the age cutoff used in the analysis. “That is sort of arbitrary. We would do more testing to determine the phenotype, but [we would also take] a family history and consider the clinical activity score to find out the severity of the disease and to see if there was an appropriate medication.”

“Overall, however, this drug seems to work among all patients, no matter what the phenotype. That is what I am seeing in my practice, as well,” he added.

For this analysis, Ugradar and colleagues identified patients in the randomized OPTIC trial and the open-label OPTIC-X trial, in which patients received 8 infusions of teprotumumab.

They included 121 patients, 22 with phenotypic 1 disease and 99 with phenotypic 2 disease. For the patients with type I disease, mean age was 32.8, 59.1% were women, 81.8% were white, mean time since diagnosis was 8.6 months, and mean clinical activity score was 4.1. For the patients with type II disease, mean age was 54.5, 72.7% were women, 86.9% were white, mean time since diagnosis was 7.7 months, and mean clinical activity score was 4.8.

Phenotypic I thyroid eye disease involves orbital fat expansion and proptosis with minimal to no periorbital inflammation or diplopia, with low rates of dysthyroid optic neuropathy, while phenotypic II thyroid eye disease involves extraocular muscle enlargement and fibrosis, diplopia, and periorbital inflammation, with higher rates of dysthyroid optic neuropathy.

At 24 weeks, the least squares mean change in proptosis was -3.46 mm for the younger patients and -3.22 mm for the older patients (P=0.525). Ugradar said that a change of 3 mm, considered the usual correction achieved with surgery, was clinically meaningful.

For the quality-of-life score, the total least squares mean change at week 24 was 19.09 points in the younger patients and 15.96 points in the older patients (P=0.446).

Looking at 42 patients with longer-duration thyroid eye disease and clinical activity scores of ≤1 (mean age 32 for the younger patients and 56.1 for the older patients), responses at week 24 were similar between the younger and older patients for proptosis (61.5% vs 62.1%, respectively) and diplopia (50% vs 40%).

The least squares mean change in proptosis was -2.0 mm for the younger patients and -2.6 mm for the older patients (P=0.275), and the least squares mean change in quality-of-life score appearance subscale was 12.95 points and 8.32 points, respectively (P=0.625), and 5 points and 8.68 points for the visual function subscale (P=0.158).