Real-world Data Highlight Benefits of Teprotumumab for Thyroid Eye, Graves Diseases

Study findings presented at the American Society of Ophthalmic Plastic & Reconstructive Surgery's 2021 Fall Scientific Symposium detail the benefits of teprotumumab for thyroid eye disease.

New research presented at the American Society of Ophthalmic Plastic & Reconstructive Surgery’s fall symposium highlighted the benefits of Tepezza (teprotumumab) for patients with thyroid eye and Graves disease.

Teprotumumab, a biologic, is the only FDA-approved treatment for thyroid eye disease. It is a targeted inhibitor of the insulin-like growth factor-1 receptor that is administered to patients once every 3 weeks for a total of 8 infusions.

In a multicenter retrospective study,1 researchers sought information on teprotumumab’s efficacy in patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose > 1 g), or prior biologic treatment, as these individuals were excluded from initial clinical trials.

Only individuals who received at least 4 infusions were included in the analysis (N = 52) while treatment failure was defined as “an incomplete response to previous treatment or recurrent active disease.”

Outcomes measured included clinical activity score (CAS), proptosis mean reduction and Gormon diplopia score (GDS), thyroid stimulating immunoglobulin, and Graves’ ophthalmopathy quality of life questionnaire (GO-QOL) scores.

The majority of patients assessed were female (n 42) and the average patient age was 56.3 years. In addition, mean patient follow-up time was 29.6 weeks.

Analyses revealed:

  • Mean reductions after 2 infusions: CAS of 2.8 (P < .001), proptosis of 2.6 mm (P < .001); GO-QOL increased an average of 38 points (P = .004)
  • Mean reductions after an average of 5 infusions: CAS of 3.6 (P < .001), proptosis of 4 mm (P < .001), and 61% of patients with baseline diplopia experienced a 1-point or better improvement in GDS
  • GO-QOL improved by 23 points (P = .029) overall

“The patients in this cohort demonstrated a significant improvement in each of the primary study outcomes,” the researchers concluded. “These results indicate that [thyroid eye disease] recalcitrant to conventional therapies is responsive to teprotumumab and should be considered for the treatment of recalcitrant [thyroid eye disease].”

A separate study2 presented at the meeting explored the effects of teprotumumab on volume of lacrimal glands and tear production. Dry eye syndrome is a common cause of discomfort among individuals with thyroid eye disease and can occur in up to 85% of patients, investigators explained, while eyelid manipulation plays an important role in disrupting the ability of the eyelids to protect the ocular surface.

“Recent work has shown that mechanical factors, such as upper eyelid retraction, interpalpebral fissure distance, or proptosis, were not predictive of the development of [dry eye syndrome] in patients with chronic [thyroid eye disease]. Enlargement of the lacrimal gland in [thyroid eye disease] has been found to correlate with subjective tearing,” they added.

The prospective longitudinal study enrolled individuals with thyroid eye disease and excluded those who were currently on treatment for the condition or received rituximab or tocilizumab in the past. In addition to change in volume of the lacrimal gland and production of tears after treatment with teprotumumab, the researchers also measured eyelid positions including margin-to-reflex distance (MRD), change in proptosis, and change in CAS.

Twenty individuals were enrolled in the study, with a mean age of 52 and mean (SD) duration of thyroid eye disease of 30 (35) months prior to therapy initiation. All patients completed 8 infusions of teprotumumab.

“Tear secretion was measured by the Schirmer test in each eye for 5 minutes. The orbit with the worse proptosis was designated as the study orbit,” authors wrote.

Analyses showed:

  • Clinically, the mean CAS for the study eye was 5 (1.7) at baseline and 0.7 (0.8) post treatment
  • Lacrimal gland volume decreased from 751 (349) to 418 (134) mm3 following treatment in the study orbit (P < .01)
  • In the fellow orbit, mean lacrimal gland volume decreased from 576 (301) to 417 (134) mm3 (P < .05)
  • Wetting in the study eye during Schirmer’s testing increased from 14.5 (10.5) mm at baseline to 22 (11) mm following treatment
  • There were no associations between MRD1, proptosis, steroid use, and duration of TED with lacrimal gland volume or tear production

Overall, the study revealed teprotumumab significantly reduced thyroid eye disease–related expansion of the lacrimal gland and increased tear production, while these changes were significant in patients with acute and chronic thyroid eye disease, the researchers concluded.

One additional study presented at the conference3 focused on reversal of Graves’ disease–associated facial volume expansion and eyelid changes in patients after they underwent teprotumumab treatment.

As thyroid eye disease can cause orbital soft tissue expansion and could result in brow and temple changes, researchers investigated changes to pan-facial soft tissue volumes and eyelid position among those who received teprotumumab.

Patients presenting to an institution for treatment for thyroid eye disease (n = 43) were included in the prospective study. However, those currently receiving treatment for the condition and “who had any plans to embark on a weight loss regimen or begin medications that may result in weight loss were excluded.”

Changes in tissue volume were assessed at baseline and 3 weeks after patients’ last infusion with teprotumumab. The mean duration of thyroid eye disease was 30 (34) months.

Measurements showed that following therapy, “mean decrease in volume for each region was 0.74 (0.82) mL in the upper face, 1.9 (1.2) mL in the periorbital region, 0.18 (0.6) mL in the temples, 1.73 (2.2) mL in the midface, and 2.84 (4.7) mL in the lower face.”

Furthermore, there was a mean decrease in volume of the full face 8.4 (8.5) mL and a significant reduction in MRD1, MRD2, and the intercanthal distance following treatment. “The contours of both upper and lower eyelids changed significantly following therapy (P < .05). Mean weight was 75 (12) kg prior to therapy and 69 (15) kg following therapy (P < .05),” the authors added.

No relationship was found between previous steroid use and reductions in total body weight or changes in facial volume among participants.

Despite the relatively small number of patients included in the study, the findings suggest thyroid eye disease sequalae “may affect soft tissues beyond the orbit and periorbita and may result in changes across the entire face,” while teprotumumab can significantly reduce these changes, in addition to eyelid retraction.


  1. Sears CM, Amarikwa L, Men C, et al. Teprotumumab for the treatment of recalcitrant thyroid eye disease. Presented at: ASOPRS Fall Scientific Symposium; November 11-12, 2021; New Orleans, LA. Accessed November 10, 2021.
  2. Ugradar S, Kim JS, Zimmerman E, Braun J, Mester T, Wang Y. Change in lacrimal gland volume and tear production following treatment with teprotumumab. Presented at: ASOPRS Fall Scientific Symposium; November 11-12, 2021; New Orleans, LA. Accessed November 10, 2021.
  3. Ugradar S, Kim JS, Victoria E, Braun J, Mester T, Wang Y. Reversal of Graves’ disease-associated facial volume expansion and eyelid changes following teprotumumab therapy. Presented at: ASOPRS Fall Scientific Symposium; November 11-12, 2021; New Orleans, LA. Accessed November 10, 2021.