Thyroid Eye Disease

Teprotumumab: A Potential Game-Changer for Thyroid Eye Disease

Sonal Tuli, MD
Professor and Chair, Department of Ophthalmology University of Florida College of Medicine

Chief of Ophthalmology, University of Florida Health, Gainesville, Florida

Tuli S. Teprotumumab: a potential game-changer for thyroid eye disease [Published online February 18, 2020]. Consultant360.


Thyroid eye disease (TED) or thyroid-associated ophthalmopathy (TAO) is a poorly understood disease typically associated with hyperthyroidism or Graves’ disease.1 It is thought to be secondary to the autoimmune process rather than the excess thyroid hormone itself.1

Insulin-like growth factor I receptor (IGF-IR) is implicated as a potential cause of TAO, and overexpression of IGF-IR is found in orbital fibroblasts and lymphocytes.2 Features of TAO include periorbital edema, proptosis, strabismus, and eyelid retraction, which can progress to vision-threatening complications, such as exposure keratopathy and compression neuropathy.1 Current management of this condition is not very effective and includes systemic steroids or radiation of the orbit, both of which are associated with significant adverse effects and complications.1

In January 2020, the US Food and Drug Administration approved teprotumumab (Tepezza), a human IGF-IR–inhibitory monoclonal antibody, for the treatment of TED.3 This approval was based on a randomized, multicenter, placebo-controlled clinical trial of 88 participants with active moderate to severe ophthalmopathy.4 A total of 8 infusions of the medication or placebo were given intravenously every 3 weeks, and outcomes measured at 24 weeks were a reduction in proptosis by 2 mm or more and an improvement in the Clinical Activity Score (CAS) by 2 points or more.4 The researchers found that significantly more participants had met these endpoints with teprotumumab compared with placebo, and that the effects were rapid and seen as early as 6 weeks.4

Subsequently, the OPTIC trial (N = 83), a phase 3 clinical trial, repeated the intervention at 13 sites in the United States and Europe.5 This trial focused on meaningful reductions in proptosis as the primary outcome.5 The results were similar to the first trial, with significantly more participants in the teprotumumab group experiencing an improvement in proptosis, diplopia, CAS, and quality of life compared with the placebo group.5 Imaging was also performed on a small number of participants and revealed that a reduction in proptosis was associated with reductions in extraocular muscle volume and/or orbital fat volume.5 Some of the responses shown in the trial were very dramatic.5 Participants who did not have a response in terms of proptosis reduction, or had a response followed by a relapse, could enter an ongoing, open-label extension of the study (OPTIC-X), during which participants will receive 8 additional infusions of teprotumumab.6

Adverse effects were seen in approximately three-quarters of the participants in both studies, but the majority were mild and did not require discontinuation of the medication.4,5 Severe adverse effects were relatively rare. Six participants discontinued the medication in each group in the first trial, and 2 discontinued in each group in the second trial due to adverse effects.4,5 The only adverse effect definitively identified as associated with teprotumumab use was hyperglycemia in participants with diabetes, but it did not require discontinuation of teprotumumab and could be controlled with adjustment of diabetes medication.4

In summary, teprotumumab is an exciting, first-in-kind medication that has shown impressive efficacy in reducing proptosis, as well as other complications of TED. The amount of reduction in proptosis is similar to that with orbital decompression surgery, which is associated with significant complications including exacerbation of the inflammation and worsening of the strabismus. This medication has the potential of being a game-changer in the treatment of TED.


  1. Şahlı E, Gündüz K. Thyroid-associated ophthalmopathy. Turk J Ophthalmol. 2017;47(2): 94-105. doi:10.4274/tjo.80688.
  2. Smith TJ. The insulin-like growth factor-I receptor and its role in thyroid-associated ophthalmopathy. Eye. 2019;33:200-205.
  3. FDA approves first treatment for thyroid eye disease [press release]. US Food and Drug Administration. January 21, 2020. Accessed February 10, 2020.
  4. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748-1761. doi:10.1056/NEJMoa1614949.
  5. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382:341-352. doi:10.1056/NEJMoa1910434.
  6. Horizon Pharma USA, Inc. Treatment of Graves' orbitopathy to reduce proptosis with teprotumumab infusions in an open-label clinical extension study (OPTIC-X). NCT03461211. Accessed February 10, 2020.