Teprotumumab (Tepezza), Game Changer in Thyroid Eye Disease

Teri Kleinberg, MD, MSc

Thyroid eye disease, or ted, is a beast with many names including Graves’ ophthalmopathy, thyroid-related orbitopathy and dysthyroid orbitopathy. Regardless of what you choose to call this constellation of clinical findings, it is a disfiguring, debilitating and progressive disease that affects both psychological and functional well-being. TED affects 1.9 cases per 10,000 population per year (1) and can range from mild dry eye symptoms to massive proptosis, double vision and vision loss from compressive optic neuropathy. Many of us see these patients and work closely in multidisciplinary teams that may include internal or family medicine, endocrinology, ophthalmology, radiation oncology and otorhinolaryngology.

Prior to 2020, there was no medical therapy approved by the U.S. Food and Drug Administration for TED. As an oculoplastic specialist, I have had limited tools in my arsenal. Initial treatment usually consists of aggressive lubrication and treatments for the ocular surface. Clinical signs of inflammation would bring on the steroids, either oral or intravenous, along with myriad familiar side effects without meaningful improvements in reduction of proptosis or alteration of the natural progression of the disease. (2) Occasionally, I will send patients to my radiation oncology colleagues for orbital radiation to reduce inflammation. Once the clinical exam stabilizes, over sometimes two to three years, I can consider surgery for my patients. These procedures include orbital decompression to reduce proptosis, strabismus surgery to help with diplopia, and eyelid surgery for lid retraction and to improve cosmesis and eyelid closure. Infrequently, terrible compressive optic neuropathy will necessitate emergent orbital decompression along with pulse doses of steroids in the hopes of preventing irreversible vision loss.

The real game changer in this disease was FDA approval of teprotumumab in 2020. Teprotumumab, or Tepezza, is a monoclonal antibody against insulin-lik growth factor I receptor, IGF-1R, which has been implicated in the pathogenesis of this disease. (2) It is the only treatment shown to reduce double vision and proptosis in TED patients. In the phase-three multicenter OPTIC trial, 83% of treatment arm patients had reduction of proptosis of at least 2 millimeters versus 10% in the control group. A majority, 68%, of patients had reduction in diplopia versus 29% in the control group. (3) Teprotumumab has been shown to have clinically significant as well as durable treatment effects for at least one year with longer observational studies coming down the pipeline. (3) Use of this agenct involves an eight-infusion series performed every three weeks over a total treatment period of 24 weeks. Known contraindications are poorly controlled diabetes, irritable bowel syndrome, and pregnancy. Significant side effects that occurred in over 5% of patients in the aggregate of both published studies include muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (12%), fatigue (12%), hyperglycemia (10%), hearing impairment (10%), dysgeusia (8%), headaches (8%) and dry skin (8%). (3,4) It is worth noting that 89% of the treatment group completed the full course of treatment. (3,4)

Unfortunately, as with most novel treatments, the most challenging part of this treatment is obtaining prior authorization and coverage from insurance companies. The estimated cost of the full series of infusions is approximately $200,000 (5). Insurance coverage of this medication will — at least in the near future — be the primary limiting factor for obtaining this game-changing treatment. + Teri Kleinberg, MD, MSc is an ophthalmologist and oculoplastic specialist in private practice at Worcester Ophthalmology Associates. She is a proud graduate of The University of Massachusetts Chan Medical School Class of 2010. She participates in medical student teaching through the Leadership & Professionalism fourth-year elective course in the Department of Family Medicine. She is also on the executive board of the Massachusetts Society of Eye Physicians and Surgeons. She can be reached at 508-421-2010 or via email at tkleinbergmd@ woadocs.com.

Tepezza trial patient baseline photo demonstrating 24 mm of proptosis, eyelid swelling, conjunctival injection chemoses, and inflammation of the caruncle. Image reproduced with permission from Horizon Pharmaceuticals.

Tepezza trial patient baseline photo demonstrating 24 mm of proptosis, eyelid swelling, conjunctival injection chemoses, and inflammation of the caruncle. Image reproduced with permission from Horizon Pharmaceuticals.

Tepezza trial patient post-treatment (week 24) photo demonstrating reduction of proptosis to 19 mm and mild residual eyelid swelling. Image reproduced with permission from Horizon Pharmaceuticals.

References:

1. Smith, T. J., & Hegedüs, L. (2016). Graves’ disease. New England Journal of Medicine, 375(16), 1552- 1565.

2. Slentz, D. H., Smith, T. J., Kim, D. S., & Joseph, S. S. (2021). Teprotumumab for optic neuropathy in thyroid eye disease. JAMA ophthalmology, 139(2), 244-247.

3. Douglas, R. S., Kahaly, G. J., Patel, A., Sile, S., Thompson, E. H., Perdok, R., ... & Smith, T. J. (2020). Teprotumumab for the treatment of active thyroid eye disease. New England Journal of Medicine, 382(4), 341-352.

4. Smith, T. J., Kahaly, G. J., Ezra, D. G., Fleming, J. C., Dailey, R. A., Tang, R. A., ... & Douglas, R. S. (2017). Teprotumumab for thyroid-associated ophthalmopathy. New England Journal of Medicine, 376(18), 1748- 1761.

5. https://www.aao.org/eye-health/ news/tepezza-nonsurgical-treatment-thyroid-eye-disease