Thyroid Eye Disease and the Need for Alternative Therapies: Enter Tepezza

Patients with Thyroid Eye Disease no longer need to wait. The FDA has recently approved the drug Tepezza (teprotumumab-trbw) for the treatment of thyroid eye disease. Tepezza boasts a breakthrough mechanism of action that brings light to the complexity of thyroid eye disease.

Background

Thyroid eye disease (TED), also called Graves’ Eye Disease or Graves’ Ophthalmopathy, is a complication of the eye that originates in patients with Graves’ disease. Graves’ disease is an autoimmune disorder where your body consistently attacks the thyroid, resulting in an overproduction of thyroid hormone. The most common complication of Graves’ disease is hyperthyroidism. The resulting hyperthyroidism, which over-expresses the thyroid-stimulating hormone (TSH), activates thyroid-stimulating hormone receptor (TSHR). TSHR is closely aligned to the insulin-like glucose factor 1 (IGF-1) receptor. In the end, the activated TSHR and IGF-1 receptors create a retro-orbital inflammation environment.

The diagnosis of TED tends to be obvious. With the inflammation that arises, comes proptosis (bulging of the eyes) and periorbital edema (puffy eyes). While physical observations may bring about an obvious diagnosis, measurements of serum TSHR can help confirm TED as well as the severity of the condition.

Treatment Approach

Before the option of Tepezza existed, the treatment approach for TED focused on the reversal of the hyperthyroidism. The reversal of the hyperthyroidism should decrease the possibility of unwanted inflammation. Mild cases of thyroid eye disease are more often treated with local measures, such as artificial tears. These local measures often lead to relief of the eye when the corneal responds to the lubricants and the proptosis present is <3 mm.

Moderate-to-severe symptoms of TED need increased anti-inflammation treatment properties due to the markedly increased inflammation. Moderate symptoms tend to include inflamed eyes and increasing diplopia or proptosis >3 mm. Initially, glucocorticoids are suggested to combat this inflammation. While glucocorticoids may be effective in most, contraindications and intolerance to glucocorticoids is all too common. When glucocorticoids are no longer feasible, alternative medical therapies are needed and in steps Tepezza.

Mechanism

While many would think that Tepezza would function around the thyroid itself or the thyroid hormones involved, it instead works with the insulin-like growth factor-1 receptor. The IGF-1, discussed earlier, is closely aligned to TSHR. Tepezza binds to the insulin-like growth factor-1 receptor inhibitor and blocks its activation and signaling. The active ingredient of Tepezza, teprotumumab, is a humanized monoclonal antibody.

Trials

The trials that accompanied Tepezza, and paved its way to the FDA approval, showed great efficacy compared to placebo. Two randomized trials showed the proptosis size drastically decrease compared to placebo. One study showed a decrease of 2.5 mm while the other study had a 2.8 mm decrease. The response rate, which was considered as any patient with a >2 mm reduction, was drastic and occurred in 71% of patients in one trial and 83% in the other. With moderate-to-severe cases of TED diagnosed at proptosis size >3 mm, reducing that by roughly 2 mm is an exceptional response.

Conclusion

The treatment approaches for TED are few, accompanying a lean toward an inability to control the disease state. The idea of a new medication hitting the market to help fill that void would we welcoming, even if it showed just relative promise. The fact that Tepezza, accompanied by its novel mechanism, gained its FDA approval and showed strikingly positive results shows just how important this medication can be. It may fill the void needed in treating severe thyroid eye disease while also setting a benchmark for effectiveness. While more trials will need to be done, emphasized on different populations and increased population size, Tepezza is an astonishing step forward in the right direction.

Thank you For Reading,

Aaron Forsythe LECOM School of Pharmacy

References

Davies, TF. Treatment of Graves’ orbitopathy (ophthalmopathy). In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2020.

“Graves’ Eye Disease.” American Thyroid Association, www.thyroid.org/graves-eye-disease/.

Horizon Therapeutics. (2020). Tepezza: Full Prescribing Information. Lake Forest, IL: Author.

Lexicomp. Teprotumumab: Drug information. In: UpToDate, Post T, (ed), UpToDate, Waltham, MA: Accessed April 15, 2020.

“The First and Only FDA-Approved Treatment for Thyroid Eye Disease (TED) Is Here.” TEPEZZA (Teprotumumab-Trbw) Thyroid Eye Disease Treatment | HCP Home, www.tepezza.com/hcp/.