Introduction
Tepezza (teprotumumab-trbw) is a groundbreaking biologic medication developed by Horizon Therapeutics for the treatment of thyroid eye disease (TED), also known as Graves' ophthalmopathy. Approved by the FDA in January 2020, it represents the first and only medication specifically approved for this autoimmune condition that causes inflammation and tissue remodeling behind the eyes.
Mechanism of Action
Tepezza is a fully human monoclonal antibody that specifically targets and inhibits the insulin-like growth factor-1 receptor (IGF-1R). In thyroid eye disease, orbital fibroblasts express increased levels of IGF-1R. By blocking this receptor, Tepezza interrupts the inflammatory cascade and prevents the downstream signaling that leads to:
- Activation of orbital fibroblasts
- Production of hyaluronan and other glycosaminoglycans
- Tissue expansion and inflammation behind the eyes
- Adipogenesis in the orbital cavity
This mechanism ultimately reduces the characteristic signs and symptoms of TED, including proptosis (eye bulging), diplopia (double vision), and orbital inflammation.
Indications
Tepezza is indicated for the treatment of thyroid eye disease in adults. Clinical trials demonstrated effectiveness in patients with:
- Active thyroid eye disease (Clinical Activity Score ≥4)
- Duration of symptoms typically less than 9 months
- Moderate to severe disease characterized by proptosis, diplopia, and inflammatory signs
Dosage and Administration
Initial dose: 10 mg/kg administered as an intravenous infusion over 90 minutes Subsequent doses: 20 mg/kg administered as an intravenous infusion over 90 minutes every 3 weeks for a total of 8 infusions Administration considerations:- Premedication with an antihistamine and corticosteroid is recommended to minimize infusion reactions
- Infusion rate may be extended if tolerated
- Dose adjustments are not required for renal or hepatic impairment
- No dosage adjustment recommended for elderly patients
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Steady-state volume of distribution is approximately 7.9 L Metabolism: Expected to undergo catabolic pathways typical of immunoglobulin G1 antibodies Elimination: Terminal half-life is approximately 20 days Clearance: Linear clearance at the recommended dosage regimenContraindications
Tepezza is contraindicated in patients with:
- Known hypersensitivity to teprotumumab or any component of the formulation
- Uncontrolled hyperglycemia (due to risk of exacerbation)
Warnings and Precautions
Hyperglycemia: May cause hyperglycemia. Patients with preexisting diabetes should have blood glucose monitored closely. Hearing impairment: May cause hearing impairment, including hearing loss, tinnitus, and feeling of fullness in the ear. Infusion reactions: May occur during or following infusion. Premedication and monitoring during infusion are recommended. Inflammatory bowel disease: Exacerbation of preexisting inflammatory bowel disease may occur. Pregnancy: May cause fetal harm based on animal data. Effective contraception should be used during treatment and for 6 months after final dose.Drug Interactions
Formal drug interaction studies have not been conducted. However, considerations include:
- Other diabetogenic medications: May have additive effects on blood glucose
- Immunosuppressants: Potential for increased risk of infections
- Live vaccines: Not recommended during treatment due to potential reduced vaccine efficacy
Adverse Effects
Most common adverse reactions (≥10%):- Muscle spasm (25%)
- Nausea (17%)
- Alopecia (13%)
- Hyperglycemia (12%)
- Fatigue (12%)
- Hearing impairment (10%)
- Diarrhea (10%)
- Headache (10%)
- Exacerbation of preexisting inflammatory bowel disease
- Severe hyperglycemia requiring hospitalization
- Significant hearing impairment
- Severe infusion reactions
Monitoring Parameters
Baseline assessment:- Complete ophthalmologic evaluation
- Hearing assessment
- Blood glucose/HbA1c
- Pregnancy test in women of childbearing potential
- Assessment of inflammatory bowel disease history
- Blood glucose monitoring before each infusion
- Regular assessment of hearing function
- Monitoring for infusion reactions during each administration
- Ophthalmologic assessments at regular intervals
- Assessment of inflammatory bowel disease symptoms
- Continued monitoring for hearing changes
- Blood glucose monitoring for several months
- Ophthalmologic follow-up
Patient Education
Key points to discuss with patients:- Tepezza is administered as intravenous infusions every 3 weeks for 8 total treatments
- Report any signs of infusion reactions during or after treatment
- Monitor blood glucose regularly if you have diabetes
- Report any changes in hearing, ringing in ears, or ear fullness
- Inform healthcare providers about any history of inflammatory bowel disease
- Use effective contraception during treatment and for 6 months after final dose
- Do not receive live vaccines while taking Tepezza
- Most common side effects include muscle spasms, nausea, hair loss, and fatigue
- Keep all scheduled appointments for infusions and monitoring
References
1. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017;376(18):1748-1761. 2. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020;382(4):341-352. 3. Tepezza [package insert]. Horizon Therapeutics USA, Inc.; 2020. 4. Ugradar S, Kang J, Kossler AL, et al. Teprotumumab for the treatment of chronic thyroid eye disease. Eye (Lond). 2022;36(8):1553-1559. 5. FDA Approval Letter: Tepezza. January 21, 2020. 6. Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021;185(4):G43-G67.