Tepezza, or teprotumumab-trbw, is a prescription medication first approved by the U.S. Food and Drug Administration (FDA) in January 2020 for the treatment of Thyroid Eye Disease (TED), also known as Graves' ophthalmopathy. It was the first drug of its kind specifically for this condition, which is an autoimmune disorder where the immune system attacks the tissue behind the eyes, causing inflammation and symptoms such as bulging eyes, double vision, and pain. Tepezza is administered through a series of intravenous (IV) infusions over several months. While it has been shown to be effective, concerns about its safety profile have emerged since its approval, especially regarding hearing loss and other potentially serious side effects.
The Primary Concern: Hearing Impairment
One of the most significant and well-documented risks associated with Tepezza is hearing impairment, which can manifest as tinnitus (ringing in the ears) or, in some cases, severe and permanent hearing loss.
- Clinical Trial vs. Real-World Data: Initial clinical trials conducted by the manufacturer, Horizon Therapeutics (now part of Amgen), reported that approximately 10% of patients experienced hearing problems. However, subsequent real-world studies and post-marketing surveillance have suggested a much higher incidence. A 2021 study presented at the annual Endocrine Society meeting found that up to 65% of patients in their small sample reported hearing issues. By March 2025, over a quarter of all adverse event reports submitted to the FDA for Tepezza were ear-related.
- Potential Mechanism: The suspected mechanism for hearing loss involves Tepezza's role in inhibiting insulin-like growth factor-1 receptors (IGF-1R). IGF-1 is believed to play a protective role for the hair cells in the inner ear. By blocking IGF-1R, Tepezza may leave these delicate hair cells vulnerable to damage, leading to hearing loss.
- Label Change and Lawsuits: Due to mounting evidence of hearing-related risks, the FDA required the manufacturer to add a warning for severe and potentially permanent hearing loss to the drug's label in 2023. Furthermore, hundreds of lawsuits have been filed against Horizon Therapeutics, alleging the company failed to adequately warn patients and healthcare providers about the true extent of the risk, leading to legal action consolidated into multidistrict litigation (MDL).
Other Notable Side Effects and Risks
In addition to hearing issues, other serious and common side effects have been reported with Tepezza.
Serious Side Effects:
- Exacerbation of Inflammatory Bowel Disease (IBD): Patients with pre-existing IBD, such as Crohn's disease or ulcerative colitis, may experience a flare-up of their symptoms. In some cases, IBD exacerbation has been reported even in patients without a prior diagnosis.
- Hyperglycemia (High Blood Sugar): Tepezza can cause increased blood glucose levels. This is a particular concern for patients with pre-existing diabetes or impaired glucose tolerance and requires careful monitoring.
- Infusion Reactions: Approximately 4% of patients in clinical trials experienced infusion reactions, which can include temporary high blood pressure, rapid heartbeat, headache, or feeling hot. While usually mild to moderate, they may require adjusting the infusion rate or, in severe cases, discontinuing treatment.
- Embryo-Fetal Toxicity: Tepezza can cause harm to an unborn baby and is contraindicated during pregnancy. Women of childbearing potential must use effective contraception before, during, and for at least six months after the last dose.
Common Side Effects:
- Muscle cramps or spasms (25% in clinical trials)
- Nausea (17%)
- Hair loss or thinning (13%)
- Diarrhea (12%)
- Fatigue (12%)
- Changes in taste (8%)
- Dry skin (8%)
- Headache (8%)
Comparison of Hearing Impairment Risk Reporting
The reported incidence of hearing-related side effects has varied over time, highlighting the difference between controlled clinical trials and real-world data.
| Data Source | Reported Risk of Hearing Problems | Notes |
|---|---|---|
| Initial Clinical Trials | ~10% | Manufacturer's data used for FDA approval in 2020. Reportedly temporary in most cases. |
| Stanford 2021 Study | Up to 65% | Small observational study, found higher incidence and noted potential for permanence. |
| FDA Post-Marketing | >25% of adverse reports | Reports submitted to the FDA between 2020 and March 2025 showed a high proportion of ear-related events. |
| Recent Real-World Studies | ~46% | Other studies based on post-marketing data have cited higher percentages, suggesting early trial data underestimated the risk. |
Monitoring and Management
Given the serious risks, particularly hearing impairment, close monitoring is a critical component of Tepezza therapy. Healthcare providers should assess patients' health before, during, and after treatment.
- Hearing Monitoring: Baseline hearing assessments via audiometry are recommended before starting treatment, with follow-up testing during and after the full course of therapy. Patients should be advised to report any changes in hearing promptly.
- Glucose Monitoring: For patients with diabetes or hyperglycemia, blood glucose levels must be monitored carefully, and any necessary adjustments to diabetes medications should be made.
- IBD Monitoring: Patients with IBD require monitoring for disease flares. If an exacerbation is suspected, discontinuing Tepezza should be considered.
- Infusion Reaction Management: Healthcare professionals should be prepared to manage infusion reactions by slowing or stopping the infusion. Pre-medication with antihistamines, corticosteroids, or other medications may be used in subsequent infusions.
Conclusion: A Benefit-Risk Assessment
In conclusion, while Tepezza offers a valuable and effective treatment option for Thyroid Eye Disease, it is not without hazards. The most prominent risk is the potential for significant hearing impairment, which in some patients may be permanent. Other serious risks include the exacerbation of IBD, hyperglycemia, and potential harm to a fetus if taken during pregnancy. The fact that the manufacturer has faced legal action over allegations of inadequate warnings underscores the seriousness of these side effects. Patients considering or undergoing Tepezza treatment must have a thorough discussion with their healthcare provider to weigh the potential benefits of treating their TED against the notable risks and to establish a robust monitoring plan throughout the course of therapy.
For more detailed product and safety information, consult authoritative sources, such as the European Medicines Agency (EMA) Product Information.
