Thyroid eye disease (TED), also known as Graves’ orbitopathy, is a progressive autoimmune condition that can cause severe and lasting damage to eye health, function, and appearance. It affects the tissues around the eyes, leading to inflammation, swelling, and tissue remodeling that result in symptoms such as eye bulging (proptosis), double vision (diplopia), eye pain, and, in some cases, permanent vision loss.
TED treatment options were limited for decades, often relying on corticosteroids or surgery—until the recent approval of teprotumumab, a biologic therapy targeting the insulin-like growth factor-1 receptor (IGF-1R).
Teprotumumab, approved by the FDA in 2020, is the first medication specifically designed to treat TED at the molecular level. A pivotal publication by Dr. Raymond Douglas and colleagues in Ophthalmology has contributed significantly to our understanding of teprotumumab’s long-term efficacy and safety. This article explores how the drug is transforming the landscape of TED treatment for patients across all stages of the disease.
Understanding Teprotumumab’s Mechanism of Action
TED is caused by an autoimmune response in which antibodies mistakenly target the tissues around the eyes. This leads to orbital fibroblast activation, which produces excess hyaluronan and inflammatory mediators, causing tissue swelling and fibrosis. One of the key signaling pathways involved in this process is IGF-1R, which becomes overexpressed in TED-affected tissues.
Teprotumumab is a fully human monoclonal antibody that blocks IGF-1R, disrupting the cycle of inflammation and tissue expansion. Unlike steroids, which broadly suppress the immune system, teprotumumab explicitly targets the underlying biological mechanism of TED. This represents a major shift in how the disease is approached, addressing not just the symptoms but the root cause.
Clinical Trial Evidence
Teprotumumab’s approval and rapid adoption were driven by results from the OPTIC Phase 3 trial, a randomized, double-masked, placebo-controlled study involving patients with moderate-to-severe, active TED. The trial showed that 82.9% of patients receiving teprotumumab achieved a ≥2mm reduction in proptosis at 24 weeks, compared to just 9.5% in the placebo group. Improvements were also noted in the Clinical Activity Score (CAS), diplopia, and overall quality of life.
In the OPTIC-X extension trial, patients who had initially received a placebo or who relapsed after prior improvement were offered open-label teprotumumab. Many of these patients responded positively, including those with prolonged disease duration, highlighting the drug’s potential for long-term or recurrent TED.
Follow-up studies tracked outcomes up to 99 weeks post-treatment, showing that approximately 82% of patients maintained a durable response without further intervention. This evidence reinforces the drug’s long-term benefits and supports its use in a broader spectrum of TED cases, including those beyond the early inflammatory phase.
Teprotumumab vs. Traditional Therapies
Before teprotumumab, TED was primarily managed with high-dose corticosteroids, orbital radiation, or surgical intervention. Each approach carried limitations:
- Corticosteroids: While helpful in reducing inflammation, steroids are ineffective at reversing proptosis or fibrosis. Long-term use also comes with risks like weight gain, osteoporosis, hyperglycemia, and mood disturbances.
- Orbital radiation: Used to reduce inflammation, it offers a modest benefit and may not prevent disease progression. Risks include radiation retinopathy or optic neuropathy.
- Surgical interventions: These include orbital decompression, eyelid surgery, and strabismus repair. While often effective in restoring appearance and function, surgery is invasive, expensive, and typically reserved for the inactive phase of TED.
In contrast, teprotumumab is a non-surgical, disease-modifying therapy that can be used during the active phase and may prevent the need for surgery altogether. Its rapid onset and ability to reverse tissue changes make it a desirable option for many patients.
Safety Profile and Monitoring
Teprotumumab is generally well-tolerated, but like all biologics, it carries risks that require monitoring. Reported side effects include:
- Muscle spasms
- Nausea and gastrointestinal discomfort
- Hyperglycemia, especially in patients with diabetes or insulin resistance
- Hearing issues, such as tinnitus, hearing loss, or aural fullness
- Hair thinning or alopecia
While most side effects are mild to moderate, some patients may experience persistent hearing loss, prompting recommendations for baseline and follow-up hearing evaluations. Patients with diabetes should also undergo regular blood glucose monitoring during treatment.
Guidelines and Recommendations for Use
Leading ophthalmic organizations, including the American Academy of Ophthalmology (AAO) and EUGOGO, have updated their TED treatment guidelines to reflect the emergence of teprotumumab as a first-line therapy for moderate-to-severe, active TED.
According to expert consensus and clinical data:
- Teprotumumab is best suited for patients with recent-onset, active TED (typically within 9 months of symptom onset), particularly when proptosis or diplopia is progressing.
- Increasing evidence supports its use in patients with longer disease duration or chronic activity, as demonstrated in the OPTIC-X extension study.
- It is not typically recommended for mild TED, where supportive care or short-term steroid therapy may suffice.
Individualized patient assessment is essential, considering disease stage, comorbidities, and tolerance to previous treatments.
Insurance and Cost Considerations
One of the primary challenges surrounding teprotumumab is its high cost, with an entire treatment course often exceeding $300,000. However, the medication is now covered by many commercial insurance plans and Medicare Part B when prescribed for its FDA-approved indication.
Amgen, the manufacturer, offers the Amgen By Your Side™ program, which assists with benefits verification, prior authorization, and copay assistance. Many patients can access the medication with little to no out-of-pocket expense.
Looking Ahead: Expanding Use and Future Research
As the first drug for TED, teprotumumab has opened the door to further innovation. Current research is exploring:
- Retreatment protocols for patients who relapse
- Use in pediatric patients or those with milder forms of TED
- Biomarkers that predict treatment response
- Combination therapies with steroids or other immunomodulators
These studies aim to refine how, when, and for whom teprotumumab is most effective, advancing the move toward personalized medicine in TED care.
Final Thoughts
Teprotumumab represents a transformational advance in the treatment of thyroid eye disease. For the first time, patients have access to a non-surgical, disease-modifying therapy that addresses the root cause of TED rather than simply managing its symptoms.
While access and affordability remain concerns, teprotumumab has already changed the treatment landscape and offers new hope to thousands of patients living with the disfigurement, pain, and emotional toll of TED.
