Is a Second or Third Course of Tepezza Common for Thyroid Eye Disease?

Thyroid Eye Disease (TED) is a complex, autoimmune disease that can cause inflammation and remodeling of the tissues around the eyes with symptoms such as eye bulging (proptosis), pain and irritation, double vision (diplopia), and visual fatigue (1-3). Tepezza (Tepezza®/teprotumumab-trbw) has transformed the treatment of TED, offering many patients meaningful improvements in associated symptoms and quality of life without the need for immediate surgery. Since its FDA approval in 2020, the standard treatment regimen for Tepezza has been eight intravenous infusions over approximately five months (4).

Most patients who complete the standard course of Tepezza do not require additional treatment. However, because TED is an autoimmune disease that can reactivate and does not respond completely to treatment, a small percentage of patients may benefit from retreatment. Understanding when retreatment is considered and why it remains relatively uncommon can help this subset of patients to maintain realistic expectations.

The Standard Course of Tepezza for Thyroid Eye Disease

Tepezza is administered as a series of eight intravenous infusions, given every three weeks. Unlike treatments that simply suppress inflammation, Tepezza targets the insulin-like growth factor-1 receptor (IGF-1R), a key driver of the autoimmune process underlying TED. Clinical trials demonstrated significant improvements in symptoms such as eye bulging (proptosis), double vision (diplopia), soft tissue inflammation, Clinical Activity Scores (CAS) and overall quality of life. Many patients also experienced durable improvements, allowing them to avoid or delay reconstructive surgery.

How Common Is a Second Course of Tepezza?

Real-world evidence suggests that the vast majority of patients do not require another full course of Tepezza (5). In one large real-world analysis of 5,845 patients who completed the full eight-infusion regimen, only 4.9% of patients received a second course of Tepezza during approximately two years of follow-up. Among those who required retreatment, the average time between both courses was approximately 12 months. Although uncommon, retreatment may be considered in select patients, including those with:

Disease Reactivation: Because TED is an autoimmune disorder, it may fluctuate between active and inactive phases. Research has shown that approximately 15% of patients with TED may experience a disease flare, regardless of their initial treatment. Potential triggers include physiological stress, pregnancy, changes in immune activity, surgery and other less understood factors that have been associated with relapse flares. A flare may involve one or a combination of renewed inflammation, increased eye bulging, worsening double vision, or pain behind the eyes.

Incomplete Initial Response: Unfortunately, response to TEPZZA varies, and not every patient experiences the same level of improvement. Some individuals may improve substantially in one area or symptoms, for example, inflammation, but continue to have bothersome proptosis or diplopia. So, an additional course of Tepezza depends on numerous factors, including, current disease activity, duration of symptoms, imaging findings and overall treatment goals. In certain cases, additional surgery rather than repeat medication becomes the better solution.

Individual Variation: No two patients with TED are alike, with disease severity, duration, smoking history, thyroid control, genetics, and immune activity all influencing how patients respond to treatment. This variability explains why treatment decisions must always be individualized.

Does a Second Course Mean the First One Failed?

Not necessarily, as TED progression does not follow a ‘one size fits all’ pattern in different patients. Some individuals experience prolonged remission after treatment and others develop recurrent immune activation months or years later. An additional treatment is indicative of the behavior of the underlying autoimmune underpinnings and not necessarily a failure of the medication. This distinction is important because patients often assume recurrence means the original treatment stopped working, while, in reality, the autoimmune component may have flared up again.

What Current Evidence Shows Regarding a Third Course of Tepezza

The available evidence suggests that three courses of Tepezza are uncommon. Most published data primarily focus on two treatment courses because relatively few patients have required additional therapy beyond that point. If symptoms relapse even after a second course, physicians often reassess the underlying cause before recommending another round of medication. This is because persistent symptoms may reflect structural changes rather than active inflammation, fibrosis (scar tissue), residual proptosis and chronic double vision. These structural issues often respond better to reconstructive surgery than to additional biologic therapy.

How Doctors Decide on Tepezza Retreatment

An immediate recourse to a second Tepezza infusion upon relapse is rarely the case and specialists always perform a comprehensive evaluation before deciding. This generally includes a thorough review of symptom progression, Clinical Activity Scores (CAS) assessment, eye movement examination, vision testing, measurement of proptosis and orbital imaging where appropriate. The deciding question is one of active inflammation versus symptoms from permanent structural changes. If inflammation has subsided but residual eye bulging remains, surgery may offer greater benefit than another course of medication.

When Surgery May Be Preferred Over Another Course

While Tepezza is designed to reduce active inflammation and tissue expansion, once chronic structural changes develop, surgery often becomes the preferred treatment. Surgical options may include orbital decompression for persistent proptosis, strabismus surgery for chronic double vision, and/or eyelid surgery for eyelid retraction. Recent studies have shown that while Tepezza has reduced the overall number of orbital decompression procedures, surgery still remains necessary for selected patients whose anatomy or symptoms do not fully normalize after medical therapy. Rather than viewing medication and surgery as competing options, they should be considered complementary treatments that address different phases of TED.

These differing approaches converge upon an important point; retreatment is influenced by patient selection, disease severity, physician practice patterns, disease relapses and follow-up duration. Larger, long-term studies will continue to clarify which patients are most likely to benefit from another course.

Reducing the Risk of Relapse or Retreatment

While no strategy guarantees permanent remission, maintaining stable thyroid hormone levels can support better long-term outcomes. It is important to understand that thyroid control does not eliminate TED, but keeping thyroid levels within a healthy range can help prevent the negative impact that uncontrolled thyroid levels may have on TED symptoms and disease progression.

Some strategies include avoiding cigarette smoking and attending regular follow-up appointments. Reporting new symptoms promptly and working closely with both their endocrinologist and TED specialist. Early recognition of recurrent inflammation allows physicians to intervene before permanent structural changes develop.

When to Seek Medical Advice About Tepezza Treatment Plans

Most patients show remarkable improvement with a single course of Tepezza and the need for additional treatment remains relatively uncommon. Real-world data indicate that fewer than 5% of patients are prescribed a second course within two years. When a second course is recommended, it is typically because of TED reactivation due to inflammation or because significant active inflammatory disease remains after the initial treatment.

The most important caveat is that this decision is taken based on the nature of the underlying reasons governing symptom relapse rather than relapse alone. Working with an experienced TED specialist ensures that each stage and type of treatment is tailored to your specific condition and aimed at helping achieve the best possible outcome while avoiding unnecessary interventions.

If you have completed a course of Tepezza and are experiencing a relapse in symptoms or are simply interested in learning more about Tepezza repeat dosing, schedule an appointment with Dr. Raymond Douglas without delay.

References

1. Shah SS, Patel BC. Thyroid Eye Disease.  StatPearls. Treasure Island (FL)2025.
2. Wiersinga WM, Eckstein AK, Zarkovic M. Thyroid eye disease (Graves’ orbitopathy): clinical presentation, epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol. 2025;13(7):600-14. Epub 20250502. doi: 10.1016/S2213-8587(25)00066-X. PubMed PMID: 40324443.
3. <autoimmune_diseases_and_your_environment_508.pdf>.
4. Couch SM. Teprotumumab (Tepezza) for Thyroid Eye Disease. Mo Med. 2022;119(1):36-41. PubMed PMID: 36033157; PMCID: PMC9312457.
5. Douglas RS, Kahaly GJ, Ugradar S, Elflein H, Ponto KA, Fowler BT, Dailey R, Harris GJ, Schiffman J, Tang R, Wester S, Jain AP, Marcocci C, Marino M, Antonelli A, Eckstein A, Fuhrer-Sakel D, Salvi M, Sile S, Francis-Sedlak M, Holt RJ, Smith TJ. Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study. Ophthalmology. 2022;129(4):438-49. Epub 20211021. doi: 10.1016/j.ophtha.2021.10.017. PubMed PMID: 34688699.