Is repeating Tepezza (Teprotumumab) treatment medically indicated for a patient with worsening thyroid eye disease (TED), including diplopia and exophthalmos, who has previously received a full round of 8 infusions?

Repeating Tepezza Treatment is Medically Indicated for This Patient

Yes, repeating Tepezza (teprotumumab) treatment is medically indicated for this 59-year-old male with worsening thyroid eye disease, including diplopia and exophthalmos, who previously completed 8 infusions. The FDA has approved Tepezza for the treatment of thyroid eye disease regardless of disease activity or duration, and the evidence strongly supports retreatment in patients experiencing disease flare or recurrence 1.

FDA Approval and Guideline Support

• The FDA indication explicitly states that Tepezza is approved for treatment of TED "regardless of Thyroid Eye Disease activity or duration," which directly supports retreatment in this clinical scenario 1.
• The American Academy of Ophthalmology guidelines recognize that teprotumumab reduces proptosis and Clinical Activity Score in patients with active TED, and this patient's worsening symptoms with diplopia and exophthalmos indicate active disease 2.
• The standard dosing regimen remains 10 mg/kg for the initial infusion followed by 20 mg/kg every three weeks for 7 additional infusions, totaling 8 infusions over 24 weeks 1.

Evidence Supporting Retreatment

High-Quality Clinical Trial Data on Retreatment

• The OPTIC-X study (2022) demonstrated that patients who experienced disease flare after initial teprotumumab treatment showed 62.5% response rate when retreated, with mean proptosis reduction of 1.9 mm from retreatment baseline 3.
• Among patients who flared after initial treatment, retreatment resulted in maintained responses in 90.6% for proptosis, 95.2% for CAS, and 85.7% for diplopia at 48-week follow-up 3.
• The OPTIC-X study found no new safety signals with retreatment, though mild hearing impairment events were noted (4 during first course, 2 reoccurred after retreatment) 3.

Long-Term Efficacy Data

• A 2024 pooled analysis of 112 patients across three clinical trials showed that at week 72 (51 weeks post-treatment), 91.2% maintained CAS response, 89.5% maintained composite outcome response, and 67.9% maintained proptosis response 4.
• Only 17.9% of patients required additional TED therapy over 99 weeks following teprotumumab, indicating durable response in the majority 4.

Recalcitrant Disease Evidence

• A 2024 multicenter study of 66 patients with recalcitrant TED (mean disease duration 57.8 months) who failed prior conventional therapy showed proptosis response of 85.9%, CAS response of 93.8%, and diplopia response of 69.1% with teprotumumab 5.
• These response rates in recalcitrant patients were similar to treatment-naïve patients from pivotal trials, supporting retreatment efficacy 5.

Critical Assessment Requirements Before Retreatment

Mandatory Pre-Treatment Evaluation

• Assess for pre-existing hearing loss before retreatment and counsel the patient about hearing risk, as the American Academy of Ophthalmology guidelines note teprotumumab should be considered with caution in patients with pre-existing hearing loss 2.
• Confirm thyroid function tests are controlled, as recommended by ophthalmology specialists 2.
• Document current Clinical Activity Score (CAS) to establish baseline for treatment response monitoring; a CAS ≥3 indicates active inflammation, and CAS ≥5 with documented symptoms demonstrates active moderate-to-severe disease 2.

Disease Activity Documentation

• Measure and document current proptosis by exophthalmometry to establish baseline and track response 6.
• Assess diplopia using standardized grading (Gorman scale) to quantify baseline severity 3.
• Screen for optic neuropathy with visual acuity, color vision, visual fields, pupillary exam, and fundus examination 6.
• Consider orbital imaging (CT or MRI) to evaluate extraocular muscle size and orbital fat volume, which teprotumumab has been shown to reduce 2.

Treatment Algorithm for This Patient

Step 1: Confirm Disease Flare

• Document ≥2 mm increase in proptosis from post-treatment baseline, OR ≥2-point increase in CAS, OR worsening diplopia 3.
• This patient meets criteria with worsening diplopia and exophthalmos.

Step 2: Complete Pre-Treatment Safety Assessment

• Perform audiometric testing to establish baseline hearing function 2, 3.
• Verify thyroid function is controlled (euthyroid state preferred) 2.
• Rule out compressive optic neuropathy requiring urgent intervention 6.

Step 3: Initiate Retreatment

• Administer standard 8-infusion protocol: 10 mg/kg initial dose, then 20 mg/kg every 3 weeks for 7 additional infusions 1.
• Infuse over 90 minutes for first two infusions; if well tolerated, subsequent infusions can be reduced to 60 minutes 1.

Step 4: Monitor Response and Safety

• Assess proptosis, CAS, and diplopia at regular intervals during treatment 3.
• Monitor for hearing changes throughout treatment course 3.
• Expected response timeline: improvements typically observed by week 24 with durability extending to week 72 4.

Common Pitfalls and Caveats

Prior Orbital Decompression Surgery

• Patients with prior orbital decompression show significantly decreased diplopia response (46.7% vs. 77.5%) and proptosis response (75.0% vs. 90.9%) compared to surgery-naïve patients 5.
• This patient's surgical history should be reviewed; if prior decompression was performed, counsel about potentially reduced but still meaningful response rates.

Hearing Risk Management

• Hearing impairment is the most significant safety concern, with some events recurring upon retreatment 3.
• Establish baseline audiometry and monitor throughout treatment.
• Counsel patient that hearing changes may be permanent in rare cases.

Disease Duration Considerations

• The OPTIC-X study showed patients with longer disease duration (median 12.9 months) responded similarly to those treated earlier (6.3 months), indicating disease chronicity does not preclude retreatment benefit 3.
• A case report demonstrated efficacy even in a patient with 16-year disease history and prior orbital decompression 7.

Timing of Retreatment

• No specific waiting period is mandated between treatment courses based on FDA labeling 1.
• Clinical judgment should guide timing based on disease activity and severity of symptoms.

Alternative Considerations if Retreatment Fails

• If inadequate response to retreatment occurs, consider orbital decompression, high-dose steroids, or radiation treatment for severe proptosis or optic neuropathy 6.
• Strabismus surgery may be needed for persistent diplopia, ideally delayed until disease is stable for 6 months, though earlier intervention can be considered in select cases 6.