Is a second course of Tepezza (teprotumumab-trbw) medically indicated for a patient with Thyroid Eye Disease (TED) and a Clinical Activity Score (CAS) of 5?

Medical Necessity Determination for Second Course of Tepezza

Based on current evidence, a second course of teprotumumab is medically indicated for this patient with active TED flare, despite the Aetna policy exclusion, as the clinical benefits in preventing irreversible complications and improving quality of life outweigh policy restrictions when disease reactivation is documented.

Critical Analysis of the Authorization Request

Disease Severity Assessment - Key Issue

The CAS of 5 meets the threshold for moderate-to-severe active disease. The Clinical Activity Score ranges from 0-7, with scores ≥3 indicating active inflammation 1. This patient's CAS of 5, combined with documented pain, proptosis, lid swelling, and ocular dryness, clearly demonstrates active moderate-to-severe disease that satisfies medical necessity criteria 2.

• Active TED with CAS ≥4 was the inclusion criterion in pivotal trials showing significant benefit 3, 4
• The American Academy of Ophthalmology guidelines recognize teprotumumab reduces proptosis and CAS in patients with active TED 1
• Disease activity, not just severity, is the critical determinant for treatment eligibility 2

The Second Course Controversy

The most significant barrier is the Aetna policy explicitly excluding repeat courses of Tepezza, which directly conflicts with emerging clinical evidence supporting retreatment.

Evidence Supporting Retreatment:

• The OPTIC-X study (2022) demonstrated that patients who flared after initial teprotumumab treatment showed 62.5% response rate to retreatment, with mean proptosis reduction of 3.3 mm from original baseline 5
• Patients with disease reactivation (≥2-mm increase in proptosis or ≥2-point increase in CAS) who were retreated maintained responses in 90.6% for proptosis and 95.2% for CAS at 48-week follow-up 5
• The pooled analysis of two randomized trials showed sustained responses at 51 weeks post-treatment in 67% for proptosis and 69% for diplopia, but acknowledged that some patients experience flare requiring additional therapy 4

Clinical Context for This Patient:

• This patient demonstrated "significant clinical improvement" after the 2021 course, establishing treatment responsiveness 5
• Current presentation shows clear disease reactivation with increased symptoms and CAS of 5
• The ophthalmologist's impression explicitly recommends second course if thyroid function tests are controlled
• Time interval since first course (approximately 3 years) represents genuine disease flare, not treatment failure 5

Longer Disease Duration Consideration

The patient's disease duration from initial diagnosis is not explicitly stated but appears to be at least 3+ years given the 2021 treatment course. The OPTIC-X study specifically addressed this concern:

• Patients with median TED duration of 12.9 months (versus 6.3 months in original OPTIC trial) showed equivalent response rates of 89.2% when treated with teprotumumab 5
• Longer disease duration did not diminish treatment efficacy 5
• This directly contradicts the notion that teprotumumab only works in early disease 5

Safety Considerations for Retreatment

No new safety signals were identified in retreatment studies, though hearing impairment requires specific monitoring:

• Mild hearing impairment occurred in 4 events during first course and 2 events reoccurred after retreatment in OPTIC-X 5
• The American Academy of Ophthalmology guidelines note teprotumumab should be considered with caution in patients with pre-existing hearing loss 1
• Other adverse events (hyperglycemia, muscle spasms, nausea, diarrhea) were predominantly mild-to-moderate (94% grade 1-2) 4
• Critical caveat: Assess for pre-existing hearing loss before retreatment and counsel patient about hearing risk 1, 5

Outcomes That Matter Most

Morbidity Prevention:

• Without treatment, active TED with CAS of 5 risks progression to compressive optic neuropathy (vision-threatening) and irreversible fibrotic changes 2
• Teprotumumab reduces extraocular muscle size and orbital fat volume, preventing mechanical complications 1
• The recalcitrant TED study showed 85.9% proptosis response and 93.8% CAS response even in treatment-resistant cases 6

Quality of Life:

• Integrated analysis showed moderate-to-large improvements in GO-QOL scores (19 vs 6 for placebo, p<0.0001) that were maintained during follow-up 4
• Diplopia improvement occurred in 68% of patients in pivotal trials, directly impacting daily function 3
• The patient's prior positive response in 2021 suggests high likelihood of QOL benefit with retreatment 5

Recommendation Algorithm

Approve the second course of teprotumumab (8 infusions) based on:

1. Active disease confirmed: CAS of 5 with documented symptoms (pain, proptosis, lid swelling, dryness) 1, 2
2. Disease reactivation documented: Clear flare after previous successful treatment course 5
3. Prior treatment response: Patient showed "significant clinical improvement" in 2021, predicting retreatment success 5
4. Specialist recommendation: Ophthalmologist explicitly recommends second course with TFT control 1
5. Evidence-based efficacy: OPTIC-X study validates retreatment with 62.5% response in flare patients 5

Required Pre-Treatment Steps:

• Confirm thyroid function tests are controlled (per ophthalmologist's recommendation) 1
• Perform baseline audiometry to document hearing status before retreatment 1, 5
• Screen for inflammatory bowel disease (relative contraindication) and pregnancy (absolute contraindication) 1
• Document baseline proptosis measurements and CAS for response monitoring 3

Common Pitfall to Avoid:

Do not deny based solely on Aetna's blanket exclusion of repeat courses. This policy predates the OPTIC-X retreatment data (2022) and the recalcitrant TED study (2024) that demonstrate clear benefit in disease reactivation 6, 5. Medical necessity should be determined by clinical evidence and patient-specific factors, not outdated administrative policies that conflict with current medical literature.