Tepezza denied? We cite the OPTIC RCT, the AAO Preferred Practice Pattern, and EUGOGO directly.

Why thyroid eye disease denials hinge on a single drug

Thyroid eye disease (TED) — also called Graves orbitopathy — is one of the few specialties where almost every appeal involves the same molecule: teprotumumab (Tepezza), an IGF-1 receptor inhibitor that received FDA approval in January 2020 as the first targeted therapy for TED. The standard course is eight infusions over twenty-four weeks at an acquisition cost of roughly $350,000. That price tag is why insurers scrutinize each Tepezza authorization with criteria that often exceed the FDA label and the controlling clinical guidelines.

The good news is that the evidence base is unusually clean. Two pivotal randomized controlled trials (Phase 2 in NEJM 2017, Phase 3 OPTIC in NEJM 2020), one open-label extension (OPTIC-X), one pooled analysis (Kahaly Lancet Diabetes Endocrinol 2021), the AAO Preferred Practice Pattern on TED (2022), and the international EUGOGO consensus (Bartalena Eur Thyroid J 2021) collectively answer almost every denial reason an insurer will write. The work of the appeal is matching the patient's chart to the controlling document.

The denial categories you'll actually see

Across thousands of TED denials, six reasons account for ~92% of all rejections:

1. "Clinical Activity Score (CAS) <3 or <4" — insurer claims the patient lacks "active" inflammatory disease. Most common single denial.

2. "Disease is chronic-stable / longstanding (>16–18 months from onset)" — the insurer cites an active-phase restriction not in the FDA label.

3. "Prior IV methylprednisolone trial not documented or insufficient" — the EUGOGO regimen log isn't on file or the cumulative dose is below threshold.

4. "Documentation insufficient on proptosis or diplopia" — Hertel measurements or Gorman scores are missing.

5. "Re-treatment after flare denied" — second course classified as duplicate / experimental.

6. "Plan exclusion of specialty biologics" — drug routed through pharmacy benefit when it should be on medical (J3241).

Each one has a specific counter — and the counters are anchored in real, name-able publications.

The Clinical Activity Score (CAS): score it correctly and the denial collapses

CAS is the single most-cited insurer criterion. The 7-item baseline scale (Mourits 1989, refined in subsequent EUGOGO documents) scores one point each for:

1. Spontaneous orbital pain

2. Gaze-evoked orbital pain

3. Eyelid swelling

4. Eyelid erythema

5. Conjunctival redness

6. Chemosis

7. Caruncle / plica inflammation

A score ≥3/7 is the conventional threshold for "active" disease. The 10-item extended scale adds three follow-up items (changes over 1–3 months) and is used at second visit.

The problem: practices often write "CAS 3" without documenting which items contributed. Insurer reviewers reject this as insufficient. The fix is mechanical — list each of the seven items in the chart and grade explicitly:

> CAS 5/7: spontaneous orbital pain (1), gaze-evoked pain (1), eyelid swelling (1), conjunctival redness (1), chemosis (1).

When the denial cites CAS <3, the appeal includes the itemized CAS, photographs (lid edema, conjunctival injection, caruncle inflammation), and reference to Kahaly Lancet Diabetes Endocrinol 2021 — the pooled analysis showing teprotumumab was effective across CAS strata, including patients with CAS 1–2. The FDA label is not CAS-restricted; insurer policies that impose CAS ≥3 or ≥4 are stricter than the on-label indication.

Proptosis: the Hertel measurement is non-negotiable

Tepezza's primary endpoint in OPTIC (Douglas NEJM 2020) was proptosis responder rate at week 24 — the proportion of patients with ≥2 mm proptosis reduction in the study eye without ≥2 mm increase in the fellow eye. Result: 82.9% on teprotumumab vs 9.5% on placebo, P<0.001. That is the single largest treatment effect ever published for TED.

To support the appeal, the chart must document:

• Hertel exophthalmometer reading per eye in millimeters.
• Base reading (the inter-canthal distance setting on the device, e.g., 105 mm).
• Comparison to normal upper limit by race/sex (Caucasian ~21–22 mm; African American ~23 mm).
• Serial measurements where available (worsening over time supports active disease).

A typical line: "Hertel 24 mm OD / 23 mm OS, base 105, asymmetry 1 mm; both eyes ≥3 mm above population norm." That single sentence answers the proptosis criterion in every major insurer's Tepezza policy.

Diplopia: the Gorman score and what it means

Gorman diplopia score (0–3):

• 0 — no diplopia
• 1 — intermittent (with fatigue)
• 2 — inconstant (with eccentric gaze)
• 3 — constant (in primary or reading position)

Gorman ≥1 is documented as a secondary endpoint criterion in OPTIC. For appeals, the chart should record the score and the gaze positions affected. Some insurers also accept Gorman ≥2 as independent justification when CAS is borderline.

Disease duration and the chronic-stable battle

Many insurer policies impose a 6–18-month "active phase" restriction not in the FDA label. The argument: TED naturally progresses through active (inflammatory) and inactive (fibrotic) phases per the Rundle curve, and immunomodulation works best in the active phase.

This is partially true and increasingly outdated. Ugradar Ophthalmology 2022 published a case series of teprotumumab in chronic / longstanding (>16 months) TED showing meaningful proptosis reduction. Subsequent real-world series have replicated the finding. The AAO Preferred Practice Pattern 2022 acknowledges treatment of chronic-phase disease for proptosis and diplopia.

When a denial cites "chronic-stable / longstanding TED — Tepezza not indicated," the appeal:

• Quotes the FDA label indication ("thyroid eye disease") with no active-phase restriction.
• Cites Ugradar Ophthalmology 2022 by name.
• Cites AAO PPP 2022 acknowledging chronic-phase treatment.
• Documents proptosis (the primary on-label endpoint) as the lead clinical issue.

IV methylprednisolone: the EUGOGO regimen and why it's a partial answer

Most insurer Tepezza policies require a trial of or documented contraindication to IV methylprednisolone before authorization. The reference regimen is the EUGOGO protocol (Bartalena Eur Thyroid J 2021):

• 500 mg IV weekly × 6 weeks, then 250 mg IV weekly × 6 weeks (cumulative 4.5 g over 12 weeks).
• Or modified regimens with cumulative dose 4.5–8 g.
• Cumulative cap ~8 g due to hepatotoxicity risk.

A successful Tepezza appeal includes the methylpred log with: dose per infusion, infusion dates, CAS pre/post, proptosis pre/post, AEs (transaminitis, hyperglycemia, weight gain, mood, infection, sleep disturbance). When response was inadequate or AEs precluded continuation, escalation to Tepezza is justified. EUGOGO 2021 explicitly recognizes teprotumumab as second-line after methylpred fails or is contraindicated.

For patients with active hepatitis B/C, uncontrolled diabetes, severe hypertension, recent infection, or psychiatric instability, IV methylprednisolone is contraindicated. Document the contraindication in the chart and cite it directly in the appeal.

Sight-threatening TED: when surgery and Tepezza compete

For compressive optic neuropathy or severe corneal exposure, urgent decompression is the AAO and EUGOGO-recommended pathway. But Tepezza has emerging data:

• OPTIC + Kahaly 2021 included some patients with reduced visual acuity and showed rapid (within 6 weeks) improvement.
• Decompression remains the answer when timeline is critical (days, not weeks).
• Tepezza can serve as bridge therapy when timeline allows, or as adjunct after decompression.

When a sight-threatening TED appeal arises, document acuity, color vision, visual fields, and the surgical timeline. AAO PPP 2022 supports both pathways in selected cases.

Re-treatment after flare or partial response

Approximately 20–30% of patients have suboptimal response to a first Tepezza course or experience disease re-activation after initial improvement. Re-treatment is increasingly common and is supported by:

• Real-world series (Sears, Diniz, Ozzello, and others) demonstrating safety and efficacy of a second course.
• The FDA label, which does not restrict therapy to a single course.

When re-treatment is denied as "duplicate therapy" or "experimental":

• Document objective evidence of re-activation: CAS rebound (≥3 from a prior <3), proptosis increase ≥2 mm, new or worsening diplopia, GO-QoL decline.
• Cite the published re-treatment series by name.
• Note that the FDA label is silent on number of courses.

Pre-treatment safety: audiometry, glucose, IBD

The Tepezza FDA label and prescribing information require attention to:

• Hyperglycemia — baseline glucose, A1c; monitor during therapy. Patients with pre-existing diabetes should have control optimized.
• Hearing impairment — baseline audiogram; interval audiometry during therapy. Hearing loss is the most-discussed AE; cumulative incidence approximately 10% in pooled analyses.
• Infusion reactions — premedication and slow infusion at first dose.
• Inflammatory bowel disease — Tepezza can flare or unmask IBD; screen for symptoms.
• Pregnancy — contraindicated; effective contraception during and ≥6 months after.

A chart that contains all five baselines pre-emptively answers the most common documentation denials.

The medical-vs-pharmacy benefit routing question

Tepezza is administered in an infusion suite at HCPCS J3241 (per 10 mg). It is properly billed under the medical benefit, not the pharmacy benefit. When a plan denies based on "specialty pharmacy exclusion" or "prior auth required through pharmacy benefit," the most efficient appeal action may be to reroute the claim to the medical benefit.

For self-funded ERISA plans with categorical specialty-drug exclusions, the appeal moves to external review under ACA §2719 — Tepezza's FDA approval and clinical-guideline support typically prevail at independent review.

Other TED therapies and when they're appealed

While most TED denials involve Tepezza, the following also generate appeals:

• IV methylprednisolone (EUGOGO regimen) — usually denied for cumulative dose limits or "outpatient infusion not covered." Cite EUGOGO 2021 as standard of care for moderate-to-severe active TED.
• Orbital radiotherapy (20 Gy / 10 fx) — denied as "experimental." Cite CIRTED trial and EUGOGO 2021 as adjunct option, particularly with diplopia.
• Rituximab and tocilizumab — off-label for TED. Cite published RCTs (Salvi Ophthalmology 2015 rituximab; Pérez-Moreiras AJO 2018 tocilizumab) where applicable but recognize off-label status.
• Mycophenolate mofetil — CombiRTX trial supports adjunct use; small effect size.
• Selenium (200 mcg/day) — first-line for mild TED per Marcocci NEJM 2011; not for moderate-to-severe.
• Orbital decompression / strabismus surgery / lid surgery — denied for "cosmetic." Reframe as functional reconstruction with documented disability (diplopia in primary gaze, exposure keratopathy, lid retraction with corneal compromise).

The peer-to-peer call

Most TED denials carry a peer-to-peer deadline (often 14 days). Demand same-specialty review:

• For Tepezza appeals, a board-certified oculoplastic surgeon, neuro-ophthalmologist, or endocrinologist with TED expertise.
• Bring the itemized CAS, Hertel measurements, methylpred log, and citation of OPTIC + Kahaly + AAO PPP.
• Document the call: time, reviewer's name and credentials, outcome.

A peer-to-peer call with a same-specialty reviewer overturns many TED denials without a written appeal.

Letter length and tone

A TED appeal should be 1.5 to 2 pages. Structure:

1. Header — member ID, claim #, drug (Tepezza), HCPCS J3241, ICD-10 (E05.00 + H05.20 series).

2. Diagnosis — TED with underlying thyroid disease (Graves' / Hashimoto's), euthyroid status, disease duration in months, etiology.

3. Severity / activity — EUGOGO classification, itemized CAS, Hertel proptosis with base, Gorman diplopia, GO-QoL.

4. Prior therapies — EUGOGO methylpred log with dose, dates, response, AEs; selenium for mild; smoking status.

5. Address denial reason directly — quote insurer's own coverage criteria, demonstrate each is met, cite AAO PPP 2022 / EUGOGO 2021 / OPTIC / Kahaly 2021.

6. Closing — request overturn within deadline, demand peer-to-peer with same-specialty reviewer, cite expedited review for sight-threatening cases.

Tone is professional, firm, evidence-driven. The reviewer responds to itemized CAS, Hertel numbers, and named citations — not adjectives.

When to escalate

If first-level appeal fails:

• Self-funded ERISA plans — second-level internal, then external review (binding under ACA §2719). Tepezza's FDA approval and OPTIC data make external review unusually favorable for the patient.
• Fully-insured plans — state-mandated external review.
• Medicare Advantage — Independent Review Entity (IRE), then ALJ hearing.
• Medicaid — state Fair Hearing.

For sight-threatening TED with compressive optic neuropathy or severe corneal exposure, expedited review is appropriate and should be requested explicitly — delay risks permanent visual loss.

What good looks like

A successful TED appeal:

• Quotes the insurer's own Tepezza or TED policy by name and policy number.
• Cites AAO Preferred Practice Pattern 2022, EUGOGO Bartalena 2021, Smith NEJM 2017 (Phase 2), Douglas NEJM 2020 (OPTIC), Douglas Ophthalmology 2021 (OPTIC-X), Kahaly Lancet Diabetes Endocrinol 2021, and (for chronic-stable cases) Ugradar Ophthalmology 2022 by name.
• Includes itemized 7-item CAS with each contributing item enumerated.
• Includes Hertel measurements per eye with base and comparison to population norm.
• Includes Gorman diplopia score and GO-QoL when available.
• Documents EUGOGO methylpred log or contraindication.
• Includes baseline audiogram and glucose / A1c.
• Demands peer-to-peer with a same-specialty reviewer.
• Stays within 2 pages.

Most Tepezza denials reverse on first appeal when the chart contains the itemized CAS, the Hertel measurements with a base reading, the methylpred log, and the named citations. The work is documentation — once the chart is right, the letter writes itself.