Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Thyroid eye disease. 
Treatment: Teprotumumab (Tepezza). 
The insurer denied Teprotumumab (Tepezza). 
The determination is overturned. 

This is a patient with thyroid eye disease (TED) for whom coverage of an additional course of Tepezza is the subject of review. Coverage was previously denied as the requested dose exceeds the maximum recommended dosing of up to 8 total lifetime infusions. The patient previously received 8 doses. The patient is now experiencing a flare of symptoms with spontaneous orbital pain, eyelid swelling, conjunctival redness, chemosis, inflammation of the caruncle, lid retraction corneal exposure, dry eye, soft tissue involvement, mild hearing loss and proptosis. A Clinical Activity Score (CAS) was 5. At issue is the medical necessity of Teprotumumab (Tepezza).

Douglas et al. evaluated the safety and efficacy of teprotumumab in patients with TED who were nonresponsive or who experienced a disease flare. The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) was a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. OPTIC nonresponders or those who flared (2-millimeter (mm) increase in proptosis, 2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. The main outcome measures included proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean plus/minus () standard deviation, -3.5  1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced a flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9  1.2 mm from OPTIC-X baseline and 3.3  0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during first course of treatment, and 2 events reoccurred after re-treatment. The authors concluded that patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. 
Therefore, as there is a growing body of evidence for the efficacy of retreatment with Tepezza in patients with chronic TED experiencing a flare following prior effective with Tepezza treatment, the medical necessity for re-treatment is established for this patient among the standard of care.