Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Thyroid Eye Disease. 
Treatment: Tepezza 500MG (milligrams) Injection. 
The insurer denied: Tepezza 500MG (milligrams) Injection. 
The denial is overturned. 

The patient is an adult female for whom coverage of retreatment with Tepezza is the subject of review. Coverage was previously denied by the health plan, as the request exceeds the maximum recommended treatment duration of 8 doses for the diagnosis of thyroid eye disease. Upon appeal, the provider cites the Open-Label Clinical Extension Study (OPTIC-X) trial, which supports additional teprotumumab therapy for patients with thyroid eye disease who have experienced insufficient initial response or flare, as in this case. The patient has worsening proptosis, her ductions are limited, and her Clinical Activity Score (CAS) is reported as 5, which is worse than prior to her first Tepezza treatment. In addition to eyelid swelling, conjunctivla injection, chemosis, caruncular inflammation and eye pain at rest, the patient has developed diplopia that is worsening, as well as recurrent eyelid retraction. 

The requested Tepezza is medically necessary. 

Douglas et al. evaluated the safety and efficacy of teprotumumab in patients with TED (thyroid eye disease) who were nonresponsive or who experienced a disease flare. The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an 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 non-responders or those who flared (2-millimeter 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. Main outcome measures included proptosis response and safety. Secondary outcomes included proptosis, CAS (clinical activity score), subjective diplopia, and quality-of-life. Thirty-three of 37 placebo-treated OPTIC patients (89.2%[percent]) became proptosis responders (mean [plus,minus] standard deviation, -3.5  1.7 millimeters) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS (clinical activity score) 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 (thyroid eye disease) 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 millimeter from OPTIC baseline, and 2 discontinued treatments early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9  1.2 millimeters from OPTIC-X baseline and 3.3  0.7 millimeters 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 (thyroid eye disease) 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 experiencing flare following prior Tepezza treatment as in this patient's case, medical necessity is established as among standard of care within the ophthalmology community.