Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Thyroid Eye Disease
Treatment: Tepezza
The insurer denied: Tepezza
The denial is overturned.

The patient is an adult female with thyroid eye disease for whom coverage of a second course of Tepezza is the subject of review. The patient was previously successfully treated with Tepezza last year. The effect lasted for about 6 months after which the patient began experiencing disease flare with recurrent eyelid edema, redness of the eyelids, orbital pain with eye movements and intermittent diplopia. Coverage was previously denied per policy which will authorize only a maximum of 8 doses per lifetime. 
Upon appeal, the requested for Tepezza is identified as urgent with the patient's Clinical Activity Score (CAS) identified having increased as high as 8/10 with increased proptosis, edema of her eyelids, chemosis, enlarged caruncle, orbital pain, and constant vertical diplopia. Reportedly, the patient received several urgent doses of a second course of Tepezza, but insurance would not approve completion of the course. A note earlier this month documents diplopia as not as bad as before the patient had 2 doses of Tepezza. Clinical Activity Score had decreased to 5. Continued treatment was recommended. While waiting for the appeal, a course of weekly intravenous steroids was prescribed.

The requested second course of Tepezza is established as medically necessary.

Douglas et al. evaluated the safety and efficacy of teprotumumab in patients with thyroid eye disease (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 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, subjective diplopia, and quality-of-life. Thirty-three of 37 placebo-treated OPTIC patients (89.2 percent [%]) became proptosis responders (mean  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 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 mm from OPTIC baseline, and 2 discontinued treatment 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 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 thyroid eye disease (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. 
As there is a growing body of evidence for the efficacy of retreatment with Tepezza in patients experiencing flare following prior Tepezza treatment, and as this patient's symptoms previously improved with Tepezza but then flared to a CAS of 8, medical necessity of Tepezza is established as among standard of care. The request is clinically appropriate, required for direct care or treatment of management of thyroid eye disease, and the condition would be adversely affected if it were not provided.