Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Vision/Other/Moderate to Severe Thyroid Eye Disease
Treatment: Pharmacy/Prescription Drugs/Tepezza
The health plan denied the requested medication, Tepezza, as not medically necessary. The health plan's determination is overturned.

This is a woman with thyroid disease status post thyroidectomy, now with Grave's Disease including bilateral retroorbital pain, tearing, orbital fat hypertrophy, proptosis, an overall clinical activity score (CAS) of 4 and intermittent diplopia. Her oculoplastic surgeon recommended that she be treated with Tepezza/Teprotumumab.
At issue is the medical necessity for the requested medication, Tepezza.

The health plan's determination of medical necessity is overturned, in whole.

Yes, Tepezza is medically necessary. This patient meets the criteria for inclusion in the clinical trials of this medication which demonstrated good efficacy for patients similar to her with resolution of their CAS scores, proptosis, and Graves symptoms. She is a good candidate for the medication.
Graves' orbitopathy or thyroid eye disease (TED) is an autoimmune disease characterized by proliferation of orbital fibroblasts which release glycosaminoglycans and result in increased extraocular muscle size and orbital fat volume. In Graves' disease, thyroid stimulating immunoglobulins (TSI or GD-IgG) stimulate the thyroid stimulating hormone receptor (TSHR) or thyrotropin receptor leading to increased levels of thyroid hormone. A second receptor, the IGF-1R (Insulin-like Growth Factor Receptor-1), has been shown to play a significant role. Teprotumumab is a fully human monoclonal antibody that binds to the ligand binding extracellular alpha subunit of the IGF-1R. Teprotumumab reduces levels of the TSHR and IGF-1R on fibrocytes.
Smith et al conducted a multi-center, randomized, double-masked, placebo-controlled phase II clinical trial of 88 patients with active moderate to severe TED. Enrolled patients were required to have active disease with clinical activity scores (CAS) of 4 or more for no more than 9 months. A response had been defined as >= 2-point decrease in CAS and >= 2mm (millimeter) decrease in proptosis without worsening in the fellow eye, at week 24, the Teprotumumab group had a significantly higher response rate of 69%, compared to 20% for the placebo group. The Teprotumumab group also had significant improvements in secondary outcomes, including proptosis, clinical activity score, subjective diplopia, and quality of life
Douglas et al conducted a multi-center, randomized, double-masked, placebo-controlled phase III clinical trial, the OPTIC trial, of 83 patients with active moderate to severe TED. the primary outcome was simplified to a proptosis response defined as a >= 2mm reduction of proptosis without an increase of >= 2mm in the fellow eye. The Teprotumumab group also had a greater overall response, more patients with CAS score reduction to 0 or 1, greater mean change in proptosis, greater diplopia response, and greater mean change in quality of life.
As noted, this patient had a CAS score of 4. In addition, she had diplopia, conjunctival erythema and orbital fat hypertrophy on her initial exam. These criteria match the inclusion criteria for the randomized control trials noted above. The denial stated that the patient didn't have diplopia, however, this is not an inclusion criteria for any of the trials. Therefore, the best interest of the patient was not met.
The patient meets all the inclusion criteria demonstrated in the literature and noted in patients who had a good response to Tepezza/Teprotumumab. The clinical trials do not use diplopia as a primary end point, though they do note improvement in diplopia as a secondary end point. Further, follow up documentation does note that she has complaints of diplopia. Therefore, she meets all the plan's criteria as well.