Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Thyroid Eye Disease (graves ophthalmopathy)
Treatment: Tepezza SMG (Pre-Service)
The insurer denied the Tepezza SMG (Pre-Service).
The denial is upheld. 

The patient is a female with thyroid eye disease for whom coverage of Tepezza is the subject of review. Coverage was previously denied as the patient was identified as having mild thyroid eye disease with a clinical activity score (CAS) of 3, while the plan approved criteria does not allow for coverage of Tepezza for thyroid eye disease unless patients have active disease with a CAS greater than or equal to 4.

Upon appeal, the provider confirms a CAS of 3 noting the following ocular complications, which negatively impact her everyday activities, including ptopsosis (Hertel measurements: 100 mm [millimeters] base, 20 mm right eye and 21 mm left eye), severe, constant pain behind her eyes, significant periocular swelling in the morning and conjunctival injection. The patient is reportedly compliant with methimazole treatment under the care of an endocrinologist for management of Graves' Disease.

The provider also notes that The European Group on Graves' Orbitopathy (EUGOGO) classifies patients with a CAS score of at least 3 as having active disease, and nowhere within the FDA (United States Food and Drug Administration)-approved prescribing information does it limit use to patients with a CAS of 4 or greater.

An exam documents the patient having been diagnosed with Graves' disease previously and having been on methimazole on and off since then. Thyroid function tests were last checked a year ago. The patient noted significant periocular swelling in the mornings and feels a constant pressure headache and pain behind her eyes without diplopia. On exam, vision was 20/20-1 OU (both eyes). Exophthalmos was noted with Hertels measuring 20 mm OD (right eye) and 21 mm OS (left eye) on a base of 100 mm. Mild eyelid edema was present along with trace conjunctival injection. No corneal abnormalities were noted. The patient was diagnosed with mild Graves' disease with a clinical activity score of 3. The provider advised the patient that she would likely benefit from treatment with Tepezza.

No, the treatment with Tepezza is not established as medically necessary per standard of care.

Thyroid eye disease (TED) is an autoimmune inflammatory disorder involving the soft tissues of the orbit. The classic clinical findings include eyelid retraction, exophthalmos, extraocular muscle restriction, and optic nerve dysfunction (all of which this patient has). Additional exam features are eyelid lag (von Graefe sign), lagophthalmos, conjunctival hyperemia over the horizontal rectus muscle insertions, resistance to globe retropulsion, and superior limbic keratoconjunctivitis. During the course of TED, eyelid retraction occurs in 90% of patients, with exophthalmos present in 60%. The combination of these features can lead to scleral show and exposure keratitis. Commonly associated symptoms include ocular pain, dry eyes, tearing, photophobia, and blurred vision. Diplopia from a restrictive myopathy presents in 40%. Approximately 20% of TED patients undergo surgical treatment, including orbital decompression (7%), strabismus surgery (9%), and eyelid surgery (13%).

Current medical therapies for thyroid-associated ophthalmopathy primarily consist of glucocorticoids, have limited efficacy, and present safety concerns with continued use. Rituximab, a monoclonal antibody that targets CD-20 (B-lymphocyte antigen CD20) on B-cells has been used experimentally with some promising results. Orbital radiation can be used alone or in conjunction with cortisosteroids, but has radiation retinopathy as a side effect. Ultimately, orbital decompression and/or strabismus surgery may be needed.

Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy.

The authors concluded that, in patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the CAS.

Tepezza was FD-approved for the treatment of Thyroid Eye Disease over a year ago.

Medicare is not currently identified as having a National Coverage Determination (NCD) for Tepezza (teprotumumab-trbw). So, Local Coverage Determinations (LCDs) do not currently exist. Per standard of care, most insurers base indication for treatment with Tepezza on the OPTIC (Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study) trials where patients were required to have active, moderate to severe thyroid eye disease with significant symptoms and where patients were also required to have a clinical activity score (CAS) greater than or equal to 4 and symptoms less than nine months from the onset of thyroid eye disease. In these studies, all patients were euthyroid or with mild hypothyroidism or hyperthyroidism, defined as free thyroxine (T4) and free triiodothyronine (T3) levels less than 50% above or below the normal limits for the testing laboratory.

In this case, the patient is described as having active yet mild thyroid eye disease with exophthalmometry readings in the normal range (normal values are < 20 mm to < 22 mm) and a Clinical Activity Score of 3. The patient is being treated with methimazole, but there is no recent documentation of the patient being euthyroid or with mild hypothyroidism or hyperthyroidism according to the criteria above. Therefore, the requested Tepezza is not established as medically necessary per standard of care.