Anthem Blue Cross California Tepezza (teprotumumab-trbw) Form

Overview Clinical criteria Overview Coding Document history References This document addresses the use of Tepezza (teprotumumab-trbw). Tepezza is a fully human insulin-like growth factor-1 (IgG1) monoclonal antibody that competitively inhibits the IgG1 receptor. It is used to treat Thyroid Eye Disease (TED), otherwise known as Graves’ Orbitopathy or Graves’ Ophthalmopathy. Thyroid Eye Disease is a rare vision-threatening autoimmune disease. It is associated with dry or irritated eyes, outward bulging of eyes (proptosis), double vision (diplopia), and optic nerve compression. TED is often associated with Graves’ disease, the most common cause of hyperthyroidism and develops in roughly 40% of patients with Graves’ disease. Therefore, classic findings would include orbitopathy in the setting of current or past Graves’ hyperthyroidism (low TSH, high free thyroxine [T4] and/or triiodothyronine [T3]). However, hyperthyroidism is not directly linked to TED; and about 10% of TED patients have a normally functioning thyroid. This “euthyroid” Graves’ disease is still characterized by high serum thyroid autoantibody concentrations, which contribute to the development of TED. The natural history of the disease is variable and may include a period of rapid deterioration followed by stabilization, or individuals may experience exacerbations and remissions. Most patients have self-limiting mild forms of the disease where lifestyle modifications (smoking cessation, local therapies such as artificial tears, and elevating the head of the bed to decrease swelling) are warranted. The 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis recommend that euthyroidism be achieved and maintained in hyperthyroid patients with TED or risk factors for the development of orbitopathy. Surgery and antithyroid medications are the preferred treatments for Graves’ Disease; no recommendation is provided for the treatment of TED itself. The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Guidelines for the Management of Graves’ Orbitopathy recommends high-dose intravenous glucocorticoids be considered as first-line therapy for moderate-to-severe and active GO. Second-line treatment options include a subsequent course of intravenous glucocorticoids, oral corticosteroids combined with either cyclosporine or azathioprine, orbital radiotherapy combined with oral or intravenous glucocorticoids, teprotumumab (Tepezza), rituximab, or tocilizumab. However, Tepezza is not approved for use in Europe. Surgical options for TED include orbital decompression and muscle surgery to correct diplopia. Tepezza has not been directly compared to corticosteroid therapy in the treatment of TED. Tepezza is the first FDA approved agent to treat TED and its mechanism of action is not fully known. Signaling by overexpressed Insulin-like growth factor 1 receptors (IGF-1R) leads to hyaluronan accumulation and cytokine expression resulting in inflammation and extraocular tissue expansion. Tepezza was evaluated in two trials of similar design (Smith 2017, Douglas 2019 [OPTIC]). Trials required participants to have Graves’ disease with active TED with a clinical activity score ≥ 4 (see table below). Patients were also required to be euthyroid or have mild hypo- or hyperthyroidism. Diabetes, if present, was well controlled with HbA1C < 9.0%. Participants had moderate-to-severe disease as shown by clinical parameters including the degree of proptosis (see table below). Degree of Proptosis: Upper limit of Normal for Race/Sex African American White Asian Female 23 mm 19 mm 16 mm (Thai) 16 mm (Chinese) Male 24 mm 21 mm 17 mm (Thai) 18.6 mm (Chinese) Clinical Activity Score Item 1 2 3 4 Description Spontaneous orbital pain Gaze evoked orbital pain Eyelid swelling that is considered to be due to active (inflammatory phase) TED/GO Eyelid erythema 1 5 6 7 Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO Chemosis (swelling of the conjunctiva) Inflammation of caruncle (red prominence at the inner corner of the eye) or plica (crescent fold in the medial conjunctive lying lateral to the caruncle) Scoring: Each item is scored (1= present; 0= absent) and scores for each are summed for total score TED= Thyroid Eye Disease; GO= Graves’ Orbitopathy Tepezza has primarily been studied as a one-course therapeutic option. Recently, the OpticX trial (an open label extension of the OPTIC trial) evaluated Tepezza in individuals unresponsive or who experienced a disease flare after treatment with Tepezza (n=14) or placebo (n=37) (Douglas 2022). Both Tepezza nonresponders (n=5) and responders who experienced a disease flare (n=8) were retreated with a second course. Of nonresponders, 2 subsequently responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatments early. In relapsed individuals, 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). Tepezza’s duration of response and the efficacy of subsequent courses are still not fully understood as OpticX provided limited data regarding the retreatment of Tepezza. Tepezza has a warning for exacerbation of preexisting inflammatory bowel disease. Individuals should be monitored for IBD flare and should be considered for discontinuation if this occurs. Tepezza also has a warning for hyperglycemia as 10% of patients experienced this adverse effect in clinical trials. Hyperglycemia events should be closely monitored and controlled. Individuals with pre-existing diabetes should be well controlled prior to starting Tepezza. Clinical Criteria When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose. Tepezza (teprotumumab-trbw) Requests for one course* of Tepezza (teprotumumab-trbw) may be approved if the following criteria are met (Douglas 2020): I. II. Individual has a diagnosis of Thyroid Eye Disease; AND Documentation is provided that individual has symptomatic moderate to severe disease, as defined by one or more of the following: A. Lid retraction ≥ 2 mm; OR B. Moderate or severe soft tissue involvement; OR C. Proptosis ≥ 3 mm above normal for race and gender; OR D. Intermittent or constant diplopia; AND III. IV. Documentation is provided that individual has a clinical activity score (CAS) greater than or equal to 4 in the more severely affected eye; AND Documentation is provided that one of the following applies: A. Thyroid function tests are provided and are within normal limits as defined by laboratory standard (i.e. individual is euthyroid); OR B. Thyroid function tests show free thyroxine (T4) and free triiodothyronine (T3) levels less than 50% above or below normal limits as defined by laboratory standard. Tepezza (teprotumumab-trbw) may not be approved for the following: I. II. III. More than one course* of treatment; OR Individual has had prior orbital irradiation or eye surgery for TED; OR Individual has decreased best-corrected visual acuity due to optic neuropathy as defined by decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect; OR IV. Individual has unresponsive corneal decompensation; OR V. When the above criteria are not met and for all other indications. *Approval Duration: One course of treatment; defined as a total of 8 intravenous infusions of Tepezza (teprotumumab) administered every 3 weeks Quantity Limits Tepezza (teprotumumab-trbw) Quantity Limits Tepezza (teprotumumab-trbw) 500 mg vial Drug Initial dose: One 10 mg/kg infusion Subsequent doses: 20mg/kg every 3 weeks for seven infusions Limit 2 Coding The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. HCPCS J3241 ICD-10 Diagnosis E05.00 Injection, teprotumumab-trbw, 10 mg (Effective 10/1/2020) Thyrotoxicosis with diffuse goiter without thyrotoxic crisis or storm Document History Reviewed: 05/19/2023