Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Dermatomyositis
Treatment: J1561 - Gammaked 35g (grams) infused intravenously once daily for three days every four weeks for six months for 70 units per dose infusion for three for 210 units per infusion cycle for a total of 1,260 unit(s)
The insurer denied the J1561 - Gammaked 35g (grams) infused intravenously once daily for three days every four weeks for six months for 70 units per dose infusion for three for 210 units per infusion cycle for a total of 1,260 unit(s). 
The denial is overturned. 

The patient is a woman with dermatomyositis for whom Gammaked 35g infused intravenously is requested. Her biopsy results were consistent with a connective tissue disease, and she has failed treatment with corticosteroids.

Yes, the treatment with Gammaked is medically necessary.

Dermatomyositis (DM) and polymyositis (PM) are classified as idiopathic inflammatory myopathies. Defining the optimal treatment regimens for these disorders has been difficult because of the rarity of these disorders, their highly complex clinical phenotypes, and the limited number of randomized, double-blind clinical trials.
The following clinical features have been associated with a worse outcome:
-       Delay in the initiation of treatment for more than six months after symptom onset 
-       Greater weakness at presentation 
-      The presence of dysphagia 
-       Respiratory muscle weakness 
-       Interstitial lung disease 
-       Associated malignancy 
-       Cardiac involvement.

The patient has dysphagia (esophageal dysmotility), which puts her in a category with a worse prognosis. The goals of treatment are to improve muscle strength and to avoid the development of extra-muscular complications. In patients with dermatomyositis (DM), resolution of cutaneous disease manifestations is an additional goal. 

Despite the absence of placebo-controlled trials demonstrating their effectiveness, glucocorticoids are the cornerstone of initial therapy for dermatomyositis (DM) and polymyositis (PM). Some clinicians also begin treatment immediately with a glucocorticoid-sparing agent, generally azathioprine or methotrexate, particularly in patients who are severely ill. The patient has been on steroids for some time, with loss of response, and her dermatologist is choosing not to put her on conventional steroid-sparing agents, because they would result in immunosuppression and she lives in a COVID19 (Coronavirus Disease 2019) hot spot.

For dermatomyositis, immunoglobulin (IVIG [intravenous immunoglobulin]) is a reasonable second-line therapy for patients with refractory disease. The 2012 American Academy of Neurology guidelines support the use of IVIG for refractory DM (dermatomyositis), but found evidence insufficient to support or refute its use in PM (polymyositis). The expense of this treatment is an important consideration in its long-term use.

Two studies, one in DM (dermatomyositis) and one in PM (polymyositis), have provided evidence that IVIG is an effective short-term therapy for resistant myositis. The mechanism of action is not known.

The efficacy of IVIG (intravenous immunoglobulin) was illustrated in a double-blind, placebo-controlled trial of 15 patients with DM (dermatomyositis) who had resistant disease. The patients were continued on prednisone (mean dose 25 mg [milligrams]/day) and were then randomly assigned to a monthly infusion of either IVIG (intravenous immunoglobulin) (2 g [grams]/kg [kilograms]) or placebo for three months. Crossover to the other treatment arm was permitted for treatment failures.

The following findings were noted:
-      The eight patients assigned to IVIG (intravenous immunoglobulin) all had significant improvement in scores of muscle strength and neuromuscular symptoms; the seven patients assigned to placebo had no benefit.
-	Including patients crossed over to the other treatment arm, 12 patients received IVIG (intravenous immunoglobulin). Nine had major improvement in their symptoms, two had mild improvement, and one had no change.
-       Including patients crossed over to the other treatment arm, 11 patients received placebo. Three had mild improvement, three had no change, and five deteriorated.
-	Among responders, improvement became noticeable about 15 days after the first IVIG (intravenous immunoglobulin) infusion. Maximal improvement generally occurred between the second and third infusions. The time course of improvement in skin manifestations and serum muscle enzyme elevation mirrored improvement in clinical muscle strength.

An open study of IVIG (intravenous immunoglobulin) included 35 patients with PM (polymyositis), all of whom had disease that required ongoing glucocorticoid therapy. None could be weaned from glucocorticoids despite trials of one or more additional therapies, including methotrexate, azathioprine, cyclophosphamide, cyclosporine, chlorambucil, plasmapheresis, lymphapheresis, and total body irradiation.

Each patient was treated with IVIG (intravenous immunoglobulin) (1 g [gram]/kg [kilogram] per day for two days per month for four to six months). No changes had been made in the treatment regimen in the two months before IVIG (intravenous immunoglobulin), and existing therapies were not increased during IVIG (intravenous immunoglobulin).

The following findings were noted:
-	All 33 patients with initially elevated serum CK (creatine kinase) levels showed biochemical improvement, but not all patients with decreases in serum CK (creatine kinase) levels had improvements in muscle strength.
-	Improvement in muscle strength occurred in 25 of 35 patients and returned to near-normal in 10 of the 25 responders.
-	Among the 11 patients with esophageal dysfunction, dysphagia resolved completely during therapy in eight patients and improved significantly in another.
-	After the initial course of IVIG (intravenous immunoglobulin), 12 of the 25 responders had complete clinical responses (absence of myositis activity) while receiving not more than 6 mg [milligrams]/day of prednisone. The mean follow-up period for these patients was 39 months. Five patients discontinued all other medical treatments for myositis.
-	Six of the 25 IVIG (intravenous immunoglobulin) responders remained dependent on IVIG (intravenous immunoglobulin) infusions but did not require additional medication. After six infusions, the dose of IVIG (intravenous immunoglobulin) was reduced to 1 g/kg each month.
-	Seven of the 25 responders relapsed at an average time interval of 17 months after discontinuation of IVIG (intravenous immunoglobulin). Four of these patients responded to repeat IVIG (intravenous immunoglobulin) treatment; three were prescribed other therapies.

An alternative subcutaneous approach to the administration of IVIG (intravenous immunoglobulin) in patients with DM (dermatomyositis) and PM (polymyositis) has also been associated with clinical improvement in strength and quality of life measures. In this small case series of seven patients, the usual monthly dose was divided into weekly doses given subcutaneously through a programmable pump, and the treatment was evidenced to be safe and well-tolerated.

The patient has biopsy results that were consistent with a connective tissue disease (dermatomyositis), and she has failed treatment with corticosteroids. She is not a good candidate for conventional steroid sparing agents due to the risk of immunosuppression in the midst of a pandemic. Gammaked 35g (grams) infused intravenously once daily for three days every four weeks for six months for 70 units per dose infusion for three for 210 units per infusion cycle for a total of 1,260 unit(s) is medically appropriate and necessary.