Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Small fiber neuropathy
Treatment: Gammagard (J1569)
The insurer denied: Gammagard (J1569)
The denial is upheld.

This patient is an adult male with history of small fiber polyneuropathy. The patient has a prior skin biopsy that showed small fiber neuropathy. The patient has responded some to prednisone; however, he is unable to taper prednisone. The request for intravenous immunoglobulin (IVIG) was initially denied due to the patient not having a United States Food 
and Drug Administration (FDA) approved indication. The reason why the provider is appealing the determination is because clinical studies do show improvement in small fiber neuropathy when treated with intravenous immunoglobulin.

The health plan should not cover the proposed treatment.

 The requested health service or treatment is not more beneficial than any standard treatment for the patient's condition or disease. This patient has small fiber neuropathy based on skin biopsy without a known underlying autoimmune cause. The role of antibodies in development of neuropathy has not been proven. There are many diagnostic tests that can be used in the workup of peripheral neuropathy. Electrodiagnostic studies are normal unless there is a coexistent large fiber neuropathy. A diagnosis of small fiber neuropathy is confirmed by quantitative sensory testing or punch skin biopsies demonstrating reduction in intraepidermal nerve fiber density. The distribution of abnormal nerve fiber density in skin biopsies obtained in proximal and distal sites of the same limb can help differentiate length versus non-length dependent neuropathies. Other diagnostic tests include quantitative sensory testing for thermal sensations, laser evoked potentials, sympathetic skin response, and electrochemical skin conductance. Treatment of small-fiber neuropathy is aimed initially at symptomatic relief of the associated pain. First-line therapeutic agents include gabapentin and pregabalin. Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine or venlafaxine may be substituted or added to first-line therapy if pain control is inadequate. Tricyclic antidepressants (TCA) may also be effective for treatment of neuropathic pain. A trial of immunomodulatory or immunosuppressive therapy is appropriate in patients in whom sensory deficits are rapidly progressive or severe or in those who have failed symptomatic therapy. Intravenous immunoglobulin (IVIG), in a dose of 0.4 grams per kilogram (g/kg) for five days, is generally recommended, based on beneficial results in anecdotal case reports and several small series, although duration of therapy is not clear. Small fiber neuropathies may not respond to corticosteroid therapy; however, this observation is limited by the coexistence of multiple forms of peripheral neuropathy in the 
studied populations. Small studies evaluating rituximab in painful sensory neuropathy have had disappointing results. While there are studies where intravenous immunoglobulin has been utilized in those who have progressive peripheral neuropathy associated to their Sjogren's or underlying autoimmune disorders, the clinical documentation of this patient does not support that the patient has Sjogren's or that the patient has a known underlying autoimmune condition. It also does not show that the patient has previously tried and failed any standard therapies. Therefore, the requested health service or treatment is not more beneficial than any standard treatment for the patient's condition or disease.