Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Nueromyelitis Optica Spectrum Disorder (NMOSD).

Treatment: Gammaglobulin liquid (IVIG) infusion.

The insurer denied Gammaglobulin liquid (IVIG) infusion.

The denial was upheld.

This is a male patient who was seen by a provider for a follow-up after a recent hospitalization for Nueromyelitis Optica Spectrum Disorder (NMOSD).  The patient was hospitalized due to worsening neurologic disease and a delay in treatment with IVIG, rituximab and IV steroids. The patient did receive 2 g/kilograms of IVIG and 1000 mg of rituximab while in the hospital.  He had a magnetic resonance imaging (MRI) of the brain and cervical spine revealing persistent abnormal contrast-enhancing lesions throughout the brainstem, cerebellum and upper cervical spinal cord with multiple T2 hyperintense lesions in the thoracic spinal cord.  The patient did tolerate medication with some improvement.  The patient was scheduled for his second rituximab infusion 2 weeks after discharge.  It was reported that the patient requires a walker to ambulate. He has an abnormal speech, severe dizziness, disequilibrium and near syncopal episodes. On physical examination it was reported the patient had weakness in both upper and lower extremities and 3+ reflexes throughout with the exception of ankle which were 4+.  There was absent Babinski reflex on the right and left. There was decreased sensation in the patient had a wide-based gait that was also ataxic.  The physician reported that the patient had very little improvement thus far, IVIG was to continue in combination with rituximab; extensive physical therapy was also recommended.  The patient did return to his next appointment where it was noted that the patient most likely had severe neuromyelitis optica spectrum disorder. The physician reported that the patient had received plasma exchange and  IV steroids with minimal improvement; IVIG, IV steroids and rituximab were recommended.

Intravenous immune globulin has not been specifically evaluated for acute attacks of NMOSD and is rarely used in this setting. Additionally, data are lacking to show that this medication is a preferred agent for attack prevention compared to other therapies. The evidence of efficacy for systemic immunotherapy comes mainly from observational studies of agents including azathioprine, mycophenolate mofetil, rituximab, methotrexate, mitoxantrone, and oral glucocorticoids. The efficacy of newer medications such as eculizumab and toclizumab has also been described

IVIG is not FDA approved or manufacturer supported for treatment of NMOSD. 

As noted above, evidence is lacking for the use of IVIG as a strategy for treatment of acute attacks or for prevention of attacks. Treatments with the best evidence for preventing attacks include azathioprine, mycophenolate mofetil, rituximab, methotrexate, mitoxantrone, and oral glucocorticoids.  If the physician has determined that the member has disease that is refractory to these therapies, agent such as toclizumab and eculizumab could be used. 

IVIG is not likely to be more beneficial than other standard treatment options. These include eculizumab, toclizumab, because the natural history of NMOSD is one of stepwise deterioration due recurrent attacks and accumulated disability, long-term immunotherapy is indicated to reduce the risk of relapse as soon as the diagnosis of NMOSD is made. In seropositive patients, eculizumab was highly effective for reducing the relapse rate compared with placebo in a randomized trial. For patients who meet diagnostic criteria for NMOSD without AQP4-IgG or who meet criteria with unknown AQP4-IgG status, alternative agents include rituximab, azathioprine, or mycophenolate.

The carrier's denial of Gammaglobulin liquid (IVIG) infusion should be upheld.