This policy version was replaced on August 2, 2021. To find the newest version, go to https://www.bluecrossmn.com/providers/medical-policy-and-utilization-management, read and accept the Blue Cross Medical Policy Statement, then select “Blue Cross and Blue Shield of Minnesota Medical Policies.” This will bring up the Medical Policy search screen. Enter the policy number without the version number (last 3 digits).

Inebilizumab is a recombinant, humanized monoclonal antibody that binds to the CD19 surface antigen of B cells, thereby depleting a wide range of B cell lymphocytes. It is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD). Neuromyelitis optica spectrum disorder (NMOSD) is a rare, relapsing, autoimmune, potentially fatal disease inflammatory disease of the central nervous system that causes blindness and paralysis.  Inebilizumab is administered by intravenous infusion. 

The U.S. Food and Drug Administration (FDA) has approved inebilizumab (Uplizna™) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.

Serious adverse reactions have occurred in patients receiving inebilizumab, including infusion reactions, opportunistic infections (including progressive multifocal leukoencephalopathy), and reduction in immunoglobulins.  Due to the prevalence of infusion reactions, which may be severe, premedication with corticosteroids, antihistamines, and antipyretics are recommended prior to each infusion.

I.     Initial Review for Inebilizumab (Uplizna™)

Inebilizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Age 18 years or older; AND
• Diagnosis of neuromyelitis optica spectrum disorder (NMOSD); AND
• Positive serological test for aquaporin-4 (AQP4) antibodies; AND
• Clinical characteristics of NMOSD (e.g., optic neuritis, acute myelitis); AND
• ONE of the following:
  • History of a relapse that required rescue therapy (intravenous corticosteroid, intravenous immunoglobulin, and/or plasma exchange) during the previous 12 months prior to initiating inebilizumab; or
  • History of at least 2 relapses that required rescue therapy during the previous 24 months;
• AND
• Expanded Disability Status Scale (EDSS) score ≤8.0; AND
• ONE of the following: 
  • Previously tried and failed satralizumab (Enspryng™); OR 
  • Documented intolerance, FDA labeled contraindication, or hypersensitivity to satralizumab (Enspryng™); 
• AND
• Not used in combination with other biologic immunomodulators (e.g., rituximab, eculizumab); AND
• No evidence of active infections; AND
• For patients not currently receiving inebilizumab, ALL of the following:
  • Has been screened for hepatitis B infection and has begun therapy if appropriate; and
  • Has been screened for tuberculosis and has begun therapy if appropriate; and
  • Has completed quantitative serum immunoglobulin testing which demonstrates sufficient levels that do not indicate immune compromise; and
  • No immunizations with live or live-attenuated vaccines within 4 weeks prior to initiation of treatment;
• AND
• Prescribed by or in consultation with a specialist (e.g., neurologist); AND
• No FDA labeled contraindications to inebilizumab (see table 1 below); AND
• The dose is within the FDA labeled dose (see table 2 below); AND
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).
  

II.    Renewal Review for Inebilizumab (Uplizna™)

Inebilizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for inebilizumab through the initial review process; AND
• Demonstrated positive clinical response to inebilizumab therapy (e.g., reduced rates of relapses, improvement or stabilization of paralysis, stabilization and/or slowing of disease progression); AND
• Not used in combination with other biologic immunomodulators (e.g. rituximab, eculizumab); AND
• No evidence of active infections; AND
• Prescribed by or in consultation with a specialist (e.g., neurologist); AND
• No FDA labeled contraindications to inebilizumab (see table 1 below); AND
• The dose is within the FDA labeled dose (see table 2 below).

III.  Experimental/Investigative Uses

All other uses of inebilizumab are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

Table 1.  FDA Labeled Contraindications

Table 2. Dosing

NOTE:  See documentation submission requirements below if the requested dose is higher or more frequent than the dosing criteria provided in this table. 

Documentation Submission:

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization. In addition, the following documentation must also be submitted:

Initial Review

1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
2. Clinical notes describing concomitant medications and pre-dose screening assessments.
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
4. For commercial health plan members only, when step therapy requirements apply for the requested indication, documentation for one or more of the step therapy supplement criteria MUST be provided (see policy II-242).
   

Renewal Review

1. Documentation of prior approval for inebilizumab through the initial review process.
2. Documentation supporting positive clinical response (e.g., slowing of disease progression or decrease in symptom severity and/or frequency).
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.