Background

Uplizna (inebilizumab-cdon) is a CD19-directed cytolytic antibody for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult individuals who are anti-aquaporin-4 (AQP4) antibody positive. It is a genetically humanized monoclonal antibody that binds to CD19, a cell surface antigen that is present on pre-B and mature B cell lymphocytes.  NMOSD is an autoimmune disorder, (previously known as Devic disease), of the central nervous system that predominantly affects the optic nerves and spinal cord.  Estimates of prevalence and incidence vary, but it ranges from 0.5 to 10 per 100,000.  The incidence of NMOSD is up to 10 times higher in women than men and is more prevalent in Asians and Africans.  Signs and symptoms include myelitis, ocular pain, temporary vision loss and weakness is the arms and legs.

Policy (Criteria)

Coverage of these drugs is provided when the criteria below is met and for non-preferred products there has been a trial and failure of preferred therapy (if applicable).

Inebilizumab may be considered MEDICALLY NECESSARY for the following condition(s):

Neuromyelitis Optica Spectrum Disorder (NMOSD)

1. Diagnosis of neuromyelitis optica spectrum disorder (NMOSD)
2. Member is anti-aquaporin-4 (AQP4) antibody positive
3. Prescribed by or in consultation with one of the following:

• Neurologist
• Ophthalmologist

Immunoglobulin G4-Related Disease (IgG4-RD)

1. Diagnosis of Immunoglobulin G4-Related Disease (IgG4-RD)
2. Presence of disease involving two or more organ systems or sites (e.g., Pancreas,
3. One of the following:

• Member is currently being treated with a glucocorticoid (e.g., prednisone, methylprednisolone)
• Trial and failure, contraindication or intolerance to a glucocorticoid (e.g., prednisone, methylprednisolone)

Continuation therapy is considered MEDICALLY NECESSARY when the following criteria are met:

      1. Documentation of positive clinical response to therapy

Authorization duration: 12 months

References

1. Aktas O, Smith MA, Rees WA, Bennett JL, She D, Katz E, Cree BAC; N-MOmentum scientific group and the N-MOmentum study investigators.(2021) Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker. Ann Neurol. 2021 May;89(5):895-910. doi: 10.1002/ana.26067. Epub 2021 Mar 30. PMID: 33724534.
2. Chen Y, et al.(2022) Update on classification, diagnosis, and management of immunoglobulin G4-related disease. Chin Med J (Engl). 2022;135(4):381–392.
3. Cree BA C, Bennett JL, Kim HJ, et al.(2019) Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-Momentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 394:1352-63 Oct 12,2019. http://dx.doi.org/10.1016/S0140-6736(19)31817-3.
4. Cree BAC, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, She D, Rees W, Smith M, Cimbora D, Katz E, Bennett JL; N-MOmentum study investigators.(2024) Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial. Lancet Neurol. 2024 Jun;23(6):588-602. doi: 10.1016/S1474-4422(24)00077-2. PMID: 38760098.
5. Floreani A, et al.(2020) IgG4-related disease: changing epidemiology and new thoughts on a multisystem disease J Transl Autoimmun. 2020;4:100074.
6. Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M.(2014) Comparison of Relapse and Treatment Failure Rates Among Patients With Neuromyelitis Optica: Multicenter Study of Treatment Efficacy. JAMA Neurol. 2014;71(3):324–330. doi:10.1001/jamaneurol.2013.5699.
7. Moutsopoulous HM, et al.(2025) Treatment and prognosis of IgG4-related disease. In: Helfgott SM, Seo P, eds. UpToDate. Wolters Kluwer. Updated April 8, 2025. Accessed April 11, 2025
8. Nambiar S, et al.(2025) IgG4-related disease. In: StatPearls [Internet]. StatPearls Publishing; 2025. Updated August 8, 2023. Accessed April 11, 2025.
9. Stone JH, et al.(2025) Inebilizumab for treatment of IgG4-related disease. N Engl J Med. 2025;392(12):1168–1177.
10. Trebst C, Jarius S, Berthele A, et al.(2014) Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 2014; 261:1.
11. Uplizna (inebilizumab-cdon) for IgG4-Related Disease Rx Brief: Immunology, Published April 2025. Accessed July 21, 2025. Subscription required.
12. UPLIZNA (inebilizumab-cdon)(2024) package insert Gaithersburg,MD Viela Bio, INC 6/11/2020
13. Wallace ZS, et al.(2023) Incidence, prevalence and mortality of IgG4-related disease in the USA: a claims-based analysis of commercially insured adults. Ann Rheum Dis. 2023;82(7):957–962.
14. Wallace ZS, Naden RP, Chari S, et al.(2020) The 2019 American College of Rheumatology/European League against rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020;79(1):77-87.
15. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG; InternaPanel for NMO Diag(2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015 Jul 14;85(2):177-89. doi: 10.1212/WNL.0000000000001729. Epub 2015 Jun 19. PMID: 26092914; PMCID: PMC4515040.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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