Requires Step Therapy See “Step Therapy Requirements for Provider Administered Specialty Medications” Document at: https://www.bcbst.com/docs/providers/Comm_BC_PAD_Step_Therapy_Guide.pdf

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan or government

POLICY

INDICATIONS

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications

Uplizna is indicated for the treatment of:

Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
Immunoglobulin G4-related disease (IgG4-RD) in adult patients.
Generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle specific tyrosine kinase (MuSK) antibody positive.

All other indications are considered experimental/investigational and not medically necessary.

DOCUMENTATION

Submission of the following information is necessary to initiate the prior authorization review:

Neuromyelitis optica spectrum disorder (NMOSD)

For initial requests: Immunoassay used to confirm anti-aquaporin-4 (AQP4) antibody is present.
For continuation requests: Chart notes or medical record documentation supporting positive clinical response.

Immunoglobulin G4-related disease (IgG4-RD)

For initial requests, chart notes or medical records documenting:

Member has a clinical diagnosis of IgG4-RD.
Member is experiencing an IgG4-RD flare requiring glucocorticoid treatment (within the past 4 weeks).
IgG4-RD is affecting at least 1 organ/site.

For continuation requests: Chart notes or medical record documentation supporting positive clinical response.

Generalized myasthenia gravis (gMG)

For initial requests, chart notes, medical records, or claims history documenting:

Positive anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody test.
Myasthenia Gravis Foundation of America (MGFA) clinical classification.
MG activities of daily living score.
Previous medications tried, including response to therapy. If therapy is not advisable, documentation of clinical reasons to avoid therapy.

For continuation requests: Chart notes or medical record documentation supporting positive clinical response.

COVERAGE CRITERIA

Neuromyelitis Optica Spectrum Disorder (NMOSD)

Authorization of 12 months may be granted for treatment of neuromyelitis optica spectrum disorder (NMOSD) when all of the following criteria are met:

Anti-aquaporin-4 (AQP4) antibody positive
Member exhibits one of the following core clinical characteristics of NMOSD:

Optic neuritis
Acute myelitis
Area postrema syndrome (episode of otherwise unexplained hiccups or nausea and vomiting)
Acute brainstem syndrome
Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic magnetic resonance imaging (MRI) lesions
Symptomatic cerebral syndrome with NMOSD-typical brain lesions

The member will not receive the requested medication concomitantly with other biologics for the treatment of NMOSD.

Immunoglobulin G4-related Disease (IgG4-RD)

Authorization of 12 months may be granted for treatment of immunoglobulin G4-related disease (IgG4-RD) when all of the following criteria are met:

Member has a clinical diagnosis of IgG4-RD confirmed by either of the following (please see Appendix A for evaluations and characteristic organs to confirm diagnosis):

Clinical or radiologic involvement of a characteristic organ.
Pathologic evidence from a characteristic organ.

Alternative causes of member’s clinical signs and symptoms have been evaluated and ruled out (please see Appendix B for common mimickers of IgG4-RD).
Member is experiencing an IgG4-RD flare that requires initiation or continuation of glucocorticoid treatment (within the past 4 weeks).
Member has a history of IgG4-RD affecting at least 1 organ/site at any time in the course of IgG4-RD.

Generalized Myasthenia Gravis (gMG)

Authorization of 12 months may be granted for treatment of generalized myasthenia gravis (gMG) when all of the following criteria are met:

Anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.
Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV.
MG activities of daily living (MG-ADL) total score of greater than or equal to 5.
Meets one of the following:

Member has had an inadequate response or intolerable adverse event to at least two immunosuppressive therapies over the course of at least 12 months (e.g., azathioprine, corticosteroids, cyclosporine, methotrexate, mycophenolate, tacrolimus).
Member has had an inadequate response or intolerable adverse event to at least one immunosuppressive therapy and intravenous immunoglobulin (IVIG) over the course of at least 12 months.
Member has a documented clinical reason to avoid therapy with immunosuppressive agents and IVIG.

The requested medication will not be used in combination with a neonatal Fc receptor blocker (e.g., Rystiggo, Vyvgart, Vyvgart Hytrulo) or complement inhibitor (e.g., Soliris, Ultomiris, Zilbrysq) for the treatment of gMG.

CONTINUATION OF THERAPY

Neuromyelitis Optica Spectrum Disorder (NMOSD)

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when all of the following criteria are met:

There is no evidence of unacceptable toxicity or disease progression while on the current regimen.
The member demonstrates a positive response to therapy (e.g., reduction in number of relapses).
The member will not receive the requested medication concomitantly with other biologics for the treatment of NMOSD.

Immunoglobulin G4-related Disease (IgG4-RD)

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when all of the following criteria are met:

There is no evidence of unacceptable toxicity or disease progression while on the current regimen.
The member demonstrates a positive response to therapy (e.g., reduction in IgG4-RD flares).

Generalized Myasthenia Gravis (gMG)

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when all of the following criteria are met:

There is no evidence of unacceptable toxicity or disease progression while on the current regimen.
The member demonstrates a positive response to therapy (e.g., improvement in MG-ADL score, MG Manual Muscle Test (MMT), MG Composite).
The requested medication will not be used in combination with a neonatal Fc receptor blocker (e.g., Rystiggo, Vyvgart, Vyvgart Hytrulo) or complement inhibitor (e.g., Soliris, Ultomiris, Zilbrysq) for the treatment of gMG.

Appendices

Appendix A: Adapted from the 2020 Revised Comprehensive Diagnostic Criteria for IgG4-RD and the 2019 ACR/EULAR Classification Criteria for IgG4-RD

Clinical or radiological features:

One or more organs show diffuse or localized swelling or a mass or nodule characteristic of IgG4-RD. In single organ involvement, lymph node swelling is omitted.
Note: Nearly any organ can be affected, but characteristic organs involved include:
- Pancreas
- Salivary gland
- Bile ducts
- Orbits
- Kidney
- Lung
- Aorta
- Retroperitoneum
- Pachymeninges
- Thyroid gland (Riedel’s thyroiditis)

Pathological diagnosis (positivity for two of the following three criteria):

Dense lymphocyte and plasma cell infiltration with fibrosis.
Ratio of IgG4-positive plasma cells /IgG-positive cells greater than 40% and the number of IgG4-positive plasma cells greater than 10 per high powered field.
Typical tissue fibrosis, particularly storiform fibrosis, or obliterative phlebitis.

Appendix B: Common Mimickers of IgG4-RD

Malignancy
Vasculitis
Sjogren’s syndrome
Primary granulomatous inflammation (including sarcoidosis)
Infection
Multicentric Castleman’s disease
Erdheim-Chester disease
Crohn's disease or ulcerative colitis (if only pancreatobiliary disease is present)
Hashimoto thyroiditis (if only the thyroid is affected)

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

ADDITIONAL INFORMATION

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

REFERENCES

Uplizna [package insert].Deerfield, IL: Horizon Therapeutics USA, Inc.; December 2025.
Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015; 85:177-189.

Stone JH, Khosroshahi A, Zhang W, et al. Inebilizumab for Treatment of IgG4-Related Disease. N Engl J Med. 2025 Mar 27;392(12):1168-1177.
Wallace, Z.S., Naden, R.P., Chari, S., Choi, H., et al. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease. Arthritis Rheumatol, 72: 7-19.
Umehara H, Okazaki K, Kawa S, et al. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Mod Rheumatol. 2021;31(3):529-533.
Sanders D, Wolfe G, Benatar M et al. International consensus guidance for management of myasthenia gravis. Neurology. 2021; 96 (3) 114-122.
Barnett C, Herbelin L, Dimachkie MM, Barohn RJ. Measuring Clinical Treatment Response in Myasthenia Gravis. Neurol Clin. 2018 May;36(2):339-353.

ORIGINAL EFFECTIVE DATE: 9/1/2020

MOST RECENT REVIEW DATE: 6/30/2026

ID_CHS_2025b

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information.