CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Inebilizumab-cdon (Uplizna) — Coverage Criteria for IgG4‑RD, NMOSD (AQP4+), and gMG (antibody‑positive)

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Defines prior authorization, documentation, and medical necessity criteria for inebilizumab-cdon (Uplizna) for FDA-approved indications (IgG4‑RD, AQP4 antibody‑positive NMOSD, and antibody‑positive generalized myasthenia gravis) for BlueCross BlueShield of Tennessee members.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyInebilizumab-cdon (Uplizna) — Coverage Criteria for IgG4‑RD, NMOSD, and gMG

Policy CodePolicy N/A

Change TypeRoutine review — no material changes

Effective DateJun 30, 2025

Last ReviewJun 30, 2026

Next Review DateN/A

Key ActionObtain prior authorization and submit required documentation (e.g., antibody test results or chart notes) to support coverage.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 moauthorization period

3FDA indications

≥5MG‑ADL threshold

AQP4+Required biomarker (NMOSD)

Coverage and Medical Necessity Criteria

Neuromyelitis Optica Spectrum Disorder (NMOSD) - Initial Therapy

Authorization of 12 months may be granted when ALL of the following are met:

NMOSD initial requirements: Member exhibits one of the following core clinical characteristics of NMOSD and is anti‑aquaporin‑4 (AQP4) antibody positive: 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 MRI lesions; or 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.

12‑month authorization possible.

Immunoglobulin G4‑related Disease (IgG4‑RD) - Initial Therapy

Authorization of 12 months may be granted when ALL of the following are met:

IgG4‑RD initial requirements: Member has a clinical diagnosis of IgG4‑related disease confirmed by either clinical or radiologic involvement of a characteristic organ or pathologic evidence from a characteristic organ; member is experiencing an IgG4‑RD flare requiring initiation or continuation of glucocorticoid treatment within the past 4 weeks; alternative causes of the member's clinical signs and symptoms have been evaluated and ruled out; and member has a history of IgG4‑RD affecting at least one organ/site at any time in the course of disease.

See Appendices A and B for diagnostic features and common mimickers; 12‑month authorization possible.

Generalized Myasthenia Gravis (gMG) - Initial Therapy

Authorization of 12 months may be granted when ALL of the following are met:

gMG initial requirements: Myasthenia Gravis Foundation of America (MGFA) clinical classification II–IV; positive anti‑acetylcholine receptor (AChR) or anti‑MuSK antibody; MG‑ADL total score greater than or equal to 5; and meets one of the following: inadequate response or intolerable adverse event to at least two immunosuppressive therapies over at least 12 months; OR inadequate response/intolerable adverse event to at least one immunosuppressive therapy plus IVIG over at least 12 months; OR documented clinical reason to avoid immunosuppressive agents and IVIG. The requested medication will not be used in combination with a neonatal Fc receptor blocker or complement inhibitor for the treatment of gMG.MG‑ADL >=5

12‑month authorization possible.

Reauthorization / Continued Treatment

Authorization of 12 months may be granted for continued treatment when ALL of the following are met (by indication):

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

12‑month renewal.

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

12‑month renewal.

gMG reauthorization: The member demonstrates a positive response to therapy (e.g., improvement in MG‑ADL, MG Manual Muscle Test (MMT), or MG Composite); there is no evidence of unacceptable toxicity or disease progression while on the current regimen; and the requested medication will not be used in combination with a neonatal Fc receptor blocker or complement inhibitor for the treatment of gMG.

12‑month renewal.

All indications other than the FDA‑approved indications listed for Uplizna are considered experimental/investigational and not medically necessary. The FDA‑approved indications are limited to: Immunoglobulin G4‑related disease (IgG4‑RD) in adults; neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti‑aquaporin‑4 (AQP4) antibody positive; and generalized myasthenia gravis (gMG) in adults who are anti‑AChR or anti‑MuSK antibody positive. Requests for use outside these indications will be denied as not medically necessary.

Use of Uplizna for indications that are not FDA‑approved and are not supported by recognized compendia or peer‑reviewed literature is considered not medically necessary. Prior authorization for non‑FDA uses will not be approved absent strong, guideline‑supported evidence, since such uses are treated as experimental/investigational under this policy.

Key Coding and Scoring Thresholds

MG‑ADL score — Minimum for gMG coverage

Minimum MG-ADL scoreMG-ADL total score >= 5

Supporting classificationMGFA clinical classification II–IV required

Antibody requirementPositive anti-AChR or anti-MuSK antibody

Prior therapy requirementDocumented prior therapy trial per gMG criteria (see policy) may be required for coverage

AQP4 antibody positive NMOSD — Diagnostic biomarker & core clinical characteristic

Required biomarkerPositive anti-aquaporin-4 (AQP4) antibody

Core clinical characteristicAt least one NMOSD core clinical characteristic (e.g., optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy/diencephalic syndrome with NMOSD-typical MRI lesions, or symptomatic cerebral syndrome with NMOSD-typical brain lesions)

Concomitant biologicsRequested medication must not be given concomitantly with other biologics for NMOSD

IgG4‑related disease (IgG4‑RD) — Diagnostic criteria summary

Clinical/radiologic or pathologic confirmationClinical or radiologic involvement of a characteristic organ OR pathologic evidence from a characteristic organ

Recent glucocorticoid-responsive flareMember is experiencing an IgG4-RD flare requiring initiation or continuation of glucocorticoid treatment within the past 4 weeks

Alternative causes ruled outAlternative causes of signs/symptoms have been evaluated and excluded (see Appendix B for mimickers)

History of organ involvementMember has history of IgG4-RD affecting ≥1 organ/site at any time

Generalized myasthenia gravis (gMG) — Diagnostic & prior therapy requirements

Antibody positivityPositive anti-AChR or anti-MuSK antibody required

Clinical severityMGFA clinical classification II–IV

MG-ADL thresholdMG-ADL total score >= 5

Prior therapy trialsInadequate response or intolerable adverse event to ≥2 immunosuppressive therapies over ≥12 months, OR inadequate response/intolerable adverse event to ≥1 immunosuppressive therapy plus IVIG over ≥12 months, OR documented reason to avoid immunosuppressive agents and IVIG

Concomitant therapy restrictionNot to be used in combination with an FcRn blocker (e.g., Rystiggo, Vyvgart) or complement inhibitor (e.g., Soliris) for gMG

Prior Authorization, Documentation, and Denial Triggers

Prior Authorization

Prior authorization required (up to 12 months)

Prior authorization is required for inebilizumab (Uplizna); when all indication‑specific criteria are met, authorization of up to 12 months may be granted.

Step Therapy

Step therapy required per plan document

Treatment requires adherence to the health plan's step therapy policy for provider‑administered specialty medications; follow the 'Step Therapy Requirements for Provider Administered Specialty Medications' document linked by the plan.

Documentation Required

Required documentation to initiate prior authorization

Include indication‑specific supporting documentation with the prior authorization request: for NMOSD initial requests submit the immunoassay used to confirm anti‑AQP4 antibody; for IgG4‑RD initial requests submit chart notes/medical records documenting clinical diagnosis, a glucocorticoid‑requiring flare within the past 4 weeks, and organ involvement; for gMG initial requests submit positive AChR or MuSK antibody test, MGFA classification, MG‑ADL score, and prior medication history/response. For continuation requests, submit chart notes documenting positive clinical response.

NMOSD initial: immunoassay confirming anti‑AQP4 antibody (per documentation list).
IgG4‑RD initial: chart notes showing clinical diagnosis, flare requiring glucocorticoid within 4 weeks, and involvement of ≥1 organ/site.
gMG initial: positive AChR or MuSK antibody test, MGFA class II–IV, MG‑ADL score (≥5), and prior therapies with responses.
Continuation (all indications): chart notes or medical record documentation supporting positive clinical response.

Denial Risk

Triggers for denial (non‑covered uses and unmet criteria)

Requests for uses outside the listed FDA‑approved indications are considered experimental/investigational and not medically necessary and may be denied; lack of required antibody positivity or failure to meet the indication‑specific clinical criteria can also trigger denial.

Non–FDA‑approved indications are considered experimental/investigational and not medically necessary.
NMOSD: denial trigger if member is not anti‑AQP4 antibody positive or lacks required core clinical characteristics.
gMG: denial trigger if member is not AChR or MuSK antibody positive, or does not meet MGFA class II–IV and MG‑ADL ≥5.

Drug Background and Indications

Inebilizumab‑cdon (Uplizna) is a monoclonal antibody with FDA approvals limited to three adult indications: Immunoglobulin G4‑related disease (IgG4‑RD), neuromyelitis optica spectrum disorder (NMOSD) in patients who are AQP4 antibody positive, and generalized myasthenia gravis (gMG) in patients who are positive for anti‑AChR or anti‑MuSK antibodies. Coverage under this policy is restricted to those FDA‑approved uses; therapies outside those indications are considered experimental/investigational and not medically necessary.

Definitions and Diagnostic Criteria

AQP4 antibody positive NMOSD definition

AQP4 antibody requirementPositive anti-aquaporin-4 (AQP4) antibody required for NMOSD coverage

At least one core characteristicPresence of ≥1 NMOSD core clinical characteristic (e.g., optic neuritis, acute myelitis, area postrema syndrome, etc.)

No concomitant biologicsMedication cannot be given with other biologics for NMOSD

IgG4‑related disease (IgG4‑RD) definition

Organ involvement or pathologyClinical or radiologic involvement of a characteristic organ OR pathologic evidence from a characteristic organ

Pathologic criteria detailsPathologic diagnosis requires two of: dense lymphocyte and plasma cell infiltration with fibrosis; IgG4+/IgG+ plasma cell ratio >40% and >10 IgG4+ plasma cells/HPF; typical tissue fibrosis (storiform) or obliterative phlebitis

Characteristic organsCharacteristic organs include pancreas, salivary glands, bile ducts, orbits, kidney, lung, aorta, retroperitoneum, pachymeninges, thyroid (Riedel's)

Generalized myasthenia gravis (gMG) definition

MGFA classMGFA clinical classification II–IV

Antibody statusPositive anti-AChR or anti-MuSK antibody

MG-ADL thresholdMG-ADL total score >= 5

Prior immunosuppressive therapyInadequate response or intolerable adverse event to ≥2 immunosuppressive therapies over ≥12 months OR specified alternatives (see policy)

Policy Revision History

2026-06-30policy_reviewLatest

Medical Policy Manual approved; document marked 'Do Not Implement until 6/30/26' and references updated (includes clinical references and package insert).

2025-12-01reference_update

Package insert for Uplizna (Inebilizumab-cdon) dated December 2025 added to references.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyInebilizumab-cdon (Uplizna) — Coverage Criteria for IgG4‑RD, NMOSD, and gMG

Policy CodePolicy N/A

Change TypeRoutine review — no material changes

Effective DateJun 30, 2025

Last ReviewJun 30, 2026

Next Review DateN/A

Key ActionObtain prior authorization and submit required documentation (e.g., antibody test results or chart notes) to support coverage.

SourceLink

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