ModifiedUnitedHealthcarePolicy 2026D0091J

Uplizna (inebilizumab-cdon) — Medical Benefit Drug Policy

Defines UnitedHealthcare medical necessity criteria, prior authorization and coverage considerations for Uplizna (inebilizumab-cdon) for NMOSD, IgG4-related disease, and generalized myasthenia gravis; applicable to providers prescribing/administering the drug under UnitedHealthcare commercial plans.

Policy Summary

PayerUnitedHealthcare

PolicyUplizna (inebilizumab-cdon) — Medical Benefit Drug Policy

Policy CodePolicy 2026D0091J

Change TypeCriteria additions and revisions (coverage groups, authorization rules, coding updates)

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with required medical records documenting diagnosis, antibody status, prior therapy history, MG-ADL/QMG scores and specialist consultation to support initial or reauthorization requests.

SourceLink

POLICY UPDATE CHANGES

Policy lists FDA-labeled dosing initiation and continuation criteria for NMOSD, IgG4-RD, and generalized myasthenia gravis with specific requirement for specialist prescribing/consultation and 12-month authorization limits.

Specifies treatment sequencing requirements (e.g., failure/intolerance to rituximab or anti-CD20) for NMOSD and IgG4-RD prior to Uplizna in some circumstances.

Defines clinical response criteria for continuation in gMG including 62 point improvement in MG-ADL and restrictions on concomitant therapies.

Revised coverage criteria for Neuromyelitis Optica Spectrum Disorder (NMOSD) removing prior relapse count requirements.

Added coverage language establishing Uplizna as proven and medically necessary for treatment of generalized myasthenia gravis (gMG) in patients who are anti-AChR or anti-MuSK antibody positive with specific initial and continuation criteria.

Added ICD-10 diagnosis codes G70.00 and G70.01 to applicable codes.

Updated Background, Clinical Evidence, FDA, and References sections to reflect current information.

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Coverage Criteria

Initial Therapy (NMOSD)

Covered when ALL of the following are met

NMOSD initial therapy: Diagnosis of neuromyelitis optica spectrum disorder (NMOSD) by a neurologist

Includes past medical history of 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

Serology: Positive serologic test for anti-aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies

Exclusion of MS: Diagnosis of multiple sclerosis or other diagnoses have been ruled out

Prior therapy requirement: Either history of failure of rituximab OR (history of intolerance/contraindication to rituximab AND physician attestation that same intolerance/severe adverse event would not be expected with Uplizna)

Medicare reviews may differ (see CMS section)

Dosing and prescriber: Uplizna is initiated according to the U.S. FDA labeled dosing for NMOSD and prescribed by or in consultation with a neurologist

Concomitant therapy restriction: Patient is not receiving Uplizna in combination with multiple sclerosis disease modifying therapies, complement inhibitors, or anti-IL6 therapy for the same indication

Continuation Therapy (NMOSD)

Covered when ALL of the following are met

Clinical response: Documentation of positive clinical response

Dosing: Uplizna is dosed according to the U.S. FDA labeled dosing for NMOSD

Concomitant therapy restriction: Patient is not receiving Uplizna in combination with multiple sclerosis DMTs, anti-IL6 therapy, complement inhibitors, or anti-CD20 therapy for the same indication

Authorization length: Reauthorization will be for no more than 12 months

Initial Therapy (IgG4-RD)

Covered when ALL of the following are met

Diagnosis of Immunoglobulin G4-related disease (IgG4-RD)

Classification criteria: Confirmation of IgG4-RD by positive assessment using the ACR/EULAR classification criteria, including involvement of ≥1 organ consistent with IgG4-RD, negative exclusion criteria, and positive inclusion criteria

Prior therapy requirement: History of failure, contraindication, or intolerance to glucocorticoids AND (history of failure of rituximab OR (intolerance/contraindication to rituximab AND physician attestation that same intolerance/severe adverse event would not be expected with Uplizna))

Medicare reviews may differ (see CMS section)

Dosing and prescriber: Uplizna is initiated according to the U.S. FDA labeled dosing for IgG4-RD and prescribed by or in consultation with a specialist with expertise in IgG4-RD

Continuation Therapy (IgG4-RD)

Covered when ALL of the following are met

Clinical response: Documentation of positive clinical response

Dosing and prescriber: Uplizna is dosed according to the U.S. FDA labeled dosing for IgG4-RD and prescribed by or in consultation with an IgG4-RD specialist

Concomitant therapy restriction: Patient is not receiving Uplizna in combination with a disease modifying therapy for IgG4-RD (e.g., rituximab)

Authorization length: Reauthorization will be for no more than 12 months

Initial Therapy (gMG)

Covered when ALL of the following are met

Diagnosis and serology: Diagnosis of generalized myasthenia gravis (gMG) with positive anti-AChR or anti-MuSK antibodies

Prior Uplizna exposure: Patient has not failed a previous course of Uplizna for gMG

Prior therapy requirements by serostatus: If anti-AChR positive: history of failure of ≥2 immunosuppressive agents over ≥12 months OR failure of ≥1 immunosuppressive therapy plus ≥4 courses of plasmapheresis/IVIG over ≥12 months; If anti-MuSK positive: history of failure of ≥1 immunosuppressive agent over ≥12 months

Step therapy applies only to anti-AChR subgroup.

Disease severity at initiation: MGFA Clinical Classification class II, III, or IV and MG-ADL total score ≥ 5 at initiation

Continuation Therapy (gMG)

Covered when ALL of the following are met

Prior Uplizna exposure: Patient has previously been treated with Uplizna

Clinical improvement: Medical records demonstrate improvement and/or maintenance of at least a 2 point improvement in MG-ADL score from pre-treatment baseline; reduction in signs and symptoms of myasthenia gravis; and maintenance, reduction, or discontinuation of baseline immunosuppressive therapy (add-on or escalation is considered treatment failure)MG-ADL improvement >=2 points

Add-on, dose escalation of baseline IST, or additional rescue therapy from baseline while on Uplizna is considered treatment failure.

Timing: Patient is not being given Uplizna sooner than 6 months from the start of the previous treatment cycle

Concomitant therapy restriction:

Initial Therapy — gMG (added language)

Uplizna is medically necessary for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-AChR antibody positive or anti-MuSK antibody positive when ALL of the following are met:

Initial Therapy criteria for gMG: Submission of medical records confirming: patient has not failed previous Uplizna; diagnosis of gMG; positive serologic test for anti-AChR or anti-MuSK antibodies; MGFA Clinical Classification class II, III, or IV at initiation; MG-ADL total score >= 5 at initiation; dosing per FDA label; prescribed by or in consultation with a neurologist; initial authorization <= 12 months.

Prior therapy requirement for anti-AChR positive patients: One of: history of failure of at least two immunosuppressive agents over at least 12 months OR history of failure of at least one immunosuppressive therapy plus 4 or more courses of plasmapheresis/plasma exchanges and/or immune globulin over at least 12 months without symptom control.

Step therapy applies only to anti-AChR subgroup.

Prior therapy requirement for anti-MuSK positive patients: History of failure of at least one immunosuppressive agent over at least 12 months.

Continuation of Therapy — gMG (added language)

Continuation of therapy (reauthorization) for gMG is medically necessary when ALL of the following are met:

Continuation general: Patient has previously been treated with Uplizna; documentation demonstrates improvement and/or maintenance of at least a 2-point improvement in the MG-ADL score from pre-treatment baseline; reduction in signs and symptoms of myasthenia gravis; maintenance, reduction, or discontinuation of baseline immunosuppressive therapy prior to starting Uplizna (add-on or escalation or additional rescue therapy from baseline is considered treatment failure); not receiving disallowed combination therapies; not being given Uplizna sooner than 6 months from start of previous treatment cycle; dosing per FDA label; prescribed by or in consultation with a neurologist; reauthorization for no more than 12 months.MG-ADL improvement >=2 points

Failure criteria include need for add-on/escalation of IST or additional rescue therapy while on Uplizna.

Use of Uplizna in combination with other therapies for the same indication is restricted. For NMOSD and IgG4-RD, the policy explicitly excludes concomitant use with disease-modifying therapies for those diseases (for example, multiple sclerosis DMTs in NMOSD or rituximab for IgG4-RD). For gMG, the policy prohibits concomitant administration of Uplizna with complement inhibitors, FcRn blockers, or intravenous or subcutaneous immune globulin when used to treat the same indication. These combination exclusions apply both at treatment initiation and during continuation/reauthorization assessments.

Operational notes: requests that indicate concurrent administration of Uplizna with any of the disallowed agents above should be considered noncompliant with the coverage criteria and may be denied. Documentation submitted for initial or continuation authorization must confirm the patient is not receiving Uplizna in combination with these excluded therapies.

The policy explicitly excludes combination use of Uplizna with a complement inhibitor (e.g., eculizumab, ravulizumab, zilucoplan), an FcRn blocker (e.g., nipocalimab, rozanolixizumab, efgartigimod alfa and formulations), or an immune globulin product for treatment of the same indication. Such combinations are considered disallowed and may render a request noncompliant with coverage criteria.

Continuation (reauthorization) for generalized myasthenia gravis requires documented clinical benefit. Medical records must demonstrate an improvement and/or maintenance of at least a 2-point improvement in the MG-ADL score from pre-treatment baseline, reduction in signs and symptoms of myasthenia gravis, and either maintenance, reduction, or discontinuation of baseline immunosuppressive therapy (IST) that was in place prior to starting Uplizna. If these response criteria are not met, continuation should be considered not medically necessary.

Additional continuation denial conditions include receiving Uplizna sooner than the required interval from a prior cycle (the policy requires retreatment no sooner than 6 months from the start of the previous treatment cycle) or documentation indicating concomitant use with excluded therapies (complement inhibitors, FcRn blockers, or immune globulin).

During the assessment period for clinical response, the policy considers escalation of baseline therapy or use of additional rescue therapy as indicators of treatment failure. Specifically, add-on therapy, dose escalation of baseline immunosuppressive therapy, or additional rescue therapy from baseline to treat myasthenia gravis or an exacerbation while on Uplizna will be regarded as treatment failure and therefore not meet continuation criteria.

Operationally, authorization reviewers should treat documentation of new or increased IST dosing or additional rescue interventions (for example, new courses of IVIG or plasmapheresis beyond those that justified initiation) after starting Uplizna as evidence against continued coverage.

Coding

Applicable HCPCS CodesHCPCS

J1823

Injection, inebilizumab-cdon, 1 mg.

Applicable Diagnosis CodesICD-10

D89.84	IgG4-related disease
G36.0	Neuromyelitis optica [Devic]
G70.00	Myasthenia gravis without (acute) exacerbation
G70.01	Myasthenia gravis with (acute) exacerbation

Applicable ICD-10 Diagnosis Codes (added)ICD-10

G70.00	Myasthenia gravis without (acute) exacerbation (added ICD-10 code per policy)
G70.01	Myasthenia gravis with (acute) exacerbation (added ICD-10 code per policy)

MG-ADL score — initiation threshold

Threshold>= 5 (MG-ADL total score at initiation)

ContextRequired for initial authorization of Uplizna for generalized myasthenia gravis (gMG)

Source detailPolicy specifies MG-ADL total score ≥ 5 at initiation of therapy

MG-ADL minimum at initiation

Minimum required at initiation>= 5 total MG-ADL score

Associated severityMust coincide with MGFA Clinical Classification II–IV at initiation

Provider Actions & Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Uplizna (inebilizumab-cdon). Initial and reauthorization approvals are limited to no more than 12 months. Submit complete clinical documentation to avoid delays or denial.

Initial and reauthorization approvals limited to <= 12 months
Prescribed by, or in consultation with, a neurologist (gMG/NMOSD) or specialist with expertise in IgG4-RD as applicable
Do not combine Uplizna with complement inhibitors, FcRn blockers, immune globulin, anti-CD20 therapy, or other disease-modifying therapies for the same indication

Prior Authorization

gMG — Prior Authorization & Duration Limits

For generalized myasthenia gravis (gMG) specific prior authorization: initial requests must include documented diagnosis, antibody status, disease severity (MGFA class), and MG-ADL score. Initial and reauthorization requests will be authorized for no more than 12 months.

Required for gMG initial authorization: positive serologic test for anti-AChR or anti-MuSK antibodies; MGFA Clinical Classification II, III, or IV at initiation; MG-ADL total score ≥ 5 at initiation

Background / Clinical Evidence

Inebilizumab‑cdon (Uplizna) is a CD19-directed monoclonal antibody that reduces circulating B cells, thought to act primarily through antibody‑dependent cellular cytolysis. It is FDA‑approved for neuromyelitis optica spectrum disorder (NMOSD), Immunoglobulin G4–related disease (IgG4‑RD), and generalized myasthenia gravis (gMG).

The pivotal clinical evidence supporting approval demonstrated meaningful clinical benefits in the labeled indications, including a reduction in NMOSD attacks in AQP4‑positive patients and a reduction in IgG4‑RD flares compared with placebo. For gMG, randomized data showed improvement in patient‑reported function (MG‑ADL) and other efficacy endpoints versus placebo.

Per the FDA‑labeled dosing and the policy, Uplizna is administered according to the indication‑specific schedule and should be prescribed by, or in consultation with, an appropriate specialist (neurologist for NMOSD and gMG; specialist experienced in IgG4‑RD for IgG4‑RD).

Definitions

NMOSD — definition & diagnostic summary

DefinitionNeuromyelitis optica spectrum disorder (NMOSD): diagnosis by a neurologist with history consistent with NMOSD (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)

Serology requirementPositive anti-aquaporin-4 immunoglobulin G (AQP4-IgG) antibody test required

ExclusionsMultiple sclerosis and other diagnoses must be ruled out

IgG4-RD confirmation (ACR/EULAR)

Confirmation methodPositive assessment using the ACR/EULAR classification criteria for IgG4-related disease (involvement of ≥1 organ consistent with IgG4-RD; exclusion criteria negative; inclusion criteria positive)

Denial Risk

Denial Risk — Missing NMOSD Diagnosis or Prior Therapy History

Lack of documented diagnosis meeting NMOSD criteria or missing prior therapy history (rituximab trial/intolerance where required) may lead to denial. Ensure neurologist confirmation and AQP4-IgG serology are included for NMOSD cases.

NMOSD requires neurologist confirmation of clinical syndrome (e.g., optic neuritis, acute myelitis, area postrema syndrome, etc.) and positive AQP4-IgG serology; alternative diagnoses (e.g., multiple sclerosis) must be ruled out
If NMOSD documentation or prior rituximab failure/intolerance information is absent, the request is at denial risk

Step Therapy

Step Therapy / Sequencing Requirements

Step therapy / sequencing requirements must be documented per indication. For NMOSD and IgG4-RD, trials or intolerance to rituximab (or glucocorticoid failure for IgG4-RD) are required as specified. For gMG, sequencing differs by antibody status.

NMOSD: history of failure of rituximab, or intolerance/contraindication to rituximab plus physician attestation that the same intolerance would not be expected with Uplizna
IgG4-RD: failure, contraindication, or intolerance to glucocorticoids AND either failure of rituximab or rituximab intolerance/contraindication with physician attestation
Uplizna should not be used in combination with rituximab for the same indication

Step Therapy

gMG — Step Therapy / Sequencing

For gMG, specific step therapy requirements depend on antibody status. Document prior immunosuppressive therapy history or provide required exceptions.

If anti-AChR antibody positive: history of failure of at least two immunosuppressive agents over at least 12 months, or failure of at least one immunosuppressive therapy plus ≥4 courses of plasmapheresis/plasma exchange and/or immune globulin over ≥12 months without symptom control
If anti-MuSK antibody positive: history of failure of at least one immunosuppressive agent over at least 12 months
Physician attestation required when rituximab intolerance/contraindication is cited as the reason to use Uplizna

Documentation Required

Required Clinical Documentation

Submit complete clinical documentation with initial and continuation requests. Missing charts, lab results, serology, MG-ADL scores, or prior therapy records may result in denial or delay.

Include chart notes, laboratory values (e.g., AQP4-IgG, anti-AChR, anti-MuSK serology), MG-ADL scores and MGFA class for gMG, documentation of prior therapies and dates, and specialist consultation notes
For continuation: provide documentation of clinical response (e.g., ≥2 point improvement in MG-ADL from baseline for gMG) and information on baseline immunosuppressive therapy dosing changes