ModifiedUnitedHealthcarePolicy IEXD0091.09

Uplizna (inebilizumab-cdon) coverage for NMOSD and IgG4-related disease

Defines UnitedHealthcare medical necessity criteria, prior authorization and coverage conditions for Uplizna (inebilizumab-cdon) for treatment of neuromyelitis optica spectrum disorder (NMOSD) and immunoglobulin G4-related disease (IgG4-RD) affecting members covered by the specified benefit.

Policy Summary

PayerUnitedHealthcare

PolicyUplizna (inebilizumab-cdon) coverage for NMOSD and IgG4-related disease

Policy CodePolicy IEXD0091.09

Change TypeModified coverage criteria and added IgG4‑RD initial/continuation requirementsreauthorization limits added

Effective Date09/01/2025

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of indication, prior-therapy history, specialist involvement, FDA‑label dosing, and evidence of positive clinical response for reauthorization.

SourceLink

POLICY UPDATE CHANGES

Replaced criterion requiring that the patient is not receiving any of the listed therapies in combination with Uplizna with language specifying the therapies are not being used in combination with Uplizna for treatment of the same indication.

Added coverage criteria making Uplizna proven and medically necessary for IgG4-RD when specified diagnostic and prior-therapy criteria are met.

Initial and continuation authorization limited to no more than 12 months.

Documentation of positive clinical response is required for continuation of therapy.

Uplizna is dosed according to the U.S. FDA labeled dosing for IgG4-RD.

Prescriber must be, or consult with, a specialist with expertise in treating IgG4-RD; Uplizna must not be given in combination with another disease-modifying therapy for IgG4-RD (e.g., rituximab).

ICD-10 diagnosis code D89.84 was added.

09/01/2025

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Coverage Criteria for Uplizna (inebilizumab-cdon)

NMOSD — Initial and Continuation Therapy

Covered when ALL of the following are met

NMOSD initial therapy basic requirements: Diagnosis of neuromyelitis optica spectrum disorder (NMOSD) by a neurologist confirming compatible clinical syndromes (e.g., optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic diencephalic or cerebral syndromes) AND positive serologic test for anti‑aquaporin‑4 immunoglobulin G (AQP4‑IgG)/NMO‑IgG antibodies AND multiple sclerosis and other alternate diagnoses have been ruled out

supporting clinical history per policy

Prior therapy requirement for NMOSD: Either history of failure of rituximab therapy OR both history of intolerance or contraindication to rituximab AND physician attestation that the same intolerance or severe adverse event would not be expected to occur with Uplizna

step therapy requirement

Relapse history requirement: Either history of one or more relapses that required rescue therapy during the previous 12 months prior to initiating Uplizna OR history of two or more relapses that required rescue therapy during the previous 24 months prior to initiating Uplizna

defines attack history prerequisite

Administration and prescriber limits: Uplizna is initiated and continued according to the U.S. FDA labeled dosing for NMOSD; prescribed by, or in consultation with, a neurologist; patient is not receiving Uplizna in combination with any of the listed therapies for treatment of the same indication (e.g., multiple sclerosis DMTs such as dimethyl fumarate, fingolimod, ocrelizumab; complement inhibitors such as eculizumab, crovalimab, ravulizumab; anti‑IL6 therapy such as tocilizumab; anti‑CD20 therapy such as rituximab); initial authorization will be for no more than 12 months; reauthorization will be for no more than 12 months with documentation of positive clinical response

combination therapy exclusions and authorization duration specified

IgG4-RD — Initial and Continuation Therapy

Covered when ALL of the following are met

IgG4-RD diagnostic confirmation: Diagnosis of Immunoglobulin G4‑related disease (IgG4‑RD) AND confirmation by a positive assessment using the ACR/EULAR classification criteria demonstrated by: involvement of ≥1 organ consistent with IgG4‑RD; exclusion criteria negative and consistent with IgG4‑RD; and inclusion criteria positive from clinical, serologic, radiology, or pathology assessments

ACR/EULAR classification criteria required

Prior therapy requirement for IgG4-RD: History of failure, contraindication, or intolerance to glucocorticoids AND one of the following: history of failure of rituximab therapy OR both history of intolerance or contraindication to rituximab AND physician attestation that the same intolerance/severe adverse event would not be expected to occur with Uplizna

step therapy requiring glucocorticoid then rituximab pathway

Administration and prescriber limits for IgG4-RD: Uplizna is initiated according to the U.S. FDA labeled dosing for IgG4‑RD; prescribed by, or in consultation with, a specialist with expertise in IgG4‑RD; patient is not receiving Uplizna in combination with a disease‑modifying therapy for the treatment of IgG4‑RD (e.g., rituximab); initial authorization will be for no more than 12 months; reauthorization will be for no more than 12 months with documentation of positive clinical response

Initial Therapy — IgG4-RD

Uplizna is considered proven and medically necessary for IgG4-RD when ALL of the following are met:

Initial Therapy criteria: Diagnosis of IgG4‑RD; confirmation by ACR/EULAR classification criteria demonstrated by: involvement of ≥1 organ consistent with IgG4‑RD; exclusion criteria negative; inclusion criteria positive; history of failure, contraindication, or intolerance to glucocorticoids; and one of: history of failure of rituximab therapy OR history of intolerance/contraindication to rituximab with physician attestation that the same intolerance/severe adverse event would not be expected with Uplizna; Uplizna initiated per U.S. FDA labeled dosing for IgG4‑RD; prescribed by or in consultation with a specialist experienced in IgG4‑RD; patient is not receiving Uplizna in combination with a disease‑modifying therapy for treatment of IgG4‑RD (e.g., rituximab); initial authorization ≤ 12 months

Initial authorization and step therapy details per policy

Continuation Therapy — IgG4-RD

For continuation of therapy for IgG4-RD, ALL of the following must be met:

Continuation Therapy criteria: Documentation of positive clinical response; Uplizna dosed according to the U.S. FDA labeled dosing for IgG4‑RD; prescribed by, or in consultation with, a specialist with expertise in IgG4‑RD; patient is not receiving Uplizna in combination with a disease‑modifying therapy for treatment of IgG4‑RD (e.g., rituximab); reauthorization will be for no more than 12 months

Continuation requires documented clinical benefit, dosing per FDA, specialist involvement, no concomitant DMT

NMOSD — Combination therapy clarification

NMOSD coverage language revised:

Combination therapy clarification for NMOSD: Patient must not be receiving any of the listed therapies in combination with Uplizna for treatment of the same indication (clarified from prior wording that broadly prohibited combination use)

Clarification replaces prior absolute prohibition language; applies to NMOSD

Continuation / Reauthorization Criteria

Covered when ALL of the following are met:

Continuation/Reauthorization: Documentation of positive clinical response is provided

Required for continuation/reauthorization

Dosing: Uplizna is dosed according to the U.S. FDA labeled dosing for IgG4‑RD

Dosing must follow FDA label

Prescriber: Prescribed by, or in consultation with, a specialist with expertise in the treatment of IgG4‑RD

Specialist involvement required

Concurrent therapy exclusion: Patient is not receiving Uplizna in combination with a disease‑modifying therapy for IgG4‑RD (e.g., rituximab)

Initial and Reauthorization Coverage Criteria

Covered when ALL of the following are met

Specialist involvement: Prescribed by, or in consultation with, a specialist with expertise in the treatment of IgG4‑RD

Prescriber requirement

No concomitant DMT: Patient is not receiving Uplizna in combination with a disease‑modifying therapy for the treatment of IgG4‑RD (e.g., rituximab)

Concurrent DMT prohibited

Dosing standard: Uplizna is dosed according to the U.S. FDA labeled dosing for IgG4‑RD

Follow FDA labeled dosing

Reauthorization interval: Reauthorization will be for no more than 12 months.

Initial and Continuation Therapy Requirements

Covered when ALL of the following are met

Specialist: Prescribed by, or in consultation with, a specialist with expertise in the treatment of IgG4‑related disease

Specialist involvement required

Dosing: Uplizna is dosed according to the U.S. FDA labeled dosing for IgG4‑RD

Follow FDA labeled dosing

No concomitant DMT: Patient is not receiving Uplizna in combination with another disease‑modifying therapy for IgG4‑RD (e.g., rituximab)

Concurrent DMT prohibited

Continuation response: Documentation of positive clinical response is required for continuation of therapy

Use of Uplizna in combination with other therapies for the same indication is explicitly excluded. For NMOSD, the policy requires that the patient is not receiving Uplizna in combination with any of the following for treatment of the same indication: multiple sclerosis disease-modifying therapies (e.g., dimethyl fumarate, fingolimod, ocrelizumab), complement inhibitors (e.g., eculizumab, crovalimab, ravulizumab), anti-IL6 therapy (e.g., tocilizumab), or anti-CD20 therapy (e.g., rituximab).

Patients with IgG4-related disease are excluded from coverage if they are receiving Uplizna in combination with a disease-modifying therapy for treatment of IgG4-RD (e.g., rituximab). Initial and continuation criteria require that Uplizna not be used concurrently with another DMT for the same indication.

The policy disallows combination therapy for IgG4-RD: Uplizna must not be given in combination with another disease-modifying therapy for IgG4-related disease (example: rituximab). Requests noting concurrent DMT use for the same indication may be denied.

The combination-therapy exclusion for IgG4-RD is reiterated in the policy history: the patient must not be receiving Uplizna in combination with a disease-modifying therapy for the treatment of IgG4-related disease (e.g., rituximab).

Continuation language for IgG4-RD repeats the restriction: for reauthorization the patient must not be receiving Uplizna in combination with another disease-modifying therapy for IgG4-RD (for example, rituximab), and documentation of clinical response is required.

Patient must not be receiving Uplizna in combination with another disease‑modifying therapy for IgG4‑RD (e.g., rituximab).

Revision-history notes consistently state that use of Uplizna in combination with a disease‑modifying therapy for the treatment of IgG4-related disease (e.g., rituximab) is disallowed.

In the pivotal NMOSD trial, benefit was restricted to the AQP4‑IgG seropositive population; patients who were AQP4‑IgG seronegative showed no evidence of benefit in that study and therefore lack of AQP4‑IgG positivity may not meet the policy diagnostic criteria for coverage.

Coverage may be denied when Uplizna is prescribed in combination with another disease‑modifying therapy for IgG4‑RD (e.g., rituximab) or when required prior‑therapy documentation (such as prior rituximab failure or documented intolerance/contraindication with physician attestation) is not provided.

Continuation or reauthorization requests that do not include documentation of a positive clinical response to Uplizna may be considered not medically necessary and are subject to denial.

If clinical or administrative questions arise regarding these combination‑therapy restrictions, include clear documentation of current therapies, indication for each agent, and any physician attestations supporting non‑use of excluded concurrent therapies.

Applicable Billing and Diagnosis Codes

HCPCS CodesHCPCS

J1823

Injection, inebilizumab-cdon, 1 mg

ICD-10 CodesICD-10

D89.84	IgG4-related disease
G36.0	Neuromyelitis optica [Devic]

Applicable Codesmixed

No codes listed

Applicable ICD-10 CodesICD-10Covered

D89.84

Newly added ICD-10 diagnosis code (IgG4-related disease as added to Applicable Codes)

Applicable ICD-10 CodesICD-10

D89.84

ICD-10 diagnosis code added (document cites addition of D89.84)

Applicable Codesmixed

No codes listed

Applicable Codesmixed

No codes listed

Provider Requirements, Prior Authorization, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior Authorization Required — Prior authorization (PA) is required for initial and continuation/reauthorization of Uplizna (inebilizumab-cdon). Initial and continuation/reauthorizations will be limited to no more than 12 months. PA requests must include indication-specific documentation, prior‑therapy history (including step-therapy or prior biologic use), evidence of adherence to U.S. FDA labeled dosing, and specialist involvement when indicated.

Initial and reauthorization periods limited to ≤ 12 months
PA must document indication, prior therapies, and FDA dosing adherence
Continuation/reauthorization requires evidence of positive clinical response

Documentation Required

Prior Authorization Requirements — Initial Authorization

Initial authorization requirements vary by indication. For NMOSD, documentation must include neurologist-confirmed diagnosis (including compatible clinical history and positive AQP4‑IgG), prior rituximab failure or documented rituximab intolerance/contraindication, evidence of relapses as specified, initiation per U.S. FDA labeled dosing for NMOSD, and prescription by or in consultation with a neurologist. For IgG4‑RD, documentation must include diagnosis confirmation by ACR/EULAR classification criteria, history of failure/intolerance/contraindication to glucocorticoids, either prior rituximab failure or documented rituximab intolerance/contraindication with clinician attestation that the same intolerance would not be expected with Uplizna, initiation per U.S. FDA labeled dosing for IgG4‑RD, and prescription by or in consultation with a specialist experienced in IgG4‑RD.

Background and Clinical Context

Uplizna (inebilizumab‑cdon) is a CD19‑directed humanized afucosylated IgG1 monoclonal antibody that exerts its therapeutic effect by binding CD19 on B cells and inducing antibody‑dependent cellular cytolysis. This B‑cell targeting mechanism underlies its indications and clinical rationale for use in neuromyelitis optica spectrum disorder (NMOSD) and immunoglobulin G4‑related disease (IgG4‑RD).

Key Definitions and Diagnostic Criteria

NMOSD diagnostic features — key clinical features to confirm NMOSD diagnosis

Core diagnostic featuresOptic neuritis; acute myelitis; area postrema syndrome (episodes of otherwise unexplained hiccups or nausea/vomiting); acute brainstem syndrome; symptomatic narcolepsy or diencephalic syndrome with NMOSD-typical diencephalic MRI lesions; symptomatic cerebral syndrome with NMOSD-typical brain lesions

Serology requirementPositive serologic test for anti-aquaporin-4 immunoglobulin G (AQP4-IgG)/NMO-IgG antibodies

Exclusion requirementDiagnosis of multiple sclerosis or other alternative diagnoses must be ruled out

Relapse history thresholdsEither ≥1 relapse requiring rescue therapy in prior 12 months OR ≥2 relapses requiring rescue therapy in prior 24 months

Prescriber and dosingDiagnosis confirmed by a neurologist; Uplizna must be initiated according to U.S. FDA labeled dosing for NMOSD

Policy Revision History

Policy Summary

PayerUnitedHealthcare

PolicyUplizna (inebilizumab-cdon) coverage for NMOSD and IgG4-related disease

Policy CodePolicy IEXD0091.09

Change TypeModified coverage criteria and added IgG4‑RD initial/continuation requirementsreauthorization limits added

Effective Date09/01/2025

Next Review DateN/A

SourceLink

On This Page

Documentation Required

Prior Authorization Requirements — Continuation/Reauthorization

Continuation and reauthorization requests must include documentation of a positive clinical response to Uplizna, confirmation that dosing follows the U.S. FDA labeled dosing for the relevant indication, and evidence that the prescriber is a specialist or has consulted with a specialist when required (neurologist for NMOSD; specialist with expertise in IgG4‑RD for IgG4‑RD). Reauthorizations will be granted for no more than 12 months.

Documentation of positive clinical response for continuation/reauthorization
Dosing must follow U.S. FDA labeled dosing for the treated indication
Prescriber must be, or consult with, an appropriate specialist
Reauthorization limited to ≤ 12 months

Step Therapy

Step Therapy / Prior Biologic Requirement

Step‑therapy/previous biologic requirements: where specified by indication, a prior trial and failure of rituximab is required (or documented intolerance/contraindication to rituximab plus clinician attestation that the same intolerance would not be expected with Uplizna). For IgG4‑RD, a history of failure, contraindication, or intolerance to glucocorticoids is also required prior to Uplizna.

Prior rituximab failure required or rituximab intolerance/contraindication with attestation
IgG4‑RD: prior glucocorticoid failure/intolerance required

Denial Risk

Concurrent Therapy Restriction

Concurrent therapy restriction — Uplizna should not be used in combination with other disease‑modifying therapies (DMTs) for the same indication. Coverage may be denied if Uplizna is prescribed concomitantly with other DMTs for the same treated condition (examples include rituximab and other anti‑CD20 therapies, multiple sclerosis DMTs, complement inhibitors, and anti‑IL6 therapy).

Do not combine Uplizna with anti‑CD20 therapy (e.g., rituximab) for the same indication
Do not combine with MS DMTs (e.g., dimethyl fumarate, fingolimod, ocrelizumab)
Do not combine with complement inhibitors or anti‑IL6 agents

Denial Risk

Triggers for Denial

Triggers for denial — Requests may be denied if required diagnostic criteria or classification confirmation are not provided; required prior therapies or step‑therapy criteria are not documented; dosing does not follow U.S. FDA labeled dosing for the indication; prescriber is not or has not consulted with an appropriate specialist when required; or Uplizna is prescribed in combination with another disease‑modifying therapy for the same indication.

Missing diagnostic/classification documentation (e.g., ACR/EULAR for IgG4‑RD; neurologist confirmation and AQP4‑IgG for NMOSD)
No documentation of required prior therapies or rituximab failure/intolerance
Lack of evidence of FDA‑labeled dosing or specialist involvement
Concurrent use with another DMT for the same indication (e.g., rituximab)

Denial Risk

Potential Denial Triggers for Continuation

Potential denial triggers for continuation — Continuation or reauthorization requests may be denied if there is no documentation of a positive clinical response, if dosing deviates from U.S. FDA labeled dosing for the indication, if the prescriber is not a specialist nor has consulted a specialist when required, or if the patient is receiving concomitant disease‑modifying therapy for the same indication.

Absence of documentation demonstrating positive clinical benefit
Dosing inconsistent with U.S. FDA labeled dosing for the indication
No specialist involvement or consultation where required
Concurrent DMT use for the same indication

Note

Provider Actions — Documentation and Submission

Provider actions summary — Submit complete clinical documentation with PA requests: diagnosis confirmation (including required lab/serology or classification scoring), prior‑therapy history and outcomes (including rituximab and glucocorticoid trials where applicable), objective evidence of clinical response for continuation requests, and a dosing schedule consistent with U.S. FDA labeling. Ensure the prescribing clinician is the appropriate specialist or documents a consultation with one. Failure to supply required documentation or evidence of disallowed combination therapy may result in denial.

Include diagnostic tests/results (e.g., AQP4‑IgG for NMOSD; ACR/EULAR assessment for IgG4‑RD)
Provide prior therapy details and clinician attestations when applicable
Provide objective measures or narrative documenting positive clinical response for continuation
Confirm prescriber specialty or include specialist consultation note
Do not prescribe Uplizna with another DMT for the same indication

Note

Additional Notes

Notes and placeholders — Some historical/revision notes indicate 'Applicable Codes' are referenced elsewhere in the policy but are not enumerated in this excerpt. Also, certain historical chunks contain no additional documentation requirements beyond those above. If no step therapy requirement is listed for a specific benefit or population, follow the criteria shown for the indicated diagnosis.

Applicable HCPCS: J1823 (see Applicable Codes section of policy)
When the excerpt indicates 'no step therapy requirements', interpret that as no additional step requirement beyond the criteria presented

Required confirmationDiagnosis of IgG4-RD must be confirmed by a positive assessment using the ACR/EULAR classification criteria

Organ involvementInvolvement of ≥1 organ in a manner consistent with IgG4-RD must be demonstrated

Exclusion criteriaExclusion criteria must be negative and consistent with an IgG4-RD diagnosis (e.g., clinical findings, serology, radiology, pathology)

Evidence sources for inclusion criteriaInclusion criteria must be positive based on clinical, serologic, radiologic, or pathologic assessments

Prescriber and dosing noteInitial therapy must be prescribed by or in consultation with a specialist experienced in IgG4-RD and initiated per U.S. FDA labeled dosing

ACR/EULAR classification criteria — structured inclusion/exclusion criteria used to confirm IgG4-RD diagnosis

DefinitionACR/EULAR classification criteria are a structured set of inclusion and exclusion criteria used to confirm a diagnosis of IgG4-related disease, including demonstration of organ involvement, negative exclusion criteria, and positive inclusion criteria from clinical, serologic, radiologic, or pathologic assessments

Use in policyRequired as confirmation for initial authorization of Uplizna for IgG4-RD

DocumentationDocumentation must show the criteria assessment results (organ involvement, exclusion criteria negative, inclusion criteria positive)