ModifiedUnitedHealthcarePolicy 2025D0091I

Uplizna (inebilizumab-cdon) coverage for NMOSD and IgG4-RD

Defines UnitedHealthcare medical benefit drug policy coverage criteria for Uplizna (inebilizumab-cdon) for treatment of neuromyelitis optica spectrum disorder (NMOSD) and Immunoglobulin G4-related disease (IgG4-RD), including initial and continuation authorization requirements affecting prescribers and reviewers.

Policy Summary

PayerUnitedHealthcare

PolicyUplizna (inebilizumab-cdon) coverage for NMOSD and IgG4-RD

Policy CodePolicy 2025D0091I

Change TypeMaterial revision — added IgG4‑RD criteria and NMOSD language update

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization with documentation of diagnosis confirmation, required prior therapy history (including rituximab and glucocorticoids as applicable), specialist consultation, and FDA‑label dosing.

SourceLink

POLICY UPDATE CHANGES

Replaced language indicating 'Uplizna (inebilizumab-cdon) is proven for the treatment of NMOSD when all the [listed] criteria are met' with 'Uplizna (inebilizumab-cdon) is proven for the treatment of NMOSD'.

Revised coverage criterion to allow combination therapy exclusion only when used for the same indication: replaced 'patient is not receiving any of [the listed therapies] in combination with Uplizna' with 'patient is not receiving any of [the listed therapies] in combination with Uplizna for treatment of the same indication'.

Added language indicating Uplizna is proven and medically necessary for treatment of IgG4-RD with detailed initial and continuation criteria.

Added ICD-10 diagnosis code D89.84 to applicable codes.

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

J1823HCPCS code listed for inebilizumab

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Coverage Criteria for Uplizna (inebilizumab-cdon)

Indication-specific initial and continuation criteria

Covered when ALL of the following are met for each indication

NMOSD - Initial Therapy

Diagnosis of neuromyelitis optica spectrum disorder (NMOSD) by a neurologist confirming clinical history consistent with NMOSD (e.g., optic neuritis; acute myelitis; area postrema syndrome; acute brainstem syndrome; symptomatic narcolepsy or diencephalic syndrome with NMOSD-typical MRI lesions; symptomatic cerebral syndrome with NMOSD-typical brain lesions)
Serology and exclusions: Positive serologic test for anti-aquaporin-4 immunoglobulin G (AQP4-IgG)/NMO-IgG antibodies; and diagnosis of multiple sclerosis or other diagnoses have been ruled out
Prior rituximab requirement: Either history of failure of rituximab therapy; OR both history of intolerance/contraindication to rituximab AND physician attestation that the same intolerance or severe adverse event would not be expected to occur with Uplizna
For Medicare reviews, refer to CMS section
Relapse history: Either history of ≥1 relapse requiring rescue therapy in the previous 12 months prior to initiating Uplizna OR history of ≥2 relapses requiring rescue therapy in the previous 24 months prior to initiating Uplizna
Other initial requirements: Uplizna initiated 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 listed therapies for treatment of the same indication (multiple sclerosis disease modifying therapies, complement inhibitors, anti‑IL6 therapy, anti‑CD20 therapy); initial authorization limited to no more than 12 months

NMOSD - Continuation Therapy

Response: Documentation of positive clinical response
Dosing and combination: Uplizna dosed according to the U.S. FDA labeled dosing for NMOSD; patient is not receiving Uplizna in combination with listed therapies for treatment of the same indication (multiple sclerosis disease modifying therapies, anti‑IL6 therapy, complement inhibitors, anti‑CD20 therapy)
Authorization period: Reauthorization will be for no more than 12 months

Initial Therapy

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

IgG4-RD Initial Therapy Criteria: Diagnosis of Immunoglobulin G4-related disease (IgG4-RD) AND confirmation of IgG4-RD by a positive assessment using the ACR/EULAR classification criteria (involvement of ≥1 organ consistent with IgG4-RD; exclusion criteria negative; inclusion criteria positive) AND history of failure, contraindication, or intolerance to glucocorticoids AND one of: (a) history of failure of rituximab therapy OR (b) history of intolerance or contraindication to rituximab AND physician attests that, in their clinical opinion, the same intolerance or severe adverse event would not be expected to occur with Uplizna AND 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 the treatment of IgG4-RD AND patient is not receiving Uplizna in combination with a disease modifying therapy for the treatment of IgG4-RD (e.g., rituximab) AND initial authorization will be for no more than 12 months.

Continuation Therapy

For continuation (reauthorization), ALL of the following are required:

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

NMOSD

NMOSD Coverage Stance: Policy language revised to state that Uplizna is proven for the treatment of NMOSD.

This reflects the coverage stance change in the policy revision.

For the NMOSD indication, Uplizna must not be administered concurrently with other disease-modifying therapies for the same indication. Specifically, patients must not be receiving Uplizna in combination with multiple sclerosis disease modifying therapies (for example, dimethyl fumarate, fingolimod, ocrelizumab), anti‑IL6 therapy (e.g., tocilizumab), complement inhibitors (e.g., eculizumab, crovalimab, ravulizumab), or anti‑CD20 therapy (e.g., rituximab) for treatment of the same indication. This combination exclusion applies to both initial and continuation authorizations and supports the requirement that reauthorization be limited to no more than 12 months when criteria are met.

For the IgG4‑related disease (IgG4‑RD) indication, patients must not receive Uplizna in combination with another disease‑modifying therapy for treatment of the same indication. The policy specifically cites rituximab as an example of a disallowed combination for IgG4‑RD; this exclusion applies at both initiation and continuation and is tied to the requirement that initial and reauthorization approvals be limited to no more than 12 months.

The policy requires AQP4‑IgG seropositivity for coverage of the NMOSD indication. Clinical trial evidence showed a clear treatment benefit for inebilizumab among patients who were anti‑AQP4 antibody positive, with a large relative reduction in attacks, whereas anti‑AQP4 antibody negative patients had no evidence of benefit; therefore, the policy stipulates that patients must be AQP4‑IgG seropositive to meet NMOSD coverage criteria.

Applicable Codes

Applicable HCPCSHCPCSCovered

J1823

Injection, inebilizumab-cdon, 1 mg.

Diagnosis CodesICD-10

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

Added ICD-10 CodesICD-10

D89.84

IgG4-related disease

Provider Requirements, Prior Authorization, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization required. Providers must submit documentation that meets the indication-specific criteria for the requested indication (NMOSD or IgG4‑RD). Initial authorizations are limited to a maximum of 12 months; reauthorizations similarly require documentation of ongoing clinical benefit and are limited to no more than 12 months.

Prior authorization required for Uplizna for NMOSD and IgG4‑RD
Initial and continuation authorizations limited to ≤12 months

Prior Authorization

Prior Authorization for IgG4‑RD Requires ACR/EULAR Confirmation

For IgG4‑RD, prior authorization requires confirmation using the ACR/EULAR classification criteria and documentation of organ involvement consistent with IgG4‑RD. Requests should include evidence that exclusion criteria were considered and negative where applicable, and that inclusion criteria supporting an IgG4‑RD diagnosis are met.

ACR/EULAR classification assessment confirming IgG4‑RD
Documentation of involved organ(s) consistent with IgG4‑RD

Background and Mechanism

Inebilizumab is a CD19‑directed humanized afucosylated IgG1 monoclonal antibody that depletes B lymphocytes via antibody‑dependent cellular cytolysis. It is FDA‑indicated for adult patients with AQP4‑IgG positive neuromyelitis optica spectrum disorder (NMOSD) and for Immunoglobulin G4‑related disease (IgG4‑RD). Clinical trials demonstrated that inebilizumab reduced NMOSD attacks in AQP4‑IgG positive patients and reduced IgG4‑RD flares, supporting its approved indications.

Definitions and Key Terms

Inebilizumab mechanism (CD19-directed)

Mechanism classCD19-directed humanized afucosylated IgG1 monoclonal antibody

Primary targetB lymphocytes expressing CD19 (pre-B and mature B cells)

Effector functionBinds CD19 and results in antibody-dependent cellular cytolysis of B cells

Clinical rationaleDepletion of CD19+ B cells is presumed to mediate therapeutic effects in NMOSD and IgG4-RD

IgG4-related disease (IgG4-RD) definition

Disease categoryFibroinflammatory, immune-mediated condition that can be multiorgan or single-organ

Policy Summary

PayerUnitedHealthcare

PolicyUplizna (inebilizumab-cdon) coverage for NMOSD and IgG4-RD

Policy CodePolicy 2025D0091I

Change TypeMaterial revision — added IgG4‑RD criteria and NMOSD language update

Effective DateSep 1, 2025

Next Review DateN/A

SourceLink

On This Page

Step Therapy

Rituximab Step Requirement

A history of failure of rituximab therapy is required for Uplizna initiation unless there is documented contraindication or intolerance to rituximab. If rituximab was contraindicated or not tolerated, the physician must attest that the same intolerance or severe adverse event would not be expected with Uplizna.

History of rituximab failure OR documented contraindication/intolerance to rituximab
If intolerance/contraindication, physician attestation that similar reaction would not be expected with Uplizna

Step Therapy

Step Therapy Prerequisites for IgG4‑RD

For IgG4‑RD, step therapy prerequisites include documented failure, contraindication, or intolerance to glucocorticoids. In addition, patients must meet the rituximab step requirement (history of rituximab failure or contraindication/intolerance with attestation as above) before Uplizna is approved.

Documented failure, contraindication, or intolerance to glucocorticoids
Rituximab step (failure or contraindication/intolerance with physician attestation)

Documentation Required

Required Documentation

Providers must submit complete documentation to support medical necessity. Required materials include: diagnosis confirmation, specialist attestation (neurologist for NMOSD; specialist with expertise in IgG4‑RD for IgG4‑RD), relevant serologic testing results (e.g., AQP4‑IgG for NMOSD; IgG4 and other serologies as applicable for IgG4‑RD), prior therapy history (including rituximab and glucocorticoid trials and outcomes), dosing plan consistent with FDA labeling, and evidence of positive clinical response for continuation requests.

Diagnosis confirmation (NMOSD or IgG4‑RD)
Specialist attestation: neurologist (NMOSD) or IgG4‑RD specialist (IgG4‑RD)
Serologic test results (AQP4‑IgG for NMOSD; IgG4 and relevant tests for IgG4‑RD)
Complete prior therapy history (glucocorticoids, rituximab, other relevant therapies)
Dosing per U.S. FDA label and plan of care
Documentation of clinical response for reauthorization

Documentation Required

Required Documentation for IgG4‑RD

For IgG4‑RD specifically, documentation must include the ACR/EULAR classification confirmation (showing inclusion and exclusion criteria results), detailed description of organ involvement, prior treatments tried and outcomes (including glucocorticoids and rituximab), and name/title of the specialist providing consultation or ongoing management.

ACR/EULAR classification results with inclusion/exclusion criteria documented
Detailed organ involvement and clinical findings
Prior treatment history and response (glucocorticoids, rituximab)
Specialist name, specialty, and attestation

Denial Risk

Triggers for Potential Denial

Requests may be denied if required documentation is missing or incomplete. Common triggers for denial include absence of specialist confirmation, lack of documented prior therapy attempts or failures (including rituximab and glucocorticoids where required), missing required serology (e.g., AQP4‑IgG for NMOSD), or dosing that is inconsistent with U.S. FDA labeling.

Missing specialist confirmation or consultation note
No documentation of prior therapy trials/failures (rituximab or glucocorticoids when required)
Absent required serologic testing (AQP4‑IgG for NMOSD; IgG4/ACR‑EULAR evidence for IgG4‑RD)
Dosing not consistent with U.S. FDA labeling

Denial Risk

Denial Triggers for IgG4‑RD

IgG4‑RD requests specifically may be denied if the ACR/EULAR assessment is not provided or does not support the diagnosis, if organ involvement is not detailed, or if there is no documentation of glucocorticoid failure/contraindication or the required rituximab step (failure or documented contraindication/intolerance with physician attestation).

Missing or non‑confirmatory ACR/EULAR assessment
Insufficient documentation of organ involvement
No documentation of glucocorticoid failure/contraindication
No rituximab failure or contraindication/intolerance with attestation