ModifiedConnectiCarePolicy C20171-A

Uplizna (inebilizumab-cdon) Coverage for NMOSD, IgG4-RD, and Generalized Myasthenia Gravis

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This policy governs prior authorization coverage for intravenous Uplizna in adults with neuromyelitis optica spectrum disorder, immunoglobulin G4-related disease, or generalized myasthenia gravis. Coverage requires diagnosis-specific clinical documentation, infection and concomitant-therapy screening, response or disease-activity monitoring, and applicable site-of-care requirements.

Policy Summary

PayerConnectiCare

PolicyUplizna (inebilizumab-cdon) Coverage for NMOSD, IgG4-RD, and Generalized Myasthenia Gravis

Policy CodePolicy C20171-A

Change TypeModified

Effective DateApr 1, 2026

Next Review DateJul 1, 2026

Key ActionSubmit documentation of the applicable diagnosis and required disease-specific criteria with the prior authorization request.

SourceLink

POLICY UPDATE CHANGES

The policy revision history identifies updates to diagnosis requirements, required medical information, continuation therapy, prescriber requirements, FDA-approved uses, duration of approval, drug class, and other special considerations.

3FDA-approved adult indications addressed

6 monthsInitial authorization duration

12 monthsContinuation authorization duration

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ModifiedConnectiCarePolicy C20171-A

Uplizna (inebilizumab-cdon) Coverage for NMOSD, IgG4-RD, and Generalized Myasthenia Gravis

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Policy Summary

PayerConnectiCare

PolicyUplizna (inebilizumab-cdon) Coverage for NMOSD, IgG4-RD, and Generalized Myasthenia Gravis

Policy CodePolicy C20171-A

Change TypeModified

Effective DateApr 1, 2026

Next Review DateJul 1, 2026

Key ActionSubmit documentation of the applicable diagnosis and required disease-specific criteria with the prior authorization request.

SourceLink

POLICY UPDATE CHANGES

3FDA-approved adult indications addressed

6 monthsInitial authorization duration

12 monthsContinuation authorization duration

300 mg IVInitial infusion dose

≥85%Continuation adherence threshold

18+Minimum age requirement

Coverage Criteria

NMOSD initial therapy

Covered for NMOSD when ALL of the following are met:

ALL of the following
- The member has a documented diagnosis of neuromyelitis optica spectrum disorder (NMOSD).
- The diagnosis is confirmed by a positive serum anti-aquaporin-4 antibody (AQP4-IgG) test.
- At least one core clinical characteristic is documented: optic neuritis, acute myelitis, acute postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy, acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions, or symptomatic cerebral syndrome with NMOSD-typical brain lesions.
- The member does not have an active or latent untreated infection, including clinically important localized infections, according to the FDA label.
- The member is not receiving prohibited concomitant immunosuppressive therapy and will not use Uplizna with a complement inhibitor or anti-CD20-directed antibody therapy.
- ALL of the following
  - Relapse history
    At least 1 relapse requiring rescue therapy occurred within the previous 12 months.
    At least 2 relapses requiring rescue therapy occurred within the previous 2 years.
  - Baseline Expanded Disability Status Scale (EDSS) score is documented.EDSS ≤ 8
  - Baseline relapse rate and visual acuity are documented.

NMOSD continuation therapy

Covered for NMOSD continuation when ALL of the following are met:

Adherence
- Adherence to therapy is at least 85% as verified by the prescriber or medication fill history.≥85%
- Adherence is below 85% because surgery or treatment of an infection required temporary discontinuation.
Therapy has resulted in clinical improvement or stabilization from baseline or the previous authorization.
Response may be demonstrated by relapse frequency, EDSS, reduced hospitalizations, reduced plasma exchange treatments, or visual acuity.
There is no evidence of intolerable adverse effects or drug toxicity, including serious infusion reactions or serious systemic infections.

IgG4-RD initial therapy

Covered for IgG4-RD when ALL of the following are met:

The member has a documented diagnosis of immunoglobulin G4-related disease (IgG4-RD).
The member does not have an active or latent untreated infection, including clinically important localized infections, according to the FDA label.
IgG4-RD affects at least 2 organs or sites at any time during the disease course.≥2 organs/sites
Baseline disease activity and treatment goals are documented for evaluation of efficacy at renewal.
The member has an inadequate response or contraindication to glucocorticoid therapy.
Glucocorticoid-refractory disease includes failure to achieve symptom relief, reduce mass or organ size, improve organ function, or adequately decrease serum IgG4 concentrations. It also includes inability to reduce glucocorticoid dosage below 5 mg daily without a disease flare or worsening symptoms.

IgG4-RD continuation therapy

Covered for IgG4-RD continuation when ALL of the following are met:

Adherence
- Adherence to therapy is at least 85% as verified by the prescriber or medication fill history.≥85%
- Adherence is below 85% because surgery or treatment of an infection required temporary discontinuation.
Therapy has produced a positive clinical response.
Positive response is demonstrated by decreased frequency or severity of flares and/or improvement in signs and symptoms.
The prescriber attests to ongoing monitoring for infection, including tuberculosis and hepatitis B reactivation, according to the FDA label.

Generalized myasthenia gravis initial therapy

Covered for generalized myasthenia gravis when ALL of the following are met:

gMG initial therapy

The member has a documented diagnosis of generalized myasthenia gravis.
ALL of the following
- The member has Myasthenia Gravis Foundation of America (MGFA) Clinical Classification class II, III, or IV.MGFA class II, III, or IV
- Positive serologic test
  - Positive binding anti-acetylcholine receptor antibody (AChR-ab) testing is documented.

Generalized myasthenia gravis continuation therapy

Covered for generalized myasthenia gravis continuation when ALL of the following are met:

gMG continuation therapy

Adherence
- Adherence to therapy is at least 85% as verified by the prescriber or medication fill history.≥85%
- Adherence is below 85% because surgery or treatment of an infection required temporary discontinuation.
There is no evidence of intolerable adverse effects or drug toxicity, including serious infusion reactions or serious systemic infections.
Therapy has produced low disease activity or clinical improvement.
Response may be demonstrated by improvement from baseline in MG-ADL score, reduction in signs and symptoms of myasthenia gravis, or stabilization, reduction, or discontinuation of baseline immunosuppressive therapy.

Coverage requires screening for prohibited concomitant therapy. Uplizna should not be used with other specified immunosuppressants, including maintenance corticosteroids except permitted premedication, rescue therapy, or doses of 20 mg/day or less; complement inhibitors such as eculizumab or ravulizumab; or anti-CD20-directed antibodies such as rituximab. For generalized myasthenia gravis, concurrent use with Rystiggo, Soliris, Ultomiris, Vyvgart or Vyvgart Hytrulo, or Zilbrysq is not permitted.

No compendial approved off-label uses are listed for Uplizna. Uses outside the policy’s recognized indications are considered experimental or investigational and are handled under the applicable off-label policy.

Uplizna is contraindicated, and coverage may be denied or discontinued, for a previous life-threatening infusion reaction to Uplizna, active hepatitis B infection, or active or untreated latent tuberculosis.

Routine immunizations should be administered according to immunization guidelines at least 4 weeks before Uplizna initiation. Live and live-attenuated vaccines are not recommended during treatment or until B-cell repletion; safety after Uplizna therapy has not been established.

Coding and Clinical Thresholds

HCPCS CODEHCPCS

J1823

Injection, inebilizumab-cdon, 1 mg

NMOSD relapse history

Recent relapse thresholdAt least 1 relapse requiring rescue therapy within the previous 12 months

Two-year relapse thresholdAt least 2 relapses requiring rescue therapy within the previous 2 years

Qualifying rescue therapyRelapse treatment includes intravenous corticosteroids and/or plasma exchange

NMOSD baseline EDSS

AssessmentBaseline Expanded Disability Status Scale (EDSS) score

Maximum qualifying scoreEDSS ≤ 8

Documentation

Provider Requirements and Action Items

Prior Authorization

Prior Authorization and Duration

Prior authorization is required for Uplizna (inebilizumab-cdon). Initial authorization is approved for 6 months; continuation authorizations are approved for 12 months.

Initial authorization: 6 months
Continuation authorization: 12 months

Step Therapy

gMG Prerequisite Therapy

For gMG, document that the member has trialed both pyridostigmine and formulary glucocorticoids before initiating Uplizna.

The trial must be for at least 2 weeks, unless the member has a serious side effect or contraindication.
Document the treatment response and the reason the prerequisite therapy was inadequate, not tolerated, or contraindicated.

Clinical Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, relapsing autoimmune disorder affecting the brain and spinal cord. It is characterized primarily by optic neuritis and myelitis, with relapses that may result in permanent visual impairment and spinal cord disability.

Definitions

Rescue therapy

Intravenous corticosteroidsRescue therapy includes intravenous corticosteroids

Plasma exchangeRescue therapy includes plasma exchange

Combined useThe policy defines rescue therapy as intravenous corticosteroids and/or plasma exchange

Refractory to glucocorticoids

Symptom responseFailure to achieve symptom relief with glucocorticoid therapy

Organ responseFailure to reduce mass or organ size or improve organ function

Serum IgG4 response

Initial Therapy Criteria

Initial therapy

Initial therapy is covered only when the member is at least 18 years old and meets ALL applicable criteria for ONE of the following indications:

ONE covered initial indication

NMOSD
- Documented NMOSD with positive serum anti-AQP4 antibody testing and at least one core clinical characteristic.
- Relapse history
  - At least 1 relapse requiring rescue therapy within the previous 12 months.
  - At least 2 relapses requiring rescue therapy within the previous 2 years.

Continuation Criteria

Continuation therapy

Continuation coverage requires ALL applicable criteria:

Continuation and renewal requirements

Adherence
- Adherence to therapy is at least 85% as verified by the prescriber or medication fill history.≥85%
- Adherence is below 85% because surgery or treatment of an infection required temporary discontinuation.
Clinical response or disease control
- For NMOSD, therapy has produced clinical improvement or stabilization from baseline or the previous authorization, demonstrated by relapse frequency, EDSS, hospitalizations, plasma exchange use, or visual acuity.

Step Therapy Requirements

Step	Required prior therapy	Duration	Coverage requirement
1
Pyridostigmine and formulary glucocorticoids
2 weeks
Inadequate treatment response, serious side effects, or contraindication before Uplizna for generalized myasthenia gravis

Step	Required prior therapy	Failure or exception criteria	Coverage requirement
1
Glucocorticoid therapy
Inadequate response or documented contraindication. Refractory disease includes failure of symptom relief, reduction in mass or organ size, improvement in organ function, or adequate reduction in serum IgG4; it also includes inability to reduce glucocorticoids below 5 mg/day without disease flare or worsening symptoms.
Required before Uplizna for immunoglobulin G4-related disease

Dose and Quantity Limits

Uplizna (inebilizumab-cdon)

Initial infusionOne 300 mg intravenous infusion

Second infusionA second 300 mg intravenous infusion 2 weeks after the initial dose

Ongoing scheduleOne 300 mg intravenous infusion every 6 months, beginning 6 months from the first infusion

Site-of-Care Requirements

Billing Rule

Use an approved non-hospital infusion site

Administer infused Uplizna in a non-hospital facility-based location for pharmacy or medical benefit coverage, in accordance with the applicable site-of-care program and utilization management policy.

Recommended setting: non-hospital facility-based infusion location
The applicable site-of-care utilization management policy applies

Policy Summary

PayerConnectiCare

PolicyUplizna (inebilizumab-cdon) Coverage for NMOSD, IgG4-RD, and Generalized Myasthenia Gravis

Policy CodePolicy C20171-A

Change TypeModified

Effective DateApr 1, 2026

Next Review DateJul 1, 2026

Key ActionSubmit documentation of the applicable diagnosis and required disease-specific criteria with the prior authorization request.

SourceLink

On This Page

The prescriber attests to ongoing monitoring for infection, including tuberculosis and hepatitis B reactivation, according to the FDA label.

The member is not receiving prohibited concomitant immunosuppressive therapy or an anti-CD20-directed antibody therapy.

Positive anti-muscle-specific tyrosine kinase (MuSK) antibody testing is documented.

The member's MG-ADL total score or another treatment-efficacy monitoring measure is documented.

The member does not have an active or latent untreated infection, including clinically important localized infections, according to the FDA label.

The member has had an inadequate treatment response, serious side effects, or a contraindication to both pyridostigmine and formulary glucocorticoids.2-week trial

Inebilizumab will not be used concurrently with Rystiggo, Soliris, Ultomiris, Vyvgart or Vyvgart Hytrulo, or Zilbrysq.

The prescriber attests to ongoing monitoring for infection, including tuberculosis and hepatitis B reactivation, according to the FDA label.

The member’s baseline EDSS score must be documented

IgG4-RD organ involvement

Minimum involvementAt least 2 organs or sites affected

Disease-course timingInvolvement may have occurred at any time during the disease course

ExamplesExamples include the pancreas, lungs, kidneys, lacrimal glands, major salivary glands, retroperitoneum, aorta, or thyroid gland

Glucocorticoid dependence

Dose-reduction requirementGlucocorticoid dose cannot be reduced to less than 5 mg/day

Flare thresholdDose reduction causes a disease flare or worsening symptoms

Policy contextThis is considered glucocorticoid dependence

Continuation adherence

Minimum adherenceAt least 85% of therapy

VerificationAdherence is verified by the prescriber or the member’s medication fill history

ExceptionLower adherence is permitted when surgery or treatment of an infection required temporary discontinuation

Treatment age

Minimum age18 years

Eligible populationAdults

Coverage restrictionCoverage is limited to members 18 years of age and older

Step Therapy

IgG4-RD Glucocorticoid Prerequisite

For IgG4-RD, document an inadequate response to or contraindication to glucocorticoid therapy. Refractory disease includes failure to achieve symptom relief, reduction in mass or organ size, improved organ function, or an adequate decrease in serum IgG4 concentrations with glucocorticoid monotherapy.

Glucocorticoid-dependent disease qualifies when the member cannot reduce glucocorticoids to less than 5 mg/day without a disease flare or worsening symptoms.
Include the specific glucocorticoid course, response, adverse effect, or contraindication in the request.

Documentation Required

Diagnosis and Baseline Documentation

Submit diagnosis-specific records and baseline documentation supporting the requested indication. NMOSD requires the applicable antibody, clinical, relapse, disability, and visual-status records; IgG4-RD requires multisite organ involvement and baseline disease activity and treatment goals.

NMOSD: documented diagnosis; positive serum anti-aquaporin-4 antibody (AQP4-IgG); at least one core characteristic such as optic neuritis, acute myelitis, acute postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy, acute diencephalic syndrome with typical MRI lesions, or symptomatic cerebral syndrome with typical brain lesions.
NMOSD baseline: one or more relapses requiring rescue therapy within the prior 12 months, or at least two such relapses within the prior 2 years; baseline EDSS score of 8 or less; and baseline relapse rate and visual acuity. Rescue therapy includes IV corticosteroids and/or plasma exchange.
IgG4-RD: documented diagnosis and involvement of at least 2 organs or sites at any time during the disease course, with baseline disease activity evaluation and treatment goals, such as baseline symptoms and flare frequency.

Documentation Required

gMG Clinical Documentation

For gMG, submit documentation establishing generalized disease severity, antibody status, and the measure that will be used to monitor efficacy.

Document a diagnosis of generalized myasthenia gravis and MGFA Clinical Classification II, III, or IV.
Confirm seropositivity with binding anti-acetylcholine receptor antibodies (AChR-Ab) or anti-muscle-specific tyrosine kinase (MuSK) antibodies.
Provide the baseline Myasthenia Gravis-Specific Activities of Daily Living (MG-ADL) total score, or another defined measure for treatment-plan efficacy monitoring.

Documentation Required

IgG4-RD Documentation

For IgG4-RD, provide records supporting the extent and activity of disease and the goals against which Uplizna response will be assessed.

Document IgG4-RD involvement of at least 2 organs or sites, such as the pancreas, lungs, kidneys, lacrimal glands, major salivary glands, retroperitoneum, aorta, or thyroid gland.
Include a prescriber assessment of baseline disease activity, symptoms, and flare frequency.
State the treatment goals and the outcomes that will be reviewed at renewal.

Documentation Required

Continuation and Renewal Documentation

For renewal, document adherence, clinical benefit or stabilization, tolerability, and ongoing safety monitoring for the applicable indication.

Document adherence of at least 85% by prescriber verification or medication fill history. Adherence below 85% may be accepted when temporary discontinuation was required for surgery or infection treatment.
NMOSD: document improvement or stabilization from baseline or the prior authorization, including relapse frequency, EDSS, hospitalizations, plasma exchange requirements, or visual acuity.
IgG4-RD: document a positive clinical response through decreased frequency or severity of flares and/or improvement in signs and symptoms.
gMG: document low disease activity or improvement, including an improved MG-ADL score, reduced signs and symptoms, or stabilization, reduction, or discontinuation of baseline immunosuppressive therapy.
Document no intolerable adverse effects or drug toxicity and ongoing monitoring for infection, including tuberculosis and hepatitis B reactivation, according to the FDA label.

Documentation Required

Prescriber Qualifications

Uplizna must be prescribed by, or in consultation with, a qualified specialist experienced in treating the applicable disease. If prescribed in consultation, submit the consultation notes with the initial request and each reauthorization.

Qualifying specialties include neurology, immunology, rheumatology, endocrinology, nephrology, or hepatology, or another provider with experience treating IgG4-RD.

Denial Risk

Clinical Eligibility and Safety Requirements

Before treatment, confirm safety eligibility and document the required infection screening and concomitant-therapy review. Uplizna should not be used with specified immunosuppressive, complement-inhibitor, or anti-CD20 therapies.

The prescriber must attest that the member has no active or latent untreated infection, including clinically important localized infection, hepatitis B, or tuberculosis, consistent with the FDA label.
The member must not be receiving other immunosuppressant-type drugs, including alemtuzumab, natalizumab, cyclosporine, methotrexate, mitoxantrone, cyclophosphamide, or tocilizumab.
Maintenance corticosteroids are also restricted, except premedication, rescue therapy, or doses of 20 mg/day or less.
For NMOSD, do not combine Uplizna with complement inhibitors such as eculizumab or ravulizumab, or anti-CD20-directed antibodies such as rituximab.
For IgG4-RD, do not combine Uplizna with anti-CD20-directed antibodies such as rituximab.

Step Therapy

Required Prior Treatment for gMG

For gMG, document an inadequate treatment response, serious side effects, or contraindication to both pyridostigmine and formulary glucocorticoids before Uplizna is approved.

The required inadequate-response trial period is 2 weeks.
Include the medication names, dates and duration of therapy, response, adverse effects, or clinical contraindication for each prerequisite therapy.

Unsupported block type: denial_riskиђ},{

Denial Risk

Contraindications

Do not administer Uplizna when a listed contraindication is present.

Previous life-threatening infusion reaction to Uplizna
Active hepatitis B infection
Active or untreated latent tuberculosis

Denial Risk

Experimental or Investigational Use

Uses of Uplizna outside the recognized policy indications are considered experimental or investigational and are handled under the applicable off-label policy.

Submit clinical rationale and supporting documentation for any exception request.
Coverage is not established for uses outside NMOSD, IgG4-RD, and gMG criteria.

Failure to achieve an adequate decrease in serum IgG4 concentrations with glucocorticoid alone

Glucocorticoid dependenceInability to reduce the glucocorticoid dose to less than 5 mg/day without a disease flare or worsening symptoms

2019 ACR/EULAR IgG4-RD classification criteria

Entry criteriaCharacteristic clinical or radiologic involvement of a typical organ, or pathologic evidence of an inflammatory process with a lymphoplasmacytic infiltrate of uncertain etiology in a typical organ

Exclusion criteriaNo exclusion criteria may be present after the entry criteria are met

Inclusion scoreThe total inclusion score must be at least 20 points

Neuromyelitis optica spectrum disorder (NMOSD)

Disease typeA rare, relapsing autoimmune disorder

Affected systemThe disorder affects the brain and spinal cord

Predominant manifestationsOptic neuritis and/or myelitis are the predominant clinical characteristics

Immunoglobulin G4-related disease (IgG4-RD)

Disease typeAn immune-mediated condition

Organ effectsIt causes swelling or masses in various organs, along with specific tissue inflammation and scarring

Diagnostic basisDiagnosis incorporates clinical presentation, serum IgG4 levels, and characteristic histopathology

Myasthenia gravis (MG)

Disease typeA rare autoimmune disorder

Mechanism and symptomsAntibodies block neuromuscular transmission, causing fatigable skeletal-muscle weakness that improves after rest

Generalized formGeneralized myasthenia gravis affects muscles throughout the body, unlike ocular myasthenia gravis, which affects the eye and eyelid muscles

Baseline EDSS, relapse rate, and visual acuity are documented; baseline EDSS is ≤8.

No active or latent untreated infection and no prohibited concomitant immunosuppressive, complement-inhibitor, or anti-CD20-directed antibody therapy.

IgG4-RD

Documented IgG4-RD affecting at least 2 organs or sites.
Baseline disease activity and treatment goals are documented.
There is an inadequate response or contraindication to glucocorticoid therapy.
No active or latent untreated infection and no prohibited concomitant immunosuppressive or anti-CD20-directed antibody therapy.

Generalized myasthenia gravis

Documented generalized myasthenia gravis with MGFA class II, III, or IV and positive AChR or MuSK antibody testing.
An MG-ADL score or another efficacy-monitoring measure is documented.
There is no active or latent untreated infection.
There is an inadequate response, serious side effects, or contraindication to a 2-week trial of pyridostigmine and formulary glucocorticoids.
Uplizna will not be used concurrently with the prohibited gMG therapies listed in the policy.

For IgG4-RD, therapy has produced a positive clinical response, demonstrated by decreased frequency or severity of flares and/or improvement in signs and symptoms.

For generalized myasthenia gravis, therapy has produced low disease activity or clinical improvement, demonstrated by improved MG-ADL score, reduced signs and symptoms, or stabilization, reduction, or discontinuation of baseline immunosuppressive therapy.

There is no evidence of intolerable adverse effects or drug toxicity where applicable, including serious infusion reactions or serious systemic infections.

The prescriber attests to ongoing monitoring for infection, including tuberculosis and hepatitis B reactivation, according to the FDA label.