Neighborhood Health Plan RI natalizumab Prior Auth

Coverage and Medical Necessity Criteria

Initial Approval General Criteria (applies to indications)

Covered when ALL of the following are met for initial approval:

Age and enrollment: Patient is at least 18 years of age; prescriber and patient are enrolled in and meet the conditions of the TOUCH (or applicable REMS) program.age >= 18

TOUCH/REMS enrollment required

JCV testing: Documented negative anti‑JCV antibody ELISA test within the past 6 months.negative within 6 months

Presence of anti‑JCV antibodies will prompt case‑by‑case review

Concomitant therapy: Not used in combination with antineoplastic, immunosuppressant, or other immunomodulating agents; used as single‑agent therapy.single agent

Concurrent biologics or immunosuppressants are not permitted

Immune status: Patient must not have a systemic medical condition resulting in significantly compromised immune system function.

Medicare step therapy exception: Medicare members with prior receipt of this medication within the past 365 days are not subject to step therapy requirements.

Multiple Sclerosis — Initial Therapy

MS-specific initial coverage (ALL must be met):

Diagnosis of a relapsing form of multiple sclerosis (relapsing‑remitting MS, active secondary progressive MS, or clinically isolated syndrome).diagnostic criteria met

Definitive RRMS diagnosis typically requires dissemination in time and space often supported by MRI

Specialty prescriber: Prescribed by or in consultation with a neurologist; confirmed diagnosis documented (e.g., MRI).neurology involvement

Therapy setting: Used as single‑agent therapy for MS with ongoing monitoring per renewal criteria.single agent and monitored

Monitoring includes clinical measures and MRI

Crohn's Disease — Initial Therapy and Renewal Conditions

Crohn's disease-specific initial coverage and renewal:

Disease severity: Moderate to severe active Crohn's disease; baseline disease severity must be assessed using an objective measure or tool.moderate to severe

Objective tools include Harvey‑Bradshaw Index, biomarkers, endoscopy

Prior biologic therapy: Documented failure, intolerance, or contraindication to infliximab IV or adalimumab for at least 3 months at maximum tolerated doses; AND failure, intolerance, or contraindication to ustekinumab for at least 6 months at maximum tolerated doses.documented failure/intolerance/contraindication

Prior biologic therapy required before natalizumab

Specialty prescriber: Prescribed by or in consultation with a gastroenterologist; used as single‑agent therapy and not concurrently with other biologic targeted synthetic therapies or immunosuppressants for Crohn's disease.

Renewal Criteria (MS and Crohn's)

Renewal criteria (coverage can be renewed when ALL of the following are met):

Continued criteria: Patient continues to meet the universal and indication‑specific criteria identified for initial approval.ongoing compliance

Tolerability: Absence of unacceptable toxicity from natalizumab (examples: hypersensitivity/antibody formation, hepatotoxicity, signs or symptoms of PML, severe infections, thrombocytopenia).no unacceptable toxicity

Therapy should be discontinued for persistent neutralizing antibodies

MS response monitoring: For MS: continuous monitoring demonstrates clinical benefit such as decreased annualized relapse rate, no new/worsening MRI lesions, or no progression on disability measures (EDSS, T25‑FW, 9‑HPT).evidence of benefit

Subsequent Renewal Criteria (Crohn's disease)

Covered when ALL of the following are met for subsequent renewals:

Renewal requirements: 1) Patient does not require additional corticosteroid use that exceeds 3 months in a calendar year to control Crohn's disease; AND 2) Documented disease response compared with baseline evidenced by improvement in signs and symptoms (for example: endoscopic activity, number of liquid stools, abdominal pain severity, abdominal mass, body weight regain, hematocrit, extra‑intestinal complications), tapering or discontinuation of corticosteroid therapy, use of anti‑diarrheal drugs, improved biomarkers (fecal calprotectin or CRP), and/or improvement on a disease activity score (e.g., Harvey‑Bradshaw Index).steroid use <= 3 months/year

Applies to all subsequent renewals for Crohn's disease

Dosage and Administration

Administration requirement:

Dose schedule: Administer 300 mg intravenously over one hour every four weeks.300 mg IV q4w

Concurrent use of natalizumab for Crohn's disease with other biologic targeted synthetic therapies or with systemic immunosuppressants is excluded. The policy requires that Tysabri be used as single‑agent therapy for Crohn's disease and explicitly disallows concurrent treatment with other biologics (for example, upadacitinib) or immunosuppressants (for example, 6‑mercaptopurine, azathioprine, cyclosporine, methotrexate).

Providers should document prior biologic therapy failures, intolerances, or contraindications per the Crohn's criteria, but must not combine natalizumab with other agents listed above when requesting coverage.

For Medicare members, the coverage criteria in this document apply only when there are no applicable CMS National Coverage Determinations (NCDs) or Local Coverage Determinations (LCDs). Where an NCD or LCD exists, that determination governs and must be followed for Medicare Part B claims.

Providers should consult the Medicare coverage resources or the applicable MAC LCD/NCD to confirm whether Medicare-specific guidance supersedes these plan criteria prior to submission.

Use of natalizumab in combination with antineoplastic agents, systemic immunosuppressants, or other immunomodulating therapies is considered not medically necessary under this policy. The universal criteria state that natalizumab must not be used in combination with antineoplastic, immunosuppressant, or immunomodulating agents, and requests that indicate concurrent use with such agents will be subject to denial.

The plan's criteria are intended to ensure use of natalizumab is consistent with FDA labeling and relevant clinical literature, to confirm therapy is for medically accepted indications, to minimize risk of adverse effects, and to prefer more cost‑effective options when appropriate. Individual consideration will be given to each request based on submitted clinical information.

Billing, Codes, and Limits

Dosing and billingmixedCovered

HCPCS unit	300 billable units every 28 days (per policy max units)
Natalizumab 300 mg IV	Dose: 300 mg IV over one hour every 4 weeks

Administration detailsmixedCovered

300 mg IV

Administer 300 mg intravenously over one hour every four weeks

Covered HCPCS CodesHCPCSCovered

J2323

Injection, natalizumab, 1 mg; 1 billable unit = J2323

NDCsNDC

64406-0008-xX

Tysabri 300 mL single-dose vial: 64406-0008-xX

Covered ICD-10 CodesICD-10Covered

G35	Multiple Sclerosis
K50.00	Crohn's disease of small intestine without complications
K50.011	Crohn's disease of small intestine with rectal bleeding
K50.012	Crohn's disease of small intestine with intestinal obstruction
K50.013	Crohn's disease of small intestine with fistula
K50.014	Crohn's disease of small intestine with abscess
K50.018	Crohn's disease of small intestine with other complication
K50.019	Crohn's disease of small intestine with unspecified complications
K50.10	Crohn's disease of large intestine without complications
K50.111	Crohn's disease of large intestine with rectal bleeding

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Maximum HCPCS billing

Maximum HCPCS billing300 billable units every 28 days

Billing unit codeHCPCS billing reported as 1 mg units (J2323) — aggregate capped at 300 units/28 days per policy

Billing intervalLimit applies per 28-day period (monthly cycle used by policy)

Steroid exposure limit

Renewal implicationExceeding 3 months/year of steroid dependence may lead to denial of subsequent renewal requests

Assessment periodSteroid use measured across a calendar year for subsequent renewals

Prior Authorization, Documentation, and Denial Risks

Prior Authorization

Prior Authorization Requirements

Prior authorization is required. Requests must meet age, program enrollment, testing, prescriber specialty, and prior-therapy conditions before approval.

Medicare members who previously received the medication within the past 365 days are exempt from step therapy requirements.
Not authorized for use in combination with other biologic targeted synthetic therapies or concomitant immunosuppressants/antineoplastics.

Billing Rule

Prior Authorization and Dosing

Prior authorization and dosing specifics. Authorization should reflect the FDA‑specified dose and applicable billing codes.

Background and Indications

Natalizumab (Tysabri) is an integrin receptor antagonist approved for relapsing forms of multiple sclerosis and for moderate to severe Crohn's disease. It has demonstrated reductions in MS relapse rate and disease progression in clinical trials but carries a boxed warning for progressive multifocal leukoencephalopathy (PML); recognized risk factors for PML include the presence of anti‑JCV antibodies, prior immunosuppressant therapy, and longer duration of natalizumab exposure.

Because of the PML risk, the policy requires enrollment in the TOUCH/REMS program and recent negative anti‑JCV antibody testing as part of authorization. Prescribers and patients must be counseled about PML risk and monitored according to REMS and clinical guidance.

Key Definitions and Risk Factors

PML risk factors

Anti‑JCV antibody statusPresence of anti‑JCV antibodies increases PML risk; JCV positivity will be reviewed case‑by‑case

Anti‑JCV index thresholdsElevated anti‑JCV antibody index (e.g., index >0.9) is associated with higher PML risk

Prior immunosuppressant exposurePrior treatment with immunosuppressants (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate) increases PML risk

Treatment durationLonger natalizumab exposure, especially beyond 2 years, increases PML risk

Clinically isolated syndrome (CIS) definition

CIS definitionA monophasic clinical episode with patient-reported symptoms and objective focal or multifocal inflammatory demyelinating findings in the CNS, absence of fever/infection, neurologic symptom duration ≥24 hours, and patient not known to have multiple sclerosis

OpenPayer

Tysabri (Natalizumab) intravenous therapy coverage criteria

Coverage and Medical Necessity Criteria

Billing, Codes, and Limits

Prior Authorization, Documentation, and Denial Risks

Background and Indications

Key Definitions and Risk Factors