CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Tysabri (Natalizumab)

Coverage, clinical criteria, dosing, renewal rules, and billing codes for natalizumab (Tysabri) for Multiple Sclerosis and Crohn's Disease for Neighborhood Health Plan of Rhode Island (Medicaid, Commercial, Medicare).

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyTysabri (Natalizumab)

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 1, 2020

Next Review Date

Key ActionPrescriber and patient must be enrolled in and meet TOUCH (Tysabri) or REMS (Tyruko) program conditions; document negative JCV antibody ELISA within past 6 months; include confirmatory diagnostic documentation and specialty consultation notes as required.

POLICY UPDATE CHANGES

No material clinical or coverage changes noted in this update.

2Covered Indications

300Max billed units

>=18Minimum age (years)

Coverage Summary

Coverage stance: covered_with_criteria for natalizumab (Tysabri) when used for approved indications of relapsing forms of multiple sclerosis and for moderate‑to‑severe Crohn's disease, consistent with the policy scope and clinical criteria. Scope covers Medicaid, Commercial, and Medicare populations. (See scope summary.)

Key thresholds

Age>= 18 years

JCV antibody test recencyDocumented negative JCV antibody ELISA within the past 6 months

Dose300 mg IV every 4 weeks (administer IV over one hour)

Max units300 billable units every 28 days

MS renewal response definition>= 1 relapse OR >= 2 new MRI-detected lesions OR increased disability over a one-year period

Crohn prior biologic failure durationsInfliximab/adalimumab failure >= 3 months; ustekinumab failure >= 6 months (at maximum tolerated doses)

Initial Therapy Criteria

Initial Approval Criteria

Covered when ALL of the following are met:

ALL of the following

Universal Criteria
- Patient is at least 18 years of age
- Prescriber and patient must be enrolled in and meet the conditions of the TOUCH (applicable to Tysabri) or REMS (applicable to Tyruko) programs
- Documented negative JCV antibody ELISA test within the past 6 monthsnegative within past 6 months
- Not used in combination with antineoplastic, immunosuppressant, or immunomodulating agents
- Patient must not have a systemic medical condition resulting in significantly compromised immune system function
- Medicare members who have previously received this medication within the past 365 days are not subject to Step Therapy Requirements
Indication (ONE of)
- Multiple Sclerosis (MS)
  - Patient has a diagnosis of a relapsing form of multiple sclerosis (relapsing‑remitting MS, active secondary progressive MS, or clinically isolated syndrome)
  - Must be prescribed by or in consultation with a neurologist
  - Patient must have a confirmed diagnosis of MS as documented by laboratory report (i.e. MRI)
  - Used as single agent therapy
- Crohn's Disease (CD)
  - Patient has moderate to severe active Crohn's disease

Continuation / Renewal Criteria

Renewal Criteria

Coverage renewal requires ALL of the following:

ALL of the following

Patient continues to meet the universal and other indication-specific relevant criteria identified in Initial Approval Criteria
Absence of unacceptable toxicity from the drug (examples include hypersensitivity/antibody formation, hepatotoxicity, signs or symptoms of PML, herpes infections including encephalitis/meningitis, immunosuppression, various infections, thrombocytopenia, etc.)
Indication-specific renewal
- Multiple Sclerosis (MS)
  - Continuous monitoring of response to therapy indicates a beneficial response
  - Inadequate response (after sufficient time and adherence) is defined as ≥ 1 relapse, ≥ 2 unequivocally new MRI-detected lesions, or increased disability on examination over a one-year period (and would indicate lack of benefit)>= 1 relapse OR >= 2 new MRI lesions OR increased disability over 1 year
  - Therapy should be discontinued in patients who have persistent neutralizing antibodies to natalizumab
- Crohn's Disease (CD)
  - Initial renewal only: Clinical response and remission of disease is seen by 12 weeksby 12 weeks
  - Second renewal only: Patient has been tapered off of oral corticosteroids within 6 months of starting natalizumab; AND disease response as indicated by improvement in signs and symptoms compared to baseline (examples: endoscopic activity, number of liquid stools, abdominal pain, abdominal mass, body weight regain, hematocrit, extraintestinal complications, tapering/discontinuation of corticosteroids, anti-diarrheal use, improvement in biomarkers such as fecal calprotectin or CRP, improvement on disease activity scoring tool)tapered off steroids within 6 months
  - All subsequent renewals: Patient does not require additional steroid use that exceeds 3 months in a calendar year to control their Crohn's disease; AND disease response as indicated by improvement in signs and symptoms compared to baseline (same examples as above)<= 3 months steroid use per calendar year

Unproven Uses and Exclusions

Exclusions/contraindications and safety cautions include: do not use natalizumab concurrently with antineoplastic, immunosuppressant, or immunomodulating agents; avoid use in patients with systemic medical conditions resulting in significantly compromised immune function; and therapy should be discontinued for patients with persistent neutralizing antibodies to natalizumab.

Major safety concerns emphasized in the policy include risk of progressive multifocal leukoencephalopathy (PML) and other serious infections; the policy lists unacceptable toxicities such as signs or symptoms of PML, herpes encephalitis/meningitis, severe infections, hepatotoxicity, thrombocytopenia, and hypersensitivity/antibody formation.

Applicable Codes

HCPCS (billing unit)HCPCSCovered

J2323

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

NDC(s)NDCCovered

64406-0008-xx

Tysabri 300 mg/15 mL single-dose vial

Covered ICD-10 diagnosis 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

1–10 of 29

1/3

mixed

No codes listed

Provider Actions & Billing

Prior Authorization

Enrollment in TOUCH/REMS and documentation

Prescriber and patient must be enrolled in and meet the conditions of the TOUCH (Tysabri) or REMS (Tyruko) programs; document a negative JCV antibody ELISA test within the past 6 months; include confirmatory diagnostic documentation (e.g., MRI for MS) and specialty consultation notes as required.

Enrollment in TOUCH (Tysabri) or REMS (Tyruko) program
Documented negative JCV antibody ELISA within past 6 months
Confirmatory diagnostic documentation (e.g., MRI for MS) and specialty consultation notes

Documentation Required

Specialist prescription requirement

Tysabri must be prescribed by or in consultation with a neurologist for multiple sclerosis and by or in consultation with a gastroenterologist for Crohn's disease; baseline disease severity assessment must be documented for Crohn's disease.

Neurologist involvement for MS prescriptions
Gastroenterologist involvement for Crohn's prescriptions
Document baseline disease severity assessment for Crohn's

Billing Rule

HCPCS unit billing

Report J2323 units consistent with a 300 mg dose (J2323 = injection, natalizumab, 1 mg; 1 billable unit = 1 mg). The plan specifies a maximum of 300 billable units every 28 days.

Use HCPCS code J2323
1 billable unit = 1 mg
300 units per 28 days = 300 mg dose

Denial Risk

Concurrent immunosuppressant/biologic use

Claims may be denied or not approved if natalizumab is used concurrently with antineoplastic, immunosuppressant, immunomodulating agents, or other biologic/targeted therapies for Crohn's disease.

Concurrent use with antineoplastic, immunosuppressant, or immunomodulating agents may lead to denial
Concurrent use with another biologic or targeted therapy for Crohn's may lead to denial

Documentation Required

Evidence of prior biologic therapy for Crohn's

Provide documentation of failure, intolerance, or contraindication to infliximab or adalimumab for at least 3 months at maximum tolerated doses and to ustekinumab for at least 6 months at maximum tolerated doses for Crohn's disease prior to approval.

Infliximab or adalimumab failure/intolerance/contraindication ≥ 3 months at max tolerated doses
Ustekinumab failure/intolerance/contraindication ≥ 6 months at max tolerated doses

Clinical Evidence

68%AFFIRM trial - annualized relapse rate reduction vs placebo

42%SENTINEL trial - risk reduction of disability progression vs placebo

300Max billed units (billable mg) per 28 days

>=18Minimum age for coverage (years)

Background: Natalizumab is an integrin receptor antagonist with demonstrated efficacy in major trials (AFFIRM and SENTINEL in MS; ENACT/ENACT-2 in Crohn's disease) that showed substantial reductions in relapse rate and disability progression in relapsing MS (AFFIRM: 68% reduction in ARR; SENTINEL: 42% reduction in risk of disability progression), and benefit in Crohn's trials. The recommended dose is 300 mg IV every 4 weeks.

Major safety concerns include the black box risk of progressive multifocal leukoencephalopathy (PML) and other serious infections; risk factors and quantified PML risk estimates are described in the policy. Use requires enrollment in the TOUCH/REMS program to monitor and mitigate PML risk.

Background

Natalizumab mechanism and approvals: Natalizumab (Tysabri) is an integrin receptor antagonist FDA‑approved for relapsing forms of multiple sclerosis and for Crohn's disease. Clinical trials referenced in the policy include AFFIRM and SENTINEL for MS and ENACT (and ENACT-2) for Crohn's disease.

Major risks and monitoring: The policy highlights a black box warning for progressive multifocal leukoencephalopathy (PML) and other serious infections, lists risk factors for PML (including anti‑JCV antibody presence, prior immunosuppressant use, and longer treatment duration with graded risk estimates), and requires prescriber and patient enrollment in the TOUCH (Tysabri) or REMS program with documentation of a documented negative JCV antibody ELISA within the past 6 months prior to use.

Dosing and billing: Dose is specified as 300 mg IV over one hour every 4 weeks, with HCPCS billing code J2323 (1 mg per billable unit) and product NDC 64406-0008-xx.

Definitions

Active secondary progressive MS (SPMS)EDSS score >= 3.0; disease progressive >= 3 months after initial relapsing‑remitting course AND either >= 1 relapse in prior 2 years OR gadolinium‑enhancing/new/enlarging T2 lesions on MRI

Clinically isolated syndrome (CIS)A monophasic focal inflammatory demyelinating event with neurologic symptoms >=24 hours, absence of fever/infection, and patient not known to have MS