Medical Pharmacologic Treatment of Multiple Sclerosis
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Defines medical necessity, site-of-service review, and coverage criteria for specified IV and injectable disease-modifying therapies for multiple sclerosis for Premera Bluecross members; applies to providers requesting medical-benefit coverage and prior authorization for listed MS drugs.
Updated criteria for Ocrevus (ocrelizumab) adding coverage for the treatment of pediatric individuals with relapsing-remitting multiple sclerosis.
Removed reference to non-formulary exceptions reviews.
Added prescriber requirement and age requirement to Briumvi, Lemtrada, Tysabri, Tyruko, and Ocrevus.
Added a prescriptive exception for site-of-service requirements for certain individuals receiving treatment for cytokine release syndrome (CRS).
Clarified that the medications listed in this policy are subject to the product's FDA dosage and administration prescribing information.
Coverage Criteria and Site-of-Service Rules
Site-of-Service and Drug-Specific Medical Necessity
Considered medically necessary when ALL of the following drug- and patient-specific conditions are met (drug-specific variations noted):
General SOS and drug requirements
- Age: Individual is aged 18 years or older for most agents (exceptions: site-of-service reviews apply to age >= 13; Ocrevus pediatric relapsing use: age >= 10 years and weight >= 25 kg).age limits specified per agent
- EDSS: Agent-specific EDSS thresholds: typically EDSS < 6 for relapsing indications; Ocrevus and Ocrevus Zunovo for primary progressive disease require EDSS < 7.EDSS thresholds vary by agent
Children and dosing per FDA labeling.
TOUCH registry required for Tysabri; Tyruko requires REMS enrollment.
Hospital-based outpatient setting medical necessity
Hospital-based outpatient infusion is considered medically necessary for the initial course or re-initiation in specific circumstances when ALL of the following apply:
Hospital-based outpatient only when these high-risk criteria present.
General coverage conditions
Covered when medical-benefit and product-specific FDA prescribing information and any policy-specific prescriber/age requirements are met.
See prior authorization requirements and coding updates.
Age limits are determined according to FDA-approved indications.
Reference to non-formulary exception reviews has been removed.
All uses of the medications listed in this policy must follow the product's US Food and Drug Administration (FDA) dosage and administration prescribing information. All other uses that are not consistent with the FDA dosing and administration instructions are considered investigational and are not covered under this policy.
References to non-formulary exception reviews have been removed from this policy and are no longer applicable. The policy history documents this removal and notes that prior non-formulary exception language was deleted during the most recent updates.
Hospital-based outpatient infusion and injection sites are considered not medically necessary for administration of infusion or injectable therapies when the site-of-service criteria in this policy are not met. Examples of high-risk clinical criteria that may justify hospital-based outpatient care are specified (e.g., hypotension requiring vasopressors; hypoxia requiring high-flow oxygen or positive pressure ventilation) and, absent those or the other site-of-service criteria, the hospital-based outpatient site is not an appropriate or covered setting for these services.
Site-of-service medical necessity review does not apply to pediatric individuals under age 13 years. The policy limits SOS review to individuals aged 13 and older because pediatric patients have distinct physiologic and care needs that affect infusion administration. Exceptions and statutory considerations (for example, references to Alaska fully insured members) are described elsewhere in the policy history and notes.
HCPCS/Coding and Age/EDSS Key Values
| Q5134 | Injection, natalizumab-sztn, biosimilar (Tyruko), 1 mg |
| J2351 | new HCPCS code added (document references coding update) |
Provider Requirements, Prior Authorization, and Documentation
Pre-authorization and coding required for listed IV/injectable MS therapies
Specific IV and injectable disease-modifying therapies listed in this policy (Briumvi, Ocrevus, Ocrevus Zunovo, Tyruko, Tysabri, and Lemtrada) are subject to medical‑benefit review and site‑of‑service review; use the HCPCS codes listed in the policy (J0202, J2323, J2329, J2350, J2351, Q5134) for authorization and billing.
Medical‑benefit requests require prior authorization (coding updated)
Medications in this policy are managed under the medical benefit and require prior authorization; coding updates include the addition of HCPCS code J2351 (ocrelizumab + hyaluronidase).
- Medications listed are subject to the medical benefit and prior authorization.
- Coding update: new HCPCS code J2351 added for Ocrevus Zunovo.
Step requirement: Lemtrada (alemtuzumab) — two prior DMD failures required
Alemtuzumab (Lemtrada) will only be considered when the patient is aged 17 years or older and has had an inadequate response to two or more disease‑modifying drugs indicated for MS; Lemtrada must not be used concurrently with other MS DMDs and should be prescribed by or in consultation with a neurologist or MS specialist.
- Age requirement: patient aged ≥17 years for Lemtrada.
- Step requirement: inadequate response to ≥2 MS disease‑modifying drugs (listed in policy).
- Must not be used concurrently with other MS DMDs; prescribed by or in consultation with a neurologist/MS specialist.
Document prescriber specialty, REMS/registry enrollment, and any policy exceptions
Ensure site‑of‑service requests and prescribing meet any additional policy exceptions (e.g., exceptions noted for cytokine release syndrome) and that prescriber specialty and enrollment requirements (TOUCH/Tyruko REMS) are documented when applicable.
- Document enrollment in TOUCH registry for Tysabri or Tyruko REMS program when applicable.
- Note policy exceptions (e.g., CRS) and Alaska-specific site‑of‑service guidance in history; include supporting documentation.
Required medical record documentation for prior authorization
Submit the patient’s medical records that document the office visit (diagnosis, relevant history, physical exam) and complete medication history to demonstrate that medical necessity and any step or site‑of‑service criteria are met.
- Include office visit notes with diagnosis, relevant history, physical evaluation, and medication history.
- Documentation should support age, EDSS, prior‑therapy failures, and prescriber specialty when applicable.
Prescribing and dosing must match FDA labeling; observe product‑specific prescriber/age requirements
Prescriptions, dosing, and administration must follow the product’s FDA‑approved prescribing information; prescriber and age requirements appended to specific products (Briumvi, Lemtrada, Tysabri, Tyruko, Ocrevus) must be met.
- Follow FDA dosage and administration for each product.
- Ensure prescriber and age requirements in policy (e.g., pediatric Ocrevus, Lemtrada age ≥17) are met before authorization.
Site‑of‑service denial risk for hospital/outpatient infusion requests
Requests for infusion or hospital‑based outpatient administration will be considered not medically necessary when the policy’s site‑of‑service criteria are not met; ensure site‑of‑service criteria are documented to avoid denial.
- Hospital‑based outpatient settings are only medically necessary when site‑of‑service clinical, time‑based, or geographic/access criteria in the policy are satisfied.
- If site‑of‑service criteria are not met, infusion/hospital outpatient requests may be denied as not medically necessary.
Age threshold for site‑of‑service review (>=13 years) — pediatric exception may affect approvals
Site‑of‑service medical necessity review applies only to individuals aged 13 years and older; requests for pediatric site‑of‑service review for younger individuals may be excluded from site‑of‑service review and could be denied under this policy’s age criterion.
- Site‑of‑service review age threshold: ≥13 years.
- Pediatric individuals under age 13 are excluded from the site‑of‑service medical necessity review per policy.
Key Terms and Definitions
Clinical Background
Multiple sclerosis (MS) is an immune-mediated disease that causes damage to nerves in the brain and spinal cord and results in variable clinical presentations and disability. This policy addresses the medical-benefit management and site-of-service considerations for IV and injectable disease-modifying therapies used to treat MS, specifying patient age and disability thresholds, prescriber requirements, and setting-specific medical necessity for infusion and injection administration.
Revision History and Policy Changes
Updated criteria to add coverage for Ocrevus (ocrelizumab) for pediatric individuals with relapsing-remitting multiple sclerosis.
Site-of-service review was added for Ocrevus Zunovo (ocrelizumab-hyaluronidase-ocsq) and the Site of Service Medical Necessity criteria were clarified to apply to injection drugs following a 90-day provider notification.
Interim review approved June 10, 2025: moved Zunovo, Tyruko, and Tysabri from Policy 5.01.565 into this policy; added prescriber and age requirements for Briumvi, Lemtrada, Tysabri, Tyruko, and Ocrevus; added CRS site-of-service exception; added HCPCS code J2351.
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