Natalizumab — CPB 0751 | AETNA Coverage Update

Aetna modified CPB 0751 for natalizumab (Tysabri and biosimilar Tyruko), effective December 3, 2025. Here's what billing teams need to do.

Aetna, a CVS Health company, updated its natalizumab coverage policy under CPB 0751 Aetna system, covering HCPCS codes J2323 (natalizumab) and Q5134 (natalizumab-sztn biosimilar) for commercial medical plans. The policy governs coverage for relapsing forms of multiple sclerosis, clinically isolated syndrome, and Crohn's disease — and the criteria for each are tighter than they look. If your practice bills infusion services under CPT 96365–96368 for either of these products, review your prior authorization workflow before December 3, 2025.

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Quick-Reference Table

Field	Detail Copy
Payer	Aetna
Policy	Natalizumab – CPB 0751
Policy Code	CPB 0751
Change Type	Modified
Effective Date	December 3, 2025
Impact Level	High
Specialties Affected	Neurology, Gastroenterology, Infusion/Specialty Pharmacy
Key Action	Confirm anti-JCV antibody testing (CPT 86711) is documented before submitting precertification for any natalizumab claim

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Aetna Natalizumab Coverage Criteria and Medical Necessity Requirements 2025

The Aetna natalizumab coverage policy requires precertification for every claim. Call (866) 752-7021 or fax (888) 267-3277. This is not optional — it applies to all Aetna participating providers and members in applicable plan designs.

Medical necessity hinges on three things: the right prescriber specialty, confirmed anti-JCV antibody testing, and the right diagnosis. Get any one of those wrong and you're looking at a claim denial before you ever get to clinical review.

Prescriber Specialty Requirements

Aetna won't approve natalizumab unless the prescribing physician matches the indication. For Crohn's disease (ICD-10 K50.00–K50.919), the prescriber must be a gastroenterologist. For relapsing forms of MS (ICD-10 G35) and clinically isolated syndrome (G37.81, G37.89), the prescriber must be a neurologist. "In consultation with" is acceptable — but that relationship needs to be documented in the record.

Initial Approval: What Aetna Requires

For Crohn's disease, the member must be an adult who has already received at least one other biologic indicated for moderately to severely active CD. This is a step therapy requirement. Natalizumab billing for a Crohn's patient who hasn't tried a prior biologic — adalimumab, infliximab, or a biosimilar equivalent — will not meet medical necessity under this policy. The relevant prior biologics include HCPCS codes like J0139 (adalimumab), J1745 (infliximab), and multiple adalimumab biosimilars (Q5140–Q5145).

For relapsing forms of MS (relapsing-remitting and secondary progressive MS with ongoing relapse), the member must have a confirmed diagnosis under ICD-10 G35 and documented anti-JCV antibody testing. Same testing requirement applies to clinically isolated syndrome under G37.81 and G37.89.

Anti-JCV antibody testing is captured under CPT 86711. This code must be in the record before precertification goes in. Aetna also references CPT 86790 for ELISA-based anti-JCV antibody testing. Either way — no JCV test, no approval.

Continuation of Therapy

Continuation criteria differ by indication. For MS and CIS, Aetna looks for disease stability or improvement while on the drug. The bar is relatively straightforward.

For Crohn's disease, continuation requires either remission or a positive clinical response. That response can come from improvement in any one of the following: abdominal pain or tenderness, diarrhea, body weight, abdominal mass, hematocrit, mucosal appearance on endoscopy or imaging (computed tomography enterography, magnetic resonance enterography, or intestinal ultrasound), or improvement on a validated scoring tool like the Crohn's Disease Activity Index (CDAI). The "any of the following" language is important — your gastroenterologist doesn't need to show improvement across all parameters, just one. Make sure the clinical notes document at least one of these markers clearly.

Site of Care Requirements

Aetna's Site of Care Utilization Management Policy applies to natalizumab infusions on commercial plans. This affects where CPT 96365–96368 infusion codes get billed. If your infusion site isn't compliant with Aetna's site-of-care policy, expect reimbursement problems regardless of whether medical necessity criteria are met. Check the Utilization Management Policy on Site of Care for Specialty Drug Infusions before scheduling infusion appointments for new patients.

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Aetna Natalizumab Exclusions and Non-Covered Indications

Aetna considers all indications not listed in the policy experimental, investigational, or unproven. That's a broad exclusion. Only three indications qualify for coverage: relapsing forms of MS (including relapsing-remitting and secondary progressive MS with active relapse), clinically isolated syndrome, and moderately to severely active Crohn's disease in adults who have tried a prior biologic.

Off-label use — including chronic progressive MS without relapse, neuromyelitis optica (G36.0), Rasmussen encephalitis (G04.81), or ulcerative colitis (K51.00–K51.319) — will not meet medical necessity under this policy. The code list includes these ICD-10 codes, but their presence in the document reflects related policy context, not covered indications for natalizumab. Don't assume a code appearing in a policy table means Aetna covers that use.

CPT codes 87798 and 87801 — nucleic acid detection tests used as biomarkers for predicting PML risk — are referenced in the policy but fall outside the standard covered category. Their role is limited to experimental PML risk stratification contexts. Don't build these into a routine natalizumab billing workflow.

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Coverage Indications at a Glance

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Aetna Natalizumab Billing Guidelines and Action Items 2025

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If you serve a mixed neurological or GI payer mix and aren't sure how this coverage policy interacts with your specific plan types, talk to your compliance officer before the December 3, 2025 effective date.

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CPT, HCPCS, and ICD-10 Codes for Natalizumab Under CPB 0751

Covered HCPCS Codes (When Selection Criteria Are Met)

Code	Type	Description Copy
J2323	HCPCS	Injection, natalizumab, 1 mg
Q5134	HCPCS	Injection, natalizumab-sztn (Tyruko), biosimilar, 1 mg

Covered CPT Codes (When Selection Criteria Are Met)

Code	Type	Description Copy
86711	CPT	Antibody; JC (John Cunningham) virus

Key ICD-10-CM Diagnosis Codes

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