Is continuation of Tysabri (Natalizumab) 300mg IV q6w medically necessary for a patient with multiple sclerosis (MS) and a negative JCV (John Cunningham Virus) status, given stable MRI scans and disease stability?

Medical Necessity Determination for Natalizumab (Tysabri) Continuation

Yes, continuation of Tysabri 300mg IV every 6 weeks is medically necessary for this patient with relapsing-remitting multiple sclerosis who demonstrates disease stability with negative JCV antibody status, stable MRI findings, and documented clinical improvement on therapy.

Rationale for Medical Necessity

This patient meets established criteria for continuation of natalizumab therapy based on multiple factors:

Disease Stability and Treatment Response

• The patient demonstrates clear disease stability with stable MRI findings showing no new lesions or disease progression, which satisfies the Aetna continuation criteria requiring "disease stability or improvement" 1
• The American Academy of Neurology recommends that patients clinically stable on natalizumab should continue therapy, as discontinuation can lead to disease reactivation or rebound, increasing morbidity 1
• The patient's EDSS score of 2.0 and stable neurological examinations document maintained functional status, supporting continued treatment efficacy 1

Prior Treatment Failures Justify Continued Use

• This patient has documented failure of alternative disease-modifying therapies (Avonex discontinued due to new lesions; Ocrevus discontinued due to intolerable side effects), establishing natalizumab as medically necessary when first-line agents proved inadequate 1
• The patient successfully resumed Tysabri after Ocrevus failure and has maintained stability since, demonstrating this is the most effective tolerated therapy for this individual 1

Low PML Risk Profile Supports Continuation

• The patient's JCV antibody-negative status places her at significantly lower PML risk (approximately 1 in 10,000) compared to JCV-positive patients 2, 3
• The FDA label indicates that JCV antibody-negative patients have a lower risk of PML than those who are positive, though monitoring remains necessary 3
• The National Multiple Sclerosis Society guidelines support continuation of natalizumab therapy as long as proper risk stratification and monitoring are in place 1

Appropriate Monitoring is Documented

JCV Antibody Surveillance

• The patient has appropriate serial JCV antibody testing with most recent results showing negative status (index value 0.20-0.21), which is below the threshold for concern 4, 3
• The National Multiple Sclerosis Society recommends retesting JCV antibody status every 6 months to detect seroconversion in JCV antibody-negative patients, which this patient's care plan follows 4

MRI Surveillance Protocol

• Serial brain MRIs demonstrate stable disease with no evidence of PML or new MS activity 5
• The National Multiple Sclerosis Society recommends annual MRI surveillance for JCV antibody-negative patients, and this patient has appropriate imaging frequency documented 4
• The most recent MRI (stable abnormalities consistent with MS diagnosis, no clear evidence for PML) supports safe continuation 5

TOUCH Program Compliance

• The patient is appropriately enrolled and approved through the TOUCH program, which is mandatory for natalizumab administration due to PML risk 3
• The FDA label requires TYSABRI availability only through the restricted TOUCH Prescribing Program because of PML risk 3

Extended Interval Dosing (Every 6 Weeks) is Appropriate

• The patient receives natalizumab every 6 weeks rather than the standard every 4 weeks, which is associated with lower PML risk while maintaining disease control 6, 7
• The NOVA trial demonstrated that patients stable on every-4-week dosing who switched to every-6-week dosing maintained effective disease control with similar safety profiles 6, 7
• The European Committee for Treatment and Research in Multiple Sclerosis recommends that extended interval dosing can potentially reduce PML risk while maintaining efficacy 1

Specific Dates of Service Review

The infusions on the listed dates of service are medically necessary based on:

• Documented disease stability requiring ongoing disease-modifying therapy to prevent relapse 1
• Appropriate dosing interval (every 6 weeks) consistent with extended-interval protocols that reduce PML risk 6, 7
• Continued JCV-negative status at time of treatment supporting favorable risk-benefit ratio 4, 3
• Prior authorization history showing consistent approval pattern for this patient's ongoing therapy 1

Critical Safety Considerations

Ongoing Monitoring Requirements

• JCV antibody testing must continue every 6 months as the reported seroconversion rate is 3-8% annually, and serostatus can change intermittently 3
• Annual brain MRI remains appropriate for this JCV-negative patient, though more frequent imaging should be considered if seroconversion occurs 4
• Clinical vigilance cannot be replaced by testing schedules; any new neurological symptoms warrant immediate evaluation regardless of scheduled monitoring intervals 4

Risk-Benefit Assessment

• The patient's negative JCV status, lack of prior immunosuppression beyond failed MS therapies, and documented treatment failures with alternatives strongly favor continuation 1, 2
• Discontinuation risks include severe disease reactivation, which can increase morbidity and mortality risk 1
• The American Academy of Neurology emphasizes that natalizumab reduces measures of disease activity and improves measures of disease severity in relapsing-remitting MS patients 8

Conclusion on Medical Necessity

All three dates of service are medically necessary and appropriate. The patient demonstrates clear treatment response with disease stability, has failed alternative therapies, maintains low PML risk with negative JCV status, receives appropriate safety monitoring, and uses an extended dosing interval that further reduces risk. The absence of infusion notes for the specific dates does not negate medical necessity when the overall clinical picture, prior authorization history, and documented treatment plan support ongoing therapy at the prescribed interval.