Is Tysabri (Natalizumab) 300 milligrams intravenously every 28 days medically indicated for continuation for the diagnosis of multiple sclerosis?

Medical Indication for Continuation of Tysabri (Natalizumab) 300mg IV Every 28 Days for Multiple Sclerosis

Yes, continuation of Tysabri (natalizumab) 300 mg intravenously every 28 days is medically indicated for multiple sclerosis (G35), as discontinuation in clinically stable patients leads to disease reactivation or rebound activity, significantly increasing morbidity risk. 1

FDA-Approved Indication and Dosing

• The FDA-approved dose for multiple sclerosis is natalizumab 300 mg intravenous infusion over one hour every four weeks (28 days). 2
• Natalizumab is FDA-approved for relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. 1
• The medication demonstrates high efficacy in reducing annualized relapse rates, sustained disability progression, and MRI lesion activity compared to placebo. 3, 4

Rationale for Continuation Based on Clinical Outcomes

Patients with multiple sclerosis who are clinically stable on natalizumab should continue therapy indefinitely, as abrupt discontinuation can lead to severe disease reactivation, increasing both morbidity and mortality risk. 1

• Natalizumab significantly reduces annualized relapse rate and risk of sustained disability progression over 2 years compared to placebo. 3
• The medication significantly increases the proportion of relapse-free patients at 1 and 2 years. 3
• Continuation maintains disease control and prevents the well-documented rebound phenomenon that occurs after discontinuation. 1

Mandatory Risk Stratification and Monitoring Requirements

The continuation of natalizumab is medically appropriate only when proper risk stratification and safety monitoring protocols are implemented, as the primary safety concern is progressive multifocal leukoencephalopathy (PML). 1

Baseline and Ongoing JCV Antibody Testing

• Baseline JCV antibody testing with index value must be performed to establish PML risk stratification. 5
• For JCV antibody-negative patients: retest JCV antibody status every 6 months to detect seroconversion, as PML risk remains approximately 1 in 10,000. 5
• For JCV antibody-positive patients with index ≤1.5: retest JCV antibody index every 6 months to monitor for index increases. 5
• Patients with anti-JCV antibody index >1.5 have significantly elevated PML risk of approximately 1 in 855 overall. 5, 6

MRI Surveillance Protocol Based on Risk Stratification

All safety MRIs must include minimum sequences: T2, diffusion-weighted imaging (DWI), and FLAIR of the brain, performed and reported by a neuroradiologist or radiologist trained in PML identification. 5

• Mandatory MRI at 12 months for all patients on natalizumab, regardless of JCV status. 5
• JCV antibody-negative patients: Annual MRI surveillance after the 12-month baseline. 5
• JCV antibody-positive patients with index ≤1.5: MRI surveillance every 6 months minimum after 18 months of treatment. 5, 7
• JCV antibody-positive patients with index >1.5: MRI surveillance every 3-4 months after 18 months of treatment, as this represents high-risk status. 7, 5, 6

Critical Safety Considerations

• MRI evidence of PML may appear 3-6 months before symptom onset, making strict adherence to imaging schedules critical for early detection. 5
• Clinical vigilance cannot be replaced by testing schedules—any new neurological symptoms warrant immediate evaluation regardless of scheduled monitoring intervals. 5
• Early detection of PML followed by rapid cessation of natalizumab and plasma exchange to restore immune function is associated with improved prognosis. 7
• Asymptomatic patients diagnosed with PML have significantly better outcomes (mean EDSS 4.1) compared to symptomatic patients (mean EDSS 5.4), with overall survival of 96.7% versus 75.4% respectively. 7

Common Pitfalls and How to Avoid Them

• Pitfall: Failing to perform regular JCV antibody testing in seronegative patients, missing seroconversion events that dramatically increase PML risk. Solution: Implement strict 6-monthly JCV antibody retesting for all seronegative patients. 5
• Pitfall: Using inadequate MRI protocols that lack DWI sequences, reducing sensitivity for early PML detection. Solution: Ensure all safety MRIs include T2, DWI, and FLAIR sequences as minimum standard. 5, 7
• Pitfall: Discontinuing natalizumab prematurely due to PML concerns in low-risk patients, leading to preventable disease reactivation. Solution: Use risk stratification algorithms to guide continuation decisions rather than blanket discontinuation. 1
• Pitfall: Inadequate monitoring frequency in high-risk patients (JCV index >1.5, treatment >18 months). Solution: Implement mandatory 3-4 monthly MRI surveillance for this population. 7, 5

Treatment Duration Considerations

• Patients should continue natalizumab indefinitely as long as they remain clinically stable and proper monitoring is maintained. 1
• The estimated PML incidence is 1 per 1,000 patients treated for an average of 17.9 months, though this risk varies substantially based on JCV status and treatment duration. 4
• For patients with prior immunosuppressant use and JCV-positive status beyond 2 years of therapy, default to 3-4 monthly MRI frequency. 5

Prescriber Requirements

• Only prescribers registered in the MS TOUCH® Prescribing Program may prescribe natalizumab for multiple sclerosis. 2
• Enhanced pharmacovigilance including brain MRI every 3-4 months for up to 12 months is required if switching from natalizumab to other disease-modifying therapies (fingolimod, alemtuzumab, dimethyl fumarate) due to carry-over opportunistic infection risk. 7, 6