What is the recommended dose of natalizumab (Tysabri) for patients with relapsing-remitting multiple sclerosis?

Recommended Dosing of Natalizumab (Tysabri) for Relapsing-Remitting Multiple Sclerosis

The recommended dose of natalizumab for relapsing-remitting multiple sclerosis is 300 mg administered as an intravenous infusion over one hour every four weeks. 1

Dosing Protocol

• Natalizumab must be administered by healthcare providers registered in the MS TOUCH® Prescribing Program due to the risk of progressive multifocal leukoencephalopathy (PML) 1
• The standard dose is 300 mg intravenous infusion over one hour every four weeks 1
• To prepare the solution:
  • Withdraw 15 mL of natalizumab from the vial using a sterile needle and syringe 1
  • Inject into 100 mL of 0.9% Sodium Chloride Injection, USP 1
  • Gently invert to mix completely (do not shake) 1
  • The final diluted solution has a concentration of 2.6 mg/mL 1

Administration Guidelines

• Infuse natalizumab 300 mg in 100 mL 0.9% Sodium Chloride Injection over approximately one hour (infusion rate approximately 5 mg per minute) 1
• Do not administer as an intravenous push or bolus injection 1
• After infusion completion, flush with 0.9% Sodium Chloride Injection, USP 1
• Observe patients during all infusions for potential hypersensitivity reactions 1

Efficacy and Alternative Dosing Considerations

• The standard 300 mg every 4 weeks (Q4W) dosing regimen has been proven effective in reducing relapse rates by 68% and disability progression by 42% compared to placebo 2
• Extended interval dosing (every 6 weeks) has been studied as a potential strategy to reduce PML risk, but showed numerically higher lesion activity compared to the standard 4-week interval 3
• The REFINE study demonstrated that 300 mg Q4W dosing is superior to 12-week interval dosing, which was associated with increased clinical and MRI disease activity 4

Safety Monitoring Requirements

• All patients should undergo anti-JCV antibody testing before initiating treatment to assess PML risk 5, 6
• Risk stratification for PML should be based on:
  • Anti-JCV antibody status and index value 5, 6
  • Duration of natalizumab therapy 5, 6
  • Prior use of immunosuppressants 5, 6
• MRI monitoring recommendations based on risk factors:
  • JCV antibody-negative patients: Annual MRI assessment 6
  • JCV antibody-positive with index ≤1.5: MRI every 6 months after 18 months of therapy 5
  • JCV antibody-positive with index >1.5: MRI every 3-4 months after 18 months of therapy 5, 6
• The MRI protocol should include FLAIR, T2-weighted, and diffusion-weighted imaging 6

Important Considerations and Warnings

• Natalizumab increases the risk of PML, an opportunistic viral infection of the brain that can lead to death or severe disability 1
• PML risk varies significantly based on risk factors:
  • JCV antibody-negative patients: approximately 1 in 10,000 5, 6
  • JCV antibody-positive with index ≤1.5: approximately 1 in 5,882 5, 6
  • JCV antibody-positive with index >1.5: approximately 1 in 855 5, 6
• Natalizumab should be used as monotherapy and not combined with immunosuppressants or TNF-α inhibitors 1
• Patients switching from natalizumab to other therapies require continued vigilance with MRI monitoring for up to 12 months after discontinuation 6

Treatment Discontinuation Considerations

• When discontinuing natalizumab, a "safety scan" MRI is recommended 3 months after the end of treatment 5
• Patients switching to other disease-modifying therapies after natalizumab should be closely monitored, as disease reactivation can occur 7