Duration of Tysabri Every 6-Week Infusion Protocol
Patients with multiple sclerosis can be treated with Tysabri on an every 6-week infusion protocol indefinitely as long as they remain clinically stable and adhere to appropriate PML risk-stratified monitoring protocols, with no predetermined maximum duration established in current guidelines. 1
Evidence for Extended Duration Safety
The NOVA randomized controlled trial demonstrated that patients stable on natalizumab for ≥12 months who switched to every 6-week dosing maintained effective disease control through 72 weeks, with no significant differences in disability progression, cognitive function, or clinical outcomes compared to standard 4-week dosing. 2 This provides direct evidence supporting the safety and efficacy of extended interval dosing for at least 1.5 years after switching.
Long-term observational data from the Tysabri Observational Program (TOP) followed patients for up to 5 years and demonstrated sustained low annualized relapse rates (0.31) and stable disability scores without new safety signals beyond PML, supporting indefinite continuation with appropriate monitoring. 3
Critical PML Risk Stratification Requirements
The decision to continue every 6-week dosing indefinitely must be coupled with risk-stratified PML surveillance that intensifies based on three key factors: JCV antibody status, antibody index level, and treatment duration beyond 18 months. 4
For JCV Antibody-Negative Patients:
- PML risk remains approximately 1 in 10,000 5
- Retest JCV antibody status every 6 months to detect seroconversion 5
- Annual brain MRI surveillance (minimum T2, DWI, FLAIR sequences) 4, 5
For JCV Antibody-Positive Patients with Index ≤1.5:
- PML risk approximately 1 in 5,882 5
- Retest antibody index every 6 months to monitor for increases 5
- MRI surveillance every 6 months minimum after 18 months of treatment 4, 5
For JCV Antibody-Positive Patients with Index >1.5:
- PML risk approximately 1 in 855 overall, increasing to 1 in 113 during months 25-48 of therapy 4, 5
- MRI surveillance every 3-4 months after 18 months of treatment 4, 5, 6
- Further antibody index testing not mandatory as risk is already established as high 4
Enhanced Monitoring for High-Risk Scenarios
Patients with prior immunosuppressant use who are JCV-positive and beyond 2 years of natalizumab therapy should default to 3-4 monthly MRI frequency regardless of antibody index. 5 This population demonstrated PML incidence of 11 per 1,000 after 25-48 months of exposure compared to 5 per 1,000 in immunosuppressant-naïve patients. 4
All safety MRIs must be performed and reported by a neuroradiologist or radiologist specifically trained in PML identification, as MRI evidence of PML may appear 3-6 months before symptom onset. 4, 5, 6
Critical Safety Considerations for Indefinite Treatment
The American Academy of Neurology emphasizes that abrupt discontinuation of natalizumab can lead to severe disease reactivation, increasing both morbidity and mortality risk. 1 This creates a clinical imperative to continue therapy in stable patients rather than arbitrarily stopping based on duration alone.
However, clinical vigilance cannot be replaced by testing schedules—any new neurological symptoms warrant immediate evaluation regardless of scheduled monitoring intervals. 5 Early detection of asymptomatic PML followed by rapid cessation and plasma exchange is associated with dramatically improved outcomes: 96.7% overall survival in asymptomatic patients versus 75.4% in symptomatic patients. 1
Practical Algorithm for Continuation Decisions
At 18 months of treatment: Reassess risk stratification and intensify MRI monitoring based on JCV status and index 4, 5
At 24 months of treatment: The greatest increase in PML risk occurs after this threshold (from 0.6 per 1,000 in months 1-24 to 5.2 per 1,000 in months ≥25 for JCV-positive patients) 4—this is the critical decision point for shared decision-making about continuation
Beyond 48 months: Limited data exist for this population, though estimated PML risk is 5.4 per 1,000 after 49-72 months of exposure in immunosuppressant-naïve patients 4—continuation requires explicit discussion of uncertain long-term risk-benefit ratio
If switching therapies: Enhanced pharmacovigilance including brain MRI every 3-4 months for up to 12 months is required due to carry-over opportunistic infection risk 4, 1
Common Pitfalls to Avoid
Do not assume that every 6-week dosing reduces PML risk sufficiently to relax monitoring schedules—the extended interval may lower risk compared to 4-week dosing, but all risk stratification and monitoring recommendations remain based on cumulative exposure duration and JCV status, not dosing interval. 4
Do not continue therapy indefinitely in high-risk patients (JCV-positive with index >1.5 beyond 24 months) without explicit informed consent discussions at regular intervals, as the risk-benefit calculation becomes increasingly unfavorable with longer duration. 4