This Tysabri (natalizumab) Dosing Calculator is designed to assist healthcare professionals in determining the next infusion date and stratifying patient risk for Progressive Multifocal Leukoencephalopathy (PML). It incorporates key risk factors outlined in the official prescribing information, including anti-JCV antibody status, treatment duration, and prior immunosuppressant use, to provide a comprehensive dosing and safety summary.

Upon entering the required patient data, the calculator provides the following key outputs:

• Next Dose Date: Calculates the exact date for the next scheduled 300 mg natalizumab infusion based on the last administration date and the selected dosing interval (4 to 8 weeks).
• PML Risk Estimate: Provides an estimated risk of developing PML, expressed as cases per number of patients (e.g., ~1 in 1,000). This stratification is based on the combination of anti-JCV antibody status, index value, duration of therapy, and history of prior immunosuppressant use.
• Pre-infusion Checklist: Generates a summary of essential clinical checks to perform before administration, including assessing for new neurological symptoms, reviewing for infections, and confirming lab results.
• Dosing Summary: Confirms the standard 300 mg dose and the chosen dosing schedule (Standard or Extended Interval Dosing).

To ensure an accurate dosing schedule and risk assessment, please provide the following information:

1. Last Dose Administration Date: Select the date the patient last received their Tysabri infusion.
2. Dosing Interval: Choose the appropriate interval in weeks (4 weeks for standard, 5-8 weeks for Extended Interval Dosing).
3. Anti-JCV Antibody Status: Select whether the patient is Positive, Negative, or Unknown for anti-John Cunningham virus (JCV) antibodies.
4. Anti-JCV Antibody Index Value: If the patient is anti-JCV antibody positive, enter their specific index value from the serology test. This input is disabled if the status is Negative or Unknown.
5. Prior Immunosuppressant Use: Indicate if the patient has a history of treatment with immunosuppressants (e.g., mitoxantrone, cyclophosphamide) before starting Tysabri.
6. Duration of Tysabri Therapy: Select the total length of time the patient has been on Tysabri therapy.

Tysabri (natalizumab) is administered as a 300 mg intravenous (IV) infusion over approximately one hour. The dose is not adjusted for patient body weight.

• Standard Dosing: The standard, approved dosing regimen is 300 mg every 4 weeks.
• Extended Interval Dosing (EID): Dosing every 6 weeks is an alternative regimen that may be considered for patients who are anti-JCV antibody positive, which may be associated with a reduced risk of PML. The safety and efficacy of other extended dosing intervals (5, 7, or 8 weeks) have not been established. The decision to use EID must be made by the treating clinician based on individual patient characteristics and risk-benefit assessment.
• Administration: Tysabri must be diluted in 100 mL of 0.9% Sodium Chloride Injection before administration. Patients should be monitored for at least one hour after the infusion for signs of hypersensitivity.

Switching to or from Tysabri requires careful clinical consideration to manage the risk of disease reactivation and opportunistic infections like PML.

• Switching to Tysabri: When switching from other disease-modifying therapies (DMTs), a washout period may be necessary. The duration depends on the previous drug’s mechanism of action and half-life. Special caution is needed when switching from immunosuppressants due to the increased risk of PML.
• Switching from Tysabri: When discontinuing Tysabri, the next DMT should be initiated based on a risk-benefit assessment. The immune effects of natalizumab can persist for approximately 12 weeks after the last dose.

If a patient misses a scheduled dose of Tysabri, the infusion should be administered as soon as possible. The subsequent dosing schedule should be reset from the date of this infusion. For example, if a dose is given 2 weeks late on a 4-week schedule, the next dose will be due 4 weeks after the make-up dose, not 2 weeks later. Do not administer double doses.

Contraindications: Tysabri is contraindicated in patients who have or have had PML and in patients with a history of hypersensitivity reaction to natalizumab or any of its components.

Why is the Anti-JCV Antibody Index Value important?
For patients who are anti-JCV antibody positive, the index value (or titer) provides a further level of risk stratification. A higher index value (e.g., >1.5) is associated with a higher risk of developing PML compared to a lower index value (e.g., ≤0.9).

What is Extended Interval Dosing (EID) and why is it used?
EID refers to administering Tysabri at intervals longer than the standard 4 weeks, most commonly every 6 weeks. Some evidence suggests EID may lower the risk of PML in anti-JCV antibody-positive patients, although its effect on efficacy compared to standard dosing is still under evaluation.

How does the calculator determine the PML risk category (Lower, Intermediate, Higher)?
The calculator uses a risk table derived from the official Tysabri prescribing information. It combines the three major risk factors (JCV status/index, treatment duration, prior immunosuppressant use) to find the corresponding estimated incidence of PML (cases per 1,000 patients).

Is the 300 mg Tysabri dose ever adjusted?
No, the recommended dose of Tysabri is 300 mg for all adult patients, regardless of body weight.

Why is prior immunosuppressant use such a critical risk factor?
Prior use of medications that suppress the immune system (like mitoxantrone, azathioprine, etc.) is an independent and significant risk factor for developing PML. It’s believed to compromise the immune system’s ability to control the JC virus, even before Tysabri is started.

How often should a patient’s Anti-JCV antibody status be re-tested?
For patients who initially test negative for anti-JCV antibodies, re-testing is recommended every 6 months, as seroconversion (becoming positive) can occur over time.

Does this calculator apply to the subcutaneous (SC) formulation of Tysabri?
This calculator is designed based on the principles of IV administration. While the dose is the same (300 mg), clinical guidance regarding administration and monitoring for the SC formulation may differ. Always consult the specific prescribing information for the formulation being used.

What should I do if a patient develops new neurological symptoms?
If a patient on Tysabri presents with any new, unexplained neurological symptoms, Tysabri should be withheld immediately, and a thorough diagnostic evaluation for PML (including an MRI of the brain and potentially CSF analysis) must be performed.

• TYSABRI® (natalizumab) injection, for intravenous use. Prescribing Information. Biogen Inc. Cambridge, MA. Updated January 2024. Available at: FDA.gov.
• Tysabri (natalizumab) Official HCP Website. Biogen. Accessed 2024. Available at: tysabrihcp.com.
• Tysabri (natalizumab) – European Medicines Agency (EMA) Summary of Product Characteristics. Available at: ema.europa.eu.
• Ryner, M., et al. (2021). Efficacy and safety of extended interval dosing of natalizumab in relapsing-remitting multiple sclerosis: a prospective observational study. *Therapeutic Advances in Neurological Disorders*, 14, 17562864211029285. Available at: ncbi.nlm.nih.gov.