Recommended Use and Dosage of Tysabri (Natalizumab) for MS and Crohn's Disease
For multiple sclerosis and Crohn's disease, Tysabri (natalizumab) is administered as a 300 mg intravenous infusion over one hour every four weeks, but due to the risk of progressive multifocal leukoencephalopathy (PML), it is generally suggested against as first-line therapy and requires strict monitoring through specialized prescribing programs. 1
Multiple Sclerosis (MS) Recommendations
Indications
- Recommended for relapsing forms of MS in patients who have had an inadequate response to other disease-modifying therapies 2
- Not recommended as first-line treatment due to PML risk 3
Dosage and Administration
- 300 mg intravenous infusion over one hour every four weeks 1
- Must be prescribed through the MS TOUCH® Prescribing Program 1
- Preparation requires dilution in 100 mL of 0.9% Sodium Chloride Injection, USP 1
Monitoring Requirements
- Anti-JCV antibody testing every six months to stratify PML risk 4
- MRI monitoring frequency should be adjusted according to individual PML risk factors:
- Duration of treatment (risk increases after 24 months)
- Prior immunosuppressant use
- Anti-JCV antibody status and index level 4
- Baseline MRI before treatment initiation and follow-up MRI scans 4
Risk Stratification for PML
- PML risk factors:
- Positive anti-JCV antibody status
- Prior use of immunosuppressants
- Duration of treatment (especially beyond 24 months) 4
- Risk increases from 1/1000 (1-24 months) to 5-6/1000 (after 24 months) in JCV-positive patients without prior immunosuppressant use 4
- Risk increases to 11/1000 after 25-48 months in patients with prior immunosuppressant use 4
Crohn's Disease Recommendations
Indications
- For moderate-to-severe Crohn's disease in patients with inadequate response to conventional therapy 4
- The AGA suggests against the use of natalizumab for induction and maintenance of remission in Crohn's disease 4
Dosage and Administration
- 300 mg intravenous infusion over one hour every four weeks 1
- Must be prescribed through the CD TOUCH® Prescribing Program 1
- Important restrictions:
- Should not be used with concomitant immunosuppressants (6-mercaptopurine, azathioprine, cyclosporine, methotrexate) or TNF-α inhibitors
- Aminosalicylates may be continued during treatment 1
Treatment Duration Guidelines
- Discontinue if no therapeutic benefit after 12 weeks of induction therapy
- For patients on corticosteroids:
- Begin steroid tapering once therapeutic benefit occurs
- Discontinue Tysabri if patient cannot be tapered off steroids within 6 months
- Consider discontinuation if additional steroid use exceeds 3 months in a calendar year 1
Safety Considerations for Both Indications
PML Risk Management
- Anti-JCV antibody testing before initiation and periodically during treatment 4
- Higher risk in patients who:
- Are anti-JCV antibody positive (especially with high index values)
- Have used prior immunosuppressants
- Have received treatment for more than 24 months 4
Contraindications
- History of PML
- Immunocompromised patients
- Concurrent use of immunosuppressants (for Crohn's disease) 1
Special Populations
- Pregnancy: Limited data available
- Breastfeeding: Natalizumab transfers into breast milk with accumulation over time (relative infant dose up to 5.3% of maternal dose) 5
Monitoring During Treatment
- Regular clinical assessment for new or worsening neurological symptoms
- MRI screening for early PML detection
- Anti-JCV antibody testing every 6 months 4
- Immediate discontinuation if PML is suspected
Treatment Discontinuation
- Perform MRI scan when discontinuing natalizumab
- Conduct a "safety scan" 3 months after the end of treatment before starting any new therapy 4
The risk of PML must be carefully weighed against the potential benefits of natalizumab therapy. For Crohn's disease specifically, the AGA suggests against using natalizumab given the availability of other effective therapies with better safety profiles 4.