Is Tysabri (natalizumab) safe to use during pregnancy?

Natalizumab (Tysabri) Use During Pregnancy

Natalizumab should be discontinued before pregnancy when possible, but if treatment is needed during pregnancy due to highly active multiple sclerosis, continuation until the end of the first trimester appears to offer better maternal outcomes with acceptable fetal risk. 1

Safety Profile and FDA Guidance

The FDA label for natalizumab (Tysabri) indicates there are no adequate data on the risk of major birth defects, miscarriage, or other adverse maternal outcomes associated with its use during pregnancy 1. However, important safety concerns include:

• Neonatal thrombocytopenia (sometimes with anemia) has been reported in infants exposed to natalizumab in utero
• Animal studies showed immunological and hematologic effects in fetuses at doses similar to human doses
• A CBC should be obtained in neonates who were exposed to natalizumab in utero

Pregnancy Registry Data

The Tysabri Pregnancy Exposure Registry provides important insights:

• Among 355 pregnancies with known outcomes, the spontaneous abortion rate was 9.0% (within normal population range)
• The major birth defect rate was 5.05%, which is higher than general population but showed no specific pattern of malformations suggesting a drug effect 2
• Mean gestational age of live-born infants was 38.3 weeks with mean birth weight of 3158.3g 2

Management Algorithm for MS Patients Requiring Natalizumab

1. Pre-pregnancy planning (ideal scenario):

   • Discontinue natalizumab 3 months before conception
   • Consider alternative MS treatments with better pregnancy safety profiles

2. For unplanned pregnancies discovered while on natalizumab:

   • For patients with highly active MS:

     • Consider continuing natalizumab until the end of first trimester (week 12-14)
     • This "secured first trimester" approach shows significantly lower relapse rates (3.6% vs 38.5%) and disability progression (3.6% vs 30.8%) compared to stopping at conception 3

   • For patients with stable disease:

     • Discontinue natalizumab immediately

3. For patients requiring continued treatment during pregnancy:

   • Consider implementing a protocol similar to NAP-30:
     • Adjust dosing to every 6 weeks during pregnancy up to week 30
     • Schedule delivery at week 40
     • Restart natalizumab within 2-4 days after delivery 4

4. Monitoring during pregnancy if natalizumab is continued:

   • Regular maternal neurological assessments
   • Fetal ultrasound monitoring
   • CBC monitoring of newborn after delivery

Important Considerations and Caveats

• The decision to use natalizumab during pregnancy must balance maternal benefit against potential fetal risk
• Natalizumab crosses the placenta, particularly in the third trimester
• Stopping natalizumab in patients with highly active MS can lead to severe rebound disease activity
• A comparative study found that women who maintained natalizumab through the first trimester had significantly better MS outcomes than those who stopped at conception 3
• Case reports exist of successful pregnancies with natalizumab continued throughout the entire pregnancy, but this approach carries higher risk of fetal exposure 5

Postpartum Considerations

• Restart natalizumab promptly after delivery (within 2-4 days) to prevent postpartum relapses
• Monitor the infant for potential hematologic abnormalities, particularly thrombocytopenia and anemia
• Breastfeeding while on natalizumab is not well-studied and generally not recommended

The decision to use natalizumab during pregnancy should prioritize maternal neurological stability while minimizing fetal exposure, particularly avoiding third-trimester use when transplacental transfer is highest.