What are the risks of administering intravenous (IV) rituximab (rituximab) during pregnancy?

Risks of IV Rituximab During Pregnancy

IV rituximab during pregnancy primarily causes B-cell depletion in newborns, though spontaneous recovery typically occurs, and should only be used when maternal benefit significantly outweighs fetal risks. 1

Primary Risks to the Fetus

• Administration of rituximab during pregnancy in patients with B-cell lymphoma increases the risk of B-cell depletion in newborns 1
• Dosing in the second half of pregnancy puts the fetus at high risk of having minimal B cells at delivery 1
• Rituximab crosses the maternofetal barrier and may potentially affect the developing immune system 1
• The FDA label indicates that rituximab can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed in-utero 2

Clinical Evidence and Recommendations

• According to ESMO guidelines, rituximab administration during pregnancy should not be discouraged in patients where postponement would significantly compromise maternal prognosis 1
• The American College of Rheumatology conditionally recommends continuing rituximab during pregnancy only if severe life- or organ-threatening maternal disease warrants it 1
• Spontaneous recovery of neonatal B cell counts has been observed in all reported cases of B-cell depletion 1
• Rituximab can be detected postnatally in the serum of infants exposed in-utero 2

Safety Data from Case Reports

• In a case series of 19 women exposed to rituximab, no pattern of major structural anomalies or other adverse outcomes was reported, and no cases of B cell depletion were documented 3
• In a larger review of 231 pregnancies with maternal rituximab exposure, most cases were confounded by concomitant use of potentially teratogenic medications 4
• Of 153 pregnancies with known outcomes in this review, 90 resulted in live births with only two congenital malformations identified (clubfoot in one twin and cardiac malformation in a singleton birth) 4
• Eleven neonates had hematologic abnormalities without corresponding infections, and four neonatal infections were reported 4

Timing Considerations

• The risk of B-cell depletion is higher when rituximab is administered in the second half of pregnancy due to increased placental transfer 1, 2
• In case reports of rituximab exposure during the first trimester, the low transplacental maternofetal transfer during this period may explain favorable outcomes 5

Recommendations for Clinical Practice

• Women should be counseled to avoid pregnancy for at least 12 months after rituximab exposure 1, 2, 4
• If pregnancy occurs during rituximab treatment, patients should be informed that this approach may influence fetal immunity for some time 1
• If a pregnancy is exposed to rituximab, the baby should avoid live vaccines for at least the first 6 months of life 1
• Women should not breastfeed while receiving rituximab and for up to 12 months following the last infusion 1, 2

Decision Algorithm

1. Assess maternal disease severity and need for rituximab
2. If rituximab is absolutely necessary for life- or organ-threatening maternal disease:
   • Consider timing of administration (earlier in pregnancy has lower risk of fetal B-cell depletion)
   • Inform patient about risks of B-cell depletion in the newborn
   • Monitor fetal development closely
3. If maternal disease can be controlled with pregnancy-compatible alternatives, defer rituximab until after delivery
4. For women already on rituximab who become pregnant, continue close monitoring and inform about potential risks to the fetus