Is Adalimumab (adalimumab) safe to use during pregnancy?

Adalimumab Safety During Pregnancy

Adalimumab can be safely continued during pregnancy, particularly in the first and second trimesters, but should be discontinued in the third trimester if the patient's disease is well controlled to minimize fetal exposure. 1

Safety Profile by Trimester

First and Second Trimesters

• Adalimumab is considered safe during conception and early pregnancy
• The drug contains an IgG1 Fc construct that does not cross into fetal circulation in significant concentrations until the second trimester 1
• No increased risk of major birth defects has been observed with first-trimester exposure 2, 3

Third Trimester Considerations

• Adalimumab crosses the placenta significantly during the third trimester, resulting in high drug levels in the neonate 1
• If disease is well-controlled, discontinuation in the third trimester is recommended 1
• If active disease is present, continuing adalimumab through delivery can be considered, understanding that the neonate will have significant serum levels of the drug 1

Evidence on Birth Outcomes

• The Organization of Teratology Information Specialists (OTIS)/MotherToBaby registry showed a 10% rate of major birth defects with first-trimester adalimumab use in pregnant women with rheumatoid arthritis or Crohn's disease, compared to 7.5% in the disease-matched comparison cohort 2
• The lack of pattern in birth defects is reassuring 2
• The PYRAMID registry data showed that among 293 pregnancies with adalimumab exposure, 81.7% resulted in live births with only one case of congenital malformation reported 4

Disease-Specific Considerations

• For inflammatory bowel disease (IBD), maintaining remission during pregnancy is essential for both maternal and fetal outcomes 1
• Women with rheumatoid arthritis or Crohn's disease have an increased risk of preterm delivery regardless of adalimumab exposure 3
• Untreated active disease may pose greater risks than continuing medication during pregnancy 1

Practical Management Recommendations

1. Pre-conception planning:

   • Continue adalimumab while trying to conceive 1
   • Aim for disease remission before conception

2. During pregnancy:

   • Continue adalimumab through first and second trimesters
   • Consider discontinuation in third trimester if disease is well-controlled
   • Monitor disease activity regularly

3. Third trimester decision points:

   • If disease is in remission: discontinue adalimumab
   • If active disease: consider continuing, understanding neonatal exposure risks

4. Post-delivery considerations:

   • Live vaccines should be avoided in infants exposed to adalimumab in utero until drug clearance is documented or up to 1 year of age 5
   • Infliximab is cleared more slowly than adalimumab from infants (7.3 vs 4.0 months) 5

Important Caveats

• Combination therapy with thiopurines increases the relative risk of infant infections nearly 3-fold compared to anti-TNF monotherapy 5
• The benefits of controlling maternal disease often outweigh theoretical risks to the fetus
• Drug levels in the infant correlate inversely with time from last exposure during pregnancy 5
• The median ratio of infant:mother drug concentration at birth is 1.21 for adalimumab 5

While there are some risks associated with adalimumab use during pregnancy, the evidence suggests that maintaining disease control is paramount, and the medication can be used safely, particularly in the first and second trimesters.