What is the preferred Tumor Necrosis Factor alpha (TNF-alpha) inhibitor for breastfeeding patients?

TNF-α Inhibitor Selection for Breastfeeding Patients

Certolizumab pegol is the preferred TNF-α inhibitor for breastfeeding patients due to its unique Fc-free molecular structure that results in minimal to no transfer into breast milk, with an average relative infant dose of only 0.15% of the maternal dose. 1

Why Certolizumab is Preferred

• Certolizumab demonstrates minimal to no placental transfer during pregnancy and virtually undetectable breast milk transfer during lactation due to its pegylated Fab fragment structure lacking the Fc portion that facilitates active transport 1, 2

• The CRADLE study found that 56% of breast milk samples had no measurable certolizumab, and for 4 out of 17 mothers, all samples were below the lower limit of quantification 1

• The estimated average daily infant dose was 0-0.0104 mg/kg/day, with a median relative infant dose of 0.15%—well below the 10% threshold considered clinically concerning 1

• Even if trace amounts reach breast milk, oral bioavailability is extremely low, making infant absorption via breastfeeding highly unlikely 1

Other Appropriate TNF-α Inhibitors for Breastfeeding

While certolizumab is preferred, infliximab and adalimumab are also considered safe and appropriate options during breastfeeding based on guideline recommendations and registry data:

Infliximab

• Case reports demonstrate no or low levels in breast milk, with no detectable levels in the sera of breastfed infants in one series of 3 cases 3
• Another study found low levels 5 days after infusion, but these were not clinically significant 3
• The Toronto Consensus statements (2016) concluded there are no compelling reasons to discontinue infliximab during breastfeeding 3

Adalimumab

• Low levels reported in breast milk but undetectable in infant sera 9 days after administration 3
• The PIANO registry found no significant increase in infections in infants associated with adalimumab exposure during breastfeeding 3

Etanercept

• While less data exists specifically for IBD, the 2019 AAD-NPF guidelines state that TNF-α inhibitors are safe during lactation 3
• Limited human data suggest no increased toxicity to breastfed infants 3

Golimumab

• Included in the general safety profile of TNF-α inhibitors during breastfeeding 3
• Minimal transfer expected due to large molecular weight similar to other monoclonal antibodies

Clinical Algorithm for Selection

Step 1: Assess disease control needs

• If initiating new therapy or switching agents → strongly consider certolizumab as first choice 1, 2
• If already well-controlled on infliximab or adalimumab → continuation is safe and appropriate 3

Step 2: Consider practical factors

• Certolizumab: subcutaneous administration, 200 mg every 2 weeks or 400 mg every 4 weeks 1
• Infliximab: intravenous infusion, may be preferred if patient already has established access and tolerates infusions well 3
• Adalimumab: subcutaneous administration, convenient for home use 3

Step 3: Patient counseling

• All TNF-α inhibitors transfer into breast milk in minimal amounts that are unlikely to be absorbed by the infant's gastrointestinal tract 3
• The decision to breastfeed should be made independent of TNF-α therapy, considering advantages to the newborn and patient preference 3
• There is no evidence to support discarding breast milk or timing breastfeeding around medication administration 3

Critical Safety Consideration for Infants

If the mother received TNF-α inhibitors during pregnancy (particularly third trimester), defer live vaccinations in the infant until 6 months of age due to potential in utero exposure and transplacental transfer 3. This applies regardless of breastfeeding status. Standard non-live vaccines should proceed on schedule 3.

Common Pitfalls to Avoid

• Do not unnecessarily switch a patient who is well-controlled on infliximab or adalimumab simply because they are breastfeeding—these agents are safe 3
• Do not advise patients to "pump and dump" or time breastfeeding around doses—there is no evidence supporting this practice for TNF-α inhibitors 3
• Do not confuse pregnancy recommendations with breastfeeding recommendations—while some sources suggest stopping TNF-α inhibitors in the third trimester of pregnancy, this does not apply to breastfeeding 4, 5
• Ensure infant vaccination schedules account for in utero exposure if applicable 3