Monoclonal Antibody Drugs in Breastfeeding Moms

Monoclonal antibodies are molecules created in a lab to function like antibodies of the immune system and are important in the treatment of organ transplant, chronic inflammatory diseases like rheumatoid arthritis and inflammatory bowel disease, neurological diseases like multiple sclerosis, and certain cancers. These antibodies are made by immune cells that are identical clones of a starting parent cell (hence the “clonal” part of monoclonal) and are designed to bind to a specific antigen. For example, a monoclonal antibody created to treat an inflammatory condition could bind to a signaling molecule to prevent the activation of an autoimmune response. Generic drug names for monoclonal antibodies end in –mab.

Women with chronic inflammatory conditions often experience flares after pregnancy, which can leave breastfeeding mothers feeling like they have to choose between treating their symptoms and feeding their baby.  Passage of molecules into breastmilk requires a few conditions to be met. After delivery when milk production begins in earnest, open spaces between mammary epithelial cells begin to close and are fully closed two weeks postpartum¹. Without these open spaces, molecules have to either be small enough to go through aqueous channels or fit criteria based on charge, molecular weight, how the molecule interacts with the pH, and on protein-binding. The drug most likely to pass into breastmilk would be small, uncharged or minimally charged, and not protein-bound. The accepted size cutoff for passage into breastmilk is 800 Da. Since monoclonal antibodies are 140,000 Da and charged, we would not expect to see any in breastmilk.

However, some studies have found monoclonal antibodies in breastmilk. While these drugs are assumed to have poor oral absorption due to large size and breakdown in the digestive system, their use during lactation falls under “use with caution”. If case studies have found evidence of monoclonal antibodies in breastmilk, a manufacturer warning label will read “manufacturer recommends breast feeding be discontinued during therapy”¹. Experts agree that monoclonal antibodies designed for treatment of rheumatoid arthritis and inflammatory bowel disease are compatible breastfeeding. In fact, breastfeeding may have a protective effect on flare ups². No similar recommendations have been made for medications that treat multiple sclerosis. Specific monoclonal antibodies will be discussed below.

Rituximab is a monoclonal antibody that targets CD20 on B cells and is used to treat rheumatoid arthritis, vasculitis, and certain kinds of cancer like Non-Hodgkin’s Lymphoma and Chronic Lymphoid Leukemia. A case report of a 34-year-old mother with granulomatosis with polyangiitis found minimal excretion of the drug into breast milk, <240 times the amount in maternal serum³. More data are required to prove safety, and experts have not reached consensus. Manufacturer recommends discontinuing breastfeeding until 6 months after treatment, while some experts a cessation only if less than 2 weeks postpartum or after receiving a dose. The minimal excretion combined with poor oral bioavailability suggests breast feeding should probably not be discouraged in women who need treatment.

Infliximab targets TNF-alpha and is used to treat autoimmune diseases. A few reports found peak excretion is 1 to 4 days post infusion and has been found at low levels in breastmilk, 0.5% maternal serum concentration which is below the arbitrary acceptable cutoff level of 10%³. Experts consider Infliximab compatible with breastfeeding while exercising caution.

Certolizumab pegol is another monoclonal antibody directed against TNF-alpha and is used to treat Crohn's disease, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This monoclonal antibody is the only PEGylated anti-TNF without Fc region, the part of the antibody thought to be involved in intestinal uptake⁴. The prospective, multicenter, pharmacokentic study CRADLE found minimal passage of certolizumab into breastmilk with a relative infant dose 0.04% to 0.35%, which is below the 10% cutoff, and no passage of PEG⁴. During the study, nasopharyngitis was reported in one breastfed infant. Combined with poor bioavailability, the findings supported continuing treatment during breast feeding while exercising caution. 

Vedolizumab is designed to bind to an integrin protein in the digestive tract and is used to treat inflammatory bowel diseases.  A prospective observational study found it present at low levels in breastmilk, peaking at 3 to 4 days post infusion⁵.  Vedolizumab is detectable in breastmilk at any given time in between infusions, but its peak concentration is less than 1% maternal serum concentration, below the 10% cutoff⁶. Experts consider Vedolizumab compatible with breastfeeding while exercising caution.

Table 1: Biologic Medications for Inflammatory Bowel Disease During Lactation, based on limited data
Source: Mahadevan et al. Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease. Gastroenterology. 2017 Jan; 152(1):451–462

In conclusion

• A general rule: use with caution as a blanket statement and continue when being treated for inflammatory conditions.
• Most monoclonal antibodies used in the treatment of inflammatory bowel diseases are compatible with breastfeeding.  
• Studies for certolizumab pegol support continued use during breast feeding term infants and with caution in preterm infants.
• More data is needed

1. Anderson P. Monoclonal Antibodies. Breastfeeding Medicine. 2016; 11(3):100-101.

2. Mahadevan U, McConnell R, Chambers C. Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease. Gastroenterology. 2017 Jan; 152(1):451–462.

3. Bragnes Y, Boshuizen R, de Vries A, Lexberg Å, Østensen M. Low level of Rituximab in human breast milk in a patient treated during lactation. Rheumatology (Oxford). 2017 Jun 1;56(6):1047-1048.

4. Clowse ME, Förger F, Hwang C, Thorp J, Dolhain RJ, van Tubergen A, Shaughnessy L, Simpson J, Teil M, Toublanc N, Wang M, Hale TW. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017

Nov;76(11):1890-1896.

5. Lahat A, Shitrit AB, Naftali T, Milgrom Y, Elyakim R, Goldin E, Levhar N, Selinger L, Zuker T, Fudim E, Picard O, Yavzori M, Ben-Horin S. Vedolizumab Levels in Breast Milk of Nursing Mothers With Inflammatory Bowel Disease. J Crohns Colitis. 2018 Jan 5;12(1):120-123.

6. Julsgaard M, Kjeldsen J, Bibby BM, Brock B, Baumgart DC. Vedolizumab Concentrations in the Breast Milk of Nursing Mothers With Inflammatory Bowel Disease. Gastroenterology. 2018 Feb;154(3):752-754.

Kendall Marshall, MS4
Thomas W. Hale Ph.D.

InfantRisk Center