Treatment of Inflammatory Bowel Disease with Biologics

83

IgG1 monoclonal antibody to TNFα approved for use in ulcerative colitis. As more
recent studies have shown that earlier treatment with these agents leads to improved
patient outcomes and prevents complications from their disease [ 15 ], the use of
these agents is becoming more common in younger patients, including women of
childbearing age.

Placental Transfer of Biologic Agents

Fetal immunity is achieved through the passive and active transfer of IgG from the
maternal circulation to the fetal circulation [ 16 ]. Active transfer occurs at the sur-
face of the syncytiotrophoblast placental layer through the selective binding of the
Fc gamma portion of the maternal IgG antibody to the Fc receptor neonatal mole-
cule which then transports the IgG antibody to the fetal circulation [ 17 ]. There is a
continuous, linear increase in the active transport of IgG starting at approximately
13 weeks of gestation and continually progressing until delivery [ 18 – 20 ]. There is a
preferential transport of IgG1 followed by IgG4, IgG3, and then IgG2, which is
important as many of the new medications used to treat inflammatory bowel disease
are IgG antibodies [ 21 ] (Table 6.2).
Anti-TNF agents with complete antibodies, including infliximab (IFX), adalim-
umab (ADA), and golimumab (GOL), are actively transported to the fetal circula-
tion through the mechanism described above. As certolizumab pegol (CZP) is a
fragmented Fc portion, it is only passively transferred from the maternal to fetal
circulation.
Several studies have confirmed the placental transfer of IFX and ADA as evi-
denced by detectable drug levels in cord blood [ 22 – 28 ]. In a prospective study look-
ing specifically at placental transfer of anti-TNF medications, Mahadevan et  al.
included 31 pregnant women with IBD (11 IFX, 10 ADA, and 10 CZP) and mea-
sured drug concentrations in the maternal serum, infant serum, and cord blood at the
time of birth then monthly in the infant serum until the drug concentrations were no

Table 6.2 Current biologic agents, molecular structure, and safety

Medication Molecular structure Safety in pregnancy Safety with breastfeeding

Infliximab Anti-TNF, IgG1 Low risk Compatible

Adalimumab Anti-TNF, IgG1 Low risk Compatible

Certolizumab

pegol

Anti-TNF, Fab’

fragment

Low risk, only passively

transferred to the fetus

Compatible

Golimumab Anti-TNF, IgG1 Low risk Compatible

Natalizumab Antihuman α 4

integrin, IgG4

Discontinue 3 months

prior to conception

Likely compatible,

limited studies in humans

Vedolizumab Antihuman α 4 β 7

integrin, IgG4

Low risk Likely compatible,

limited studies in humans

Ustekinumab Anti-IL-12/IL-23,

IgG1

Limited studies in

humans

Likely compatible,

limited studies in humans

6 Biologics in Pregnancy and Breastfeeding