91predict undetectable drug concentrations at birth.” [ 26 ] However, despite the vari-
ability in cord blood drug concentrations, no studies have shown an increase in
adverse neonatal outcomes that correlate with infant drug levels. Because of the
persistence of these drug levels, it is imperative that all live vaccines be held for at
least 6 months and possibly up to 1 year, in infants with a history of intrauterine
anti-TNF exposure.
Anti-integrin Agents
Currently, there are two anti-integrin medications available for treatment of inflam-
matory bowel disease. Natalizumab (Tysabri®, Biogen Idec) is a humanized mono-
clonal IgG4 antibody against the α4 subunit of the α 4 β1 and α 4 β7 integrin molecules
and is approved for the treatment of multiple sclerosis (MS) and Crohn’s disease.
Vedolizumab (Entyvio®, Takeda) is also a monoclonal IgG4 antibody that targets
only the α 4 β7 integrin molecule, making the mechanism of action more specific to
the gastrointestinal mucosa, approved for the treatment of ulcerative colitis and
Crohn’s disease.
Natalizumab
Studies of supratherapeutic doses of natalizumab (NAT) in animals have shown
mixed outcomes, including no fetotoxic or teratogenic effects [ 67 ] to increased
spontaneous abortion rate and hematologic effects including mild anemia and
thrombocytopenia [ 68 ]. The current recommendations are for anyone consider-
ing conception to discontinue NAT 3 months prior to conception due to the role
α4-integrins and their ligands play in mammalian development and due to the
absence of data on pregnancy and fetal outcomes following intrauterine exposure
to NAT. Several case reports of NAT exposure during pregnancy, including three
women with MS, have all resulted in healthy, full-term infants, one of which was
small for gestational age [ 69 – 71 ]. Several prospective studies of NAT exposure
during pregnancy in 137 women with MS have not showed an increase in adverse
pregnancy or fetal outcomes that could be attributed to NAT exposure [ 72 , 73 ]. A
study from the Tysabri (natalizumab) Pregnancy Exposure Registry (TPER), pre-
sented in abstract form, included 375 women with autoimmune diseases (368
with MS, 7 with Crohn’s disease) who were exposed to NAT within 90 days of
conception [ 74 ]. Of these pregnancies, there were 314 live births, 13 elective
abortions, 34 spontaneous abortions, 1 stillbirth, and 11 ongoing pregnancies,
and 10 women were lost to follow-up. The authors reported that in 28 pregnan-
cies in 26 women, major and/or minor defects were observed, but no further
details are provided. Overall, however, the study did not show any effect of NAT
exposure on pregnancy outcomes.
6 Biologics in Pregnancy and Breastfeeding