92
Looking specifically at NAT exposure during the third trimester, a recent case
series of 13 pregnancies in 12 women with severe MS who continued treatment with
NAT throughout the pregnancies due to severe relapsing disease refractory to other
therapies reported thrombocytopenia (n = 6) and anemia (n = 8) in 10 of the 13
infants, which resolved by approximately 4 months of age [ 75 ]. One infant was born
small for gestational age with subsequent developmental delay at 1 year of age after
the mother developed a catastrophic relapse which required intense treatment. At
the time of delivery, another infant was noted to have ultrasound findings of a cystic
formation in the brain, possibly due to an intracranial hemorrhage; however, as
previously reported [ 76 ], this was no longer detectable at 12 weeks of age, and the
child had no developmental delay as of 2 years of age. In a recent study from the
PIANO registry, pregnancy outcomes following exposure to biologics in T3 included
nine subjects who were exposed to NAT and found no differences in the outcomes
between study groups [ 59 ]. A recent, large prospective observational study included
101 women with MS exposed to NAT during T1 and compared pregnancy and fetal
outcomes to a disease-matched (DM) cohort not exposed to NAT and to a healthy
control (HC) group [ 77 ]. There were higher rates of miscarriage (17.3% NAT
exposed, 21.1% DM vs. 4.1% HC, P = 0.0004) and lower birth weights (3159 ± 478.9
grams NAT exposed, 3198.3 ± 515.3 g DM vs. 3436.7 ± 549.5 g in HC, P=0.001)
in the NAT exposed and DM cohorts compared to HC, but there were no significant
differences in the outcomes of the NAT exposed compared to the DM cohort. In
addition, there were no differences in the rates of major malformations or premature
births between all cohorts. These recent studies have not shown a correlation
between NAT exposure in pregnancy and adverse pregnancy or fetal outcomes.
Vedolizumab
Due to its recent FDA approval, the data on the safety of vedolizumab (VDZ) use in
pregnancy is limited to data from the VDZ clinical development program, which
included 24 pregnancies in women exposed to VDZ, resulting in 11 (45.8%) live
births, 2 premature, and 1 (4.16%) congenital anomaly 79 days after a single dose
of VDZ in a healthy volunteer with prior pregnancies complications [ 78 ]. This
descriptive abstract provides some insight into the pregnancy outcomes following
exposure to VDZ; however, further studies are clearly needed.
Anti-IL-12/IL-23 Agents
Ustekinumab (UST) is a human monoclonal antibody that decreases cytokine activ-
ity by binding to the p40 subunit on both IL-12 and IL-23. It has completed clinical
trials for the treatment of Crohn’s disease and is projected to be FDA approved for
this treatment indication later in 2016; however, it has been available for treatment
J.K.J. Gaidos and S.V. Kane