Low Placental Transfer Rates with Risankizumab Save

There are significant concerns about the safety of drug use during pregnancy and lactation, especially newer biologic agents. This is complicated by a lack of research. 

The neonatal fragment crystallizable receptor (FcRn), expressed on the placenta, transfers immunoglobulin from mother to infant starting at week 16 of gestation and increasing during the third trimester, when 80% of transfer occurs (increased placental surface area).  Normally, there is little monoclonal antibody exposure to the fetus during the first trimester, when organogenesis primarily occurs.  The risk of malformations with drug exposure is less important in the third trimester and post-partum.  These findings have been previously shown for TNF inhbitor therapy, ustekinumab, and vedolizumab.

Mahadevan and colleagues have studied placental transfer (part of their PIANO registry in IBD patients) with risankizumab (IgG1 monoclonal antibody against the p19 subunit of Interleukin (IL)-23). Uniquely RIZ has 2 mutations in the Fc region (Leu234Ala and Leu235Ala) which reduce Fcγ receptor interactions. They prospectively studied RIZ use in pregnant women before, during and after pregnancy and documented that RIZ does cross the placenta and is detectable in the infant at birth, but at lower levels than expected for an IgG1 antibody. 

They studied 3 women with Crohn’s disease, not taking concomitant immunosuppressive medications and two were in remission during pregnancy. There were 3 live births - one a healthy vaginal birth; the second infants was small for gestational age with intrauterine growth restriction born by cesarean section; and the third had polyhydramnios born by vaginal birth.

Serum levels of risankizumab in the newborn was detected in all three, at a fraction of maternal levels at birth. By comparison, mothers treated with ustekinumab, infant UST drug levels are generaly 1.5 times maternal levels compared to the infant. No serious infections in the infants were seen. 

Given these findings, it is the authors practice is to continue risankizumab throughout pregnancy and lactation, to maintain remission in the mother. Further studies on the safety of risankizumab in pregnant women with IBD are needed. 

This group (that specializes in the safety of DMARDs during pregnancy) suggests that Inactive vaccines are given on schedule (including rotavirus) and that the live BCG vaccine should be deferred until at least 6 months of age.