乌鸦传媒

In utero exposure to ustekinumab (Stelara) or vedolizumab (Entyvio) proved as safe as other treatments for inflammatory bowel disease (IBD) during pregnancy, according to an updated analysis from the PIANO registry.

Among over 1,600 pregnant women with IBD, exposure to the two drugs was not associated with a greater risk of maternal or neonatal complications compared with tumor necrosis factor (TNF) inhibitors, immunomodulators, biologics combined with immunomodulators, as well as no exposure to any of these medications.

Furthermore, no significant differences were seen with ustekinumab and vedolizumab versus the comparator groups when it came to any pregnancy complication (25.6% with ustekinumab and 16.9% with vedolizumab; P=0.663), or for spontaneous abortion, small-for-gestational age, intrauterine growth restriction, low birth weight, neonatal intensive care unit (NICU) stays, and congenital malformations.

Lower rates of preterm births -- <37 gestational weeks -- were seen among those who received ustekinumab (0%, P=0.037), as were lower cesarean section rates (31.6%, P=0.024), reported Rishika Chugh, MD, of the University of California San Francisco, during her presentation at the American College of Gastroenterology annual meeting.

From birth up to 1 year, there were no significant differences in rates of infections among all groups.

"At this time, continuation of ustekinumab and vedolizumab is recommended during pregnancy," Chugh said, but "there are still safety concerns surrounding these medications due to a lack of and conflicting available data."

Vedolizumab may affect the MAdCAM-1 gene, which could play a role in placental development; ustekinumab is an interleukin (IL)-12 and IL-23 blocker, and both elevated and absent levels of IL-12 and IL-23 may be associated with spontaneous abortion, Chugh explained.

However, in commenting on the study, Russell Cohen, MD, of the University of Chicago Medicine, noted that "the take-home message is that we continue to encourage patients and providers to continue FDA-approved monoclonal biologics in patients before, during, and after pregnancy."

A recent study found no higher risk of adverse events with TNF inhibitor exposure during pregnancy, and previous results from the found that biologics and thiopurines were safe during pregnancy, but only assessed small numbers of patients.

For their updated analysis, Chugh and colleagues examined data on 1,642 completed singleton pregnancies in women with IBD. Of these women, 700 were taking TNF inhibitors, 226 were on immunomodulators, 62 were receiving vedolizumab, 43 were receiving ustekinumab, 179 were taking a combination of biologics plus immunomodulators, and 430 had no exposure to any of these medications.

Among all groups, the mean maternal age was 32-33 at delivery. More patients in the ustekinumab group had Crohn's disease than ulcerative colitis (84% vs 16%), while those in the vedolizumab group were more evenly split (48% vs 52%). Ustekinumab patients had a longer disease duration than those in the vedolizumab group (13.7 vs 9.6 years).

Ustekinumab concentrations were higher at birth in infants (4.9 µg/mL) and in infants or cord (4.9 µg/mL) compared with in mothers (3.4 µg/mL), while vedolizumab concentrations were lower in infants (9.6 µg/mL) and infants or cord (9.1 µg/mL) versus mothers (13 µg/mL).

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