S719 Maternal and Neonatal Outcomes in Vedolizumab and Ustekinumab Exposed Pregnancies: Results From the PIANO Registry

Abstract

Introduction: Pregnancy outcomes in IBD patients with quiescent disease are similar to the general population. Data from the Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) registry have demonstrated the safety of anti-tumor necrosis factor alpha (TNFs) and thiopurines in pregnancy. The objective of this study is to provide updated information from the PIANO registry on maternal and fetal outcomes in patients exposed to ustekinumab (UST) and vedolizumab (VDZ). Methods: In this multicenter prospective observational study, we included pregnant women with singleton pregnancies and a diagnosis of inflammatory bowel disease. Questionnaires were administered to women at study intake, each subsequent trimester, delivery, and at 4, 9, and 12 months after birth. Bivariate analyses were utilized to determine the independent effects of specific drug classes on outcomes. The exposure cohorts were VDZ, UST, TNFs, immunomodulators, and combination with biologics and immunomodulators. All were compared to no exposure to biologics/immunomodulators. Results: There were 1642 completed pregnancies with 1581 live births. Maternal mean age was 32.1±4.6 years at delivery with 62 VDZ and 43 UST exposed. Women on UST were more likely to have Crohn’s disease. There was no increased risk of spontaneous abortion, small for gestational age, low birth weight, neonatal intensive care unit stay, congenital malformations, or intrauterine growth restriction with in utero VDZ or UST exposure (Table). The rate of preterm birth was 0% in UST, 12.7% VDZ, 8.2% TNFs, and 9.7% in the unexposed cohort (p = 0.037). Rates of serious and non-serious infections at birth and within the first 12 months of life were comparable among all groups, with an increase in nonserious infections in VDZ group at 4 months, which did not persist at 1 year. There was no increased risk of placental complications in the VDZ cohort compared to the unexposed cohort. UST infant concentrations at birth were increased whereas VDZ concentrations were overall decreased compared to maternal serum drug concentrations. Conclusion: An updated analysis of UST and VDZ exposure during pregnancy suggests no increase in complications compared to TNFs, immunomodulators and combination of biologics with immunomodulators. UST was associated with lower rates of preterm birth and Cesarean section. No signal was found for increased placental events with either therapy. Continuation of UST and VDZ during pregnancy is recommended. Table 1. - Pregnancy Related Complications by Drug Exposure in completed pregnancies Pregnancy Events(% yes) No exposure(n = 430) Anti-TNFs(n = 700) Immuno-modulators(n = 226) Combination: Biologics + Immunomodulators(n = 179) UST(n = 43) VDZ(n = 62) p-value Any pregnancy complication 86/401(21.4%) 123/649(19.0%) 42/208(20.2%) 28/169(16.6%) 10/39(25.6%) 10/59(16.9%) 0.663 SAB (gestation ages ≤140 days) 9/234(3.8%) 18/438(4.1%) 6/136(4.4%) 2/109(1.8%) 2/21(9.5%) 1/30(3.3%) 0.675 SAB (all gestation ages) 11/429(2.6%) 18/697(2.6%) 7/226(3.1%) 2/178(1.1%) 2/43(4.7%) 1/62(1.6%) 0.739 Preterm birth (< 37 weeks) 38/391(9.7%) 53/643(8.2%) 25/204(12.3%) 24/166(14.5%) 0/38(0.0%) 7/55(12.7%) 0.037 Small for gestational age 16/383(4.2%) 31/579(5.4%) 5/202(2.5%) 3/147(2.0%) 1/14(7.1%) 2/35(5.7%) 0.356 LBW (< 2500 g) 21/380(5.5%) 38/635(6.0%) 9/206(4.4%) 8/159(5.0%) 1/38(2.6%) 6/55(10.9%) 0.493 Intrauterine growth restriction 11/429(2.6%) 13/700(1.9%) 1/226(0.4%) 4/179(2.2%) 0/43(0.0%) 1/62(1.6%) 0.455 Cesarean section 154/394(39.1%) 292/650(44.9%) 93/208(44.7%) 90/168(53.6%) 12/38(31.6%) 26/55(47.3%) 0.024 NICU at birth 58/397(14.6%) 107/651(16.4%) 31/209(14.8%) 29/168(17.3%) 4/37(10.8%) 8/55(14.5%) 0.879 Congenital malformations 28/268(10.4%) 61/581(10.5%) 19/150(12.7%) 18/153(11.8%) 7/39(17.9%) 8/59(13.6%) 0.715 Any of the above 275/430(64.0%) 477/700(68.1%) 156/226(69.0%) 128/179(71.5%) 28/43(65.1%) 42/62(67.7%) 0.513 Abruptio Placenta 3/198(1.5%) 5/302(1.7%) 1/93(1.1%) 1/75(1.3%) 0/13(0.0%) 0/31(0.0%) >0.999 Pre-Eclampsia/Eclampsia 18/198(9.1%) 30/302(9.9%) 13/93(14.0%) 7/75(9.3%) 2/13(15.4%) 4/31(12.9%) 0.512 Placenta previa 5/197(2.5%) 9/302(3.0%) 2/93(2.2%) 1/75(1.3%) 0/13(0.0%) 2/31(6.5%) 0.243 Hemorrhage 5/197(2.5%) 5/302(1.7%) 5/93(5.4%) 2/75(2.7%) 3/13(23.1%) 0/31(0.0%) >0.999 Postpartum hemorrhage 6/197(3.1%) 15/302(2.1%) 1/93(1.1%) 5/75(6.7%) 0/13(0.0%) 1/31(3.2%) >0.999 TNF: tumor necrosis factor, UST: ustekinumab, VDZ: vedolizumab, SAB: spontaneous abortion, LBW: low birth weight, g: grams, NICU: neonatal intensive care unit, vs: versus.