P683 Infliximab, adalimumab and vedolizumab levels are not altered by pregnancy progression in IBD patients and neonatal vedolizumab levels are lower than in mothers: Results from the PICCOLO study

Background

Optimal timing for the last intrapartum dose of biologic agents is controversial. We established that cord blood levels of anti-TNF agents in exposed infants are greater than maternal levels,¹ and another study with limited observations suggested maternal infliximab (IFX) levels increased in pregnancy but adalimumab (ADA) levels did not.² The effect of pregnancy on vedolizumab (VDZ) levels, and placental transfer and time to clearance of VDZ in exposed infants remain undefined.

Methods

We performed a prospective observational study of maternal anti-TNF and VDZ levels pre-conception, in each trimester of pregnancy, at delivery and post-partum where possible. Women with IBD on IFX, ADA or VDZ who were pregnant or planning pregnancy were recruited. Serum trough IFX and ADA levels were measured by ELISA (Q-INFLIXI and Q-ADA (Matriks Biotek, Turkey) or Promonitor (Grifols, Spain)) and VDZ levels by ELISA (Theradiag, France). Infant VDZ levels were measured from the umbilical cord at delivery and at around 6–8 weeks and 3 months to assess time to clearance.

Results

Forty-nine patients (24 IFX, 14 ADA, 11 VDZ) with at least two observations on stable dosing were included. The median number of levels per patient was 3 (range 2–5). Infliximab cohort (n = 24): Median IFX levels were stable (Figure 1). IFX was administered 6–8 weekly at doses of 5 mg/kg (n = 21) or 10 mg/kg (n = 2) except for one patient on 4-weekly dosing. The last dose was given at a median 32 weeks; 3 remain pregnant. Adalimumab cohort (n = 14): Median ADA levels were stable (Figure 1). Twelve were on ADA fortnightly and 2 on weekly. Eleven continued ADA throughout pregnancy and 3 stopped at 30–33 weeks; 2 remain pregnant. Three patients were induced in pregnancy at least 12 weeks before the earliest ADA level. Vedolizumab cohort (n = 11): Trough VDZ levels were stable (Figure 2). Eight patients were on 8-weekly dosing and three were on 4-weekly. The last dose was given at a median 30 weeks; 4 remain pregnant (Patients H-K). Vedolizumab in infants (n = 8): The median VDZ cord blood level was 4.95 (1–19) μg/ml with a median infant:maternal ratio of 0.6 (0.4–0.9). VDZ was cleared at 8 weeks of age in three infants and by 15 weeks in two infants.

Figure 1.

Box-plots of trough drug levels before pregnancy (Pre), during each trimester (T1, T2, T3) and post-partum (PP)

Figure 2. Intrapartum and maternal delivery vedolizumab levels