Oral Presentation Australasian Diabetes in Pregnancy Society and Society of Obstetric Medicine Australia and New Zealand Joint Scientific Meeting 2021

Ustekinumab levels in pregnant women with Inflammatory Bowel Disease and neonates exposed in-utero (#33)

Ralley Prentice 1 2 3 , Emma Flanagan 4 5 , Alyson Ross 4 , Peter R Gibson 3 6 , Ourania Rosella 3 , Katerina V Kilburg 5 7 , Emily K Wright 4 5 , Sally Bell 1 3 5
  1. Department of Gastroenterology, Monash Health, Clayton, VIC, Australia
  2. Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, VIC
  3. Monash University, Melbourne, VIC
  4. Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia
  5. University of Melbourne, Melbourne, VIC
  6. Department of Gastroenterology, Alfred Health, Melbourne, VIC
  7. Department of General Medicine, St Vincent's Hospital Melbourne, Melbourne, VIC

Introduction: Ustekinumab (UST) is increasingly used in the management of inflammatory bowel disease (IBD). While UST use during pregnancy is likely to be safe(1, 2), pharmacokinetic data in pregnancy and in exposed infants are limited (1, 3, 4).

Aims/Methods: The aim was to establish the stability of UST levels antenatally, the ratio of infant to maternal UST levels at delivery and the time to clearance from the infant. Women receiving UST for IBD prior to conception or when pregnant were prospectively recruited. Maternal trough UST levels were measured in each trimester and at delivery where possible. Infant UST levels were measured from the umbilical cord at delivery and repeated between 6–9 weeks of age. In infants with detectable UST levels further testing was performed to determine time to clearance.  UST levels were measured by ELISA (Theradiag).

Results: Ten participants, all with Crohn’s disease, with at least two antenatal or matched infant/maternal delivery UST levels were receiving UST every 8 weeks in 7, 6 weeks in 1 and 4 weeks in 2. All were in clinical remission, but 2 had biochemical evidence of disease activity. No babies were born prematurely, with a median gestational age of 38.5 weeks (IQR 38.0-39.0). The birthweight was 3246 (2810-3480)g. One minor congenital heart defect was noted. Trough UST levels (µg/ml) were 2.3 (range 1.3-2.4) in trimester 1 (n=3), 2.2 (IQR 1.6-2.3) in trimester 2 (n=7) and 1.8 (1.6-3.3) in trimester 3 (n=4), with no significant difference over the course of pregnancy (p = 0.29) (Figure 1). Infant and non-trough maternal UST levels (µg/ml) at delivery were 4.0 (1.2-7.8) and 1.4  (0.7-4.4) respectively (n=10), with an infant:maternal ratio of 1.8 (1.4-2.6). There was a positive correlation between maternal and infant delivery levels (R= 0.76, p= 0.01). There was an inverse correlation between the number of weeks from final antenatal dose to delivery and infant UST delivery level (R = -0.84, p<0.01). 6/10 infants had follow up UST levels performed. Median time of infant UST clearance was 9 (range 8-19) weeks (n=5), clearance time being longer if UST was administered in the third trimester (n=3).

Conclusions: UST levels are stable in pregnancy. The infant:maternal ratio at birth was similar to that seen with anti-TNFs, but higher than for vedolizumab. Infants exposed in third trimester should avoid live vaccination before six months of age.

 

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Figure 1. Individual and median UST trough levels across pregnancy