Letter: vedolizumab drug concentrations in neonates following intrauterine exposure

We read with interest the study by Mahadevan et  al regarding the initial experiences of vedolizumab in pregnancy and the subsequent letter by Julsgaard et  al documenting vedolizumab levels in two mother-baby pairs at delivery.1, 2 There remains a paucity of data regarding infant vedolizumab levels and no data regarding time to clearance. We present a case series of five patients with IBD who were treated with vedolizumab during pregnancy and report the maternal vedolizumab levels at delivery, along with corresponding neonatal outcomes including vedolizumab levels. The current study is the first report of time to clearance in infants following intrauterine exposure.

Five women with IBD aged 24-40 years became intentionally pregnant on stable maintenance vedolizumab therapy 300 mg intravenously every 8 weeks following appropriate pre-conception counselling. Four women had failed and/or been intolerant to at least one anti-tumour necrosis factor (TNF) drug, while Patient 4 commenced vedolizumab after ceasing tofacitinib (clinical trial). Three patients remained in remission during pregnancy. Patient 1 elected to stop vedolizumab at 24 weeks as she had been in sustained remission, while Patients 2 and 3 received their last intrapartum doses at 32 weeks and 30 weeks respectively. Patient 4 had planned to cease at 26 weeks, but, due to a mild flare in the third trimester (Mayo 1 disease on flexible sigmoidoscopy) and history of intolerance to steroids, vedolizumab was given at 35 weeks. Patient 5 experienced active disease during pregnancy and had her last dose of vedolizumab at 30 weeks. All five patients delivered healthy babies at term (38-39 weeks) with normal birthweight and normal Apgar scores (Table 1). One infant had hip dysplasia, which resolved; all five infants were otherwise well up to 6 weeks of age.

At the time of delivery, blood samples were taken from the mother and from the umbilical cord to measure vedolizumab concentrations by ELISA (Theradiag LISA TRACKER Duo Vedolizumab, LTV005, Marne La Vallee, France) according to manufacturer's instructions. Infant vedolizumab levels were repeated between 6 and 8 weeks, and at approximately 3 months.

Given that vedolizumab is an IgG1 therapeutic antibody, placental transfer is expected to begin in the second trimester and increase throughout pregnancy.3 Our data show that neonatal levels of vedolizumab are lower than maternal levels at delivery unlike anti-TNF (Table 1). Similar results have been reported in the recent case series by Julsgaard et al and in seven mother-baby pairs from the PIANO registry data.2, 4 There was a negative correlation between days since last intrapartum dose and infant level at delivery (R²=0.62). The vedolizumab levels were undetectable by 6-8 weeks in two infants, and by 15 weeks in one baby (Table 1). In the remaining two babies, further testing was declined.

These results indicate that both placental transfer of vedolizumab and infant time to clearance, respectively, may potentially be less than those documented with anti-TNF monoclonal antibodies. Vedolizumab levels in a larger number of exposed infants are required to more accurately predict clearance. Ongoing case study and registry data remain important to inform appropriate utilisation of vedolizumab in pregnancy.

STATEMENT OF ETHICS

All participants gave written informed consent prior to their inclusion in the study and each participant consented on behalf of their child. Ethics approval was granted through the St Vincent's Hospital Melbourne Ethics Committee (reference number 094/17).