PII-135 - PHARMACOKINETICS OF MONOCLONAL ANTIBODIES THROUGHOUT PREGNANCY: A SYSTEMATIC LITERATURE REVIEW

J. van Gendt¹, R. Emaus¹, M. Visschedijk², D. Touw¹, D. Bouwknegt³, K. de Leeuw⁴, J. Prins⁵, P. Malik⁶, P. Mian¹; ¹Clinical Pharmacy and Pharmacology, ²gastroenterology, ³Gastroenterolgy, ⁴rheumatology, ⁵gynaecology, ⁶Calico Life Sciences.

Background: Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy.

Methods: A systematic literature search was carried out in PubMed and Embase on 21st April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available.

Results: A total of 33 relevant articles were included, of which eight discussed adalimumab (ADL), three certolizumab pegol (CZP), one golimumab (GOL), twelve infliximab (IFX), four eculizumab (ECU), two natalizumab (NAT), three tocilizumab (TCZ), five vedolizumab (VDZ) and five ustekinumab (UST). One of the 33 studies reported information on clearance and volume of distribution of IFX; all other studies only reported on serum concentrations in pre-pregnancy state, different trimesters and in the post-partum period. When administering a flat dose (all mAbs except IFX), serum concentrations of mAbs were similar or decreased throughout pregnancy. When administering a dose based on total body weight (mg/kg, IFX), serum concentrations generally increased throughout pregnancy.

Conclusion: Available information suggests that the anatomical and physiologic changes throughout pregnancy may have meaningful effects on the PK of mAbs. Modestly higher flat doses may be needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy. However, increasing the dose in proportion to total body weight would result in over-exposure.