Pharmacokinetics of Monoclonal Antibodies Throughout Pregnancy: A Systematic Literature Review

Abstract

Background and objective: 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 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available.

Results: A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state.

Conclusion: Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.

Fig. 1

PRISMA 2020 flow diagram for mAbs. mAb monoclonal antibody, PK pharmacokinetics, PRISMA preferred reporting items for systematic reviews and meta-analyses

Fig. 2

The concentration of adalimumab (ADL) during different states of pregnancy. The concentration of ADL is expressed in µg/mL on the y-axis (median with corresponding IQR and range). The different states of pregnancy per study are shown on the x-axis. The different states of pregnancy are expressed as pre-pregnancy (T0), first trimester (T1), second trimester (T2), third trimester (T3), during delivery (T4), and postpartum (T5). FLAa stands for the study of Flanagan et al. (2020); SEO for Seow et al. (2017); LAB for Labetoulle et al. (2019); BOR for Bortlik et al. (2013); JULa for Julsgaard et al. (2013); JULb for Julsgaard et al. (2016); KANa for Kanis et al. (2018); and MAH for Mahadevan et al. (2013) [, , –38]. IQR interquartile range

Fig. 3

The concentration of certolizumab pegol (CZP) during different states of pregnancy. The concentration of CZP is expressed in µg/mL on the y-axis (median with corresponding IQR and range). The different states of pregnancy per study are shown on the x-axis. The different states of pregnancy are expressed as third trimester (T3), during delivery (T4), and postpartum (T5). MOR stands for the study of Morita et al. (2018); MAH for Mahadevan et al. (2013); and MAR for Mariette et al. (2018) [11, 40, 76]. IQR interquartile range

Fig. 4

The concentration of infliximab (IFX) during different states of pregnancy. The concentration of IFX is expressed in µg/mL on the y-axis (median with corresponding IQR and range). The different states of pregnancy per study are shown on the x-axis. The different states of pregnancy are expressed as pre-pregnancy (T0), first trimester (T1), second trimester (T2), third trimester (T3), during delivery (T4), and postpartum (T5). The different colors indicate the stages of pregnancy. FLAa stands for the study of Flanagan et al. (2020); SEO for Seow et al. (2017); STE for Steenholdt et al. (2011); BOR for Bortlik et al. (2013); ELI for Eliesen et al. (2020); JULb for Julsgaard et al. (2016); KANa for Kanis et al. (2018); MAH for Mahadevan et al. (2013); VES for Vestergaard et al. (2017); KANb for Kane et al. (2009); and VAS for Vasilauskas et al. (2006) [11, 12, 14, 29, 33, 35, 36, 38, 43, 45, 47]. IQR interquartile range

Fig. 5

The concentration of natalizumab (NAT) during different stages of pregnancy. The concentration of NAT is expressed in µg/mL on the y-axis (median with corresponding IQR and range). The different states of pregnancy per study are shown on the x-axis. The different states of pregnancy are expressed as pre-pregnancy (T0), first trimester (T1), second trimester (T2), third trimester (T3), during delivery (T4), and postpartum (T5). PRO stands for the study of Proschmann et al. (2021) and TOO for Toorop et al. (2022) [53, 54]. IQR interquartile range

Fig. 6

The concentration of vedolizumab (VDZ) during different stages of pregnancy. The concentration of VDZ is expressed in µg/mL on the y-axis (median with corresponding IQR and range). The different states of pregnancy per study are shown on the x-axis. The different states of pregnancy are expressed as pre-pregnancy (T0), first trimester (T1), second trimester (T2), third trimester (T3), during delivery (T4), and postpartum (T5). FLAa stands for the study of Flanagan et al. (2020); FLAc for Flanagan et al. (2018); JULc for Julsgaard et al. (2018); MITa for Mitrova et al. (2021); MITb for Mitrova et al. (2022); and PRE for Prentice et al. (2023) [, –59]. IQR interquartile range

Fig. 7

The concentration of ustekinumab (UST) during different stages of pregnancy. The concentration of UST is expressed in µg/mL on the y-axis (median with corresponding IQR and range). The different states of pregnancy per study are shown on the x-axis. The different states of pregnancy are expressed as pre-pregnancy (T0), first trimester (T1), second trimester (T2), third trimester (T3), during delivery (T4), and postpartum (T5). FLAb stands for the study of Flanagan et al. (2021); KLE for Klenske et al. (2019); MITa for Mitrova et al. (2021); MITb for Mitrova et al. (2022); PRE for Prentice et al. (2023); ROW for Rowan et al. (2018); SAI for Saito et al. (2022); and SAK for Sako et al. (2021) [, , , –69]. IQR interquartile range