Pharmacokinetics of Certolizumab Pegol in Pregnancy: Results from the Open-Label CHERISH Study

INTRODUCTION: Control of chronic inflammatory diseases (CIDs) during pregnancy is essential for maternal and foetal health; however, the impact of pregnancy on the pharmacokinetics (PK) of CID therapies is unknown. This study investigated the impact of pregnancy on the PK of certolizumab pegol (CZP), a tumour necrosis factor inhibitor (TNFi), in women with CIDs. METHODS: CHERISH (NCT04163016) was a multicentre, longitudinal, open-label phase 1B study evaluating the impact of pregnancy on the PK of CZP in women with CIDs. Pregnant participants on a stable CZP regimen were enrolled at ≤ 10 weeks of gestation. The primary variable was pre-dose and post-dose plasma CZP concentrations throughout pregnancy and postpartum in patients who received ≥ 1 dose. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Of 21 enrolled participants (CZP 200 mg every 2 weeks [Q2W], n = 15; CZP 400 mg Q2W, n = 1; CZP 400 mg Q4W, n = 5), 16 completed the study. Relative to postpartum, pre-dose plasma CZP concentrations were modestly reduced across trimesters 1-3, with no clear pattern in post-dose concentrations. TEAEs occurred in 81.0% of participants, with 'infections and infestations' being most common; only 1 (4.8%) was considered treatment related. Five participants (23.8%) experienced serious TEAEs; none were considered treatment-related. One serious TEAE of foetal death in a high-risk twin pregnancy, one spontaneous abortion was reported in an enrolled participant before their first dose of CZP in the study, and no infant illnesses were reported. CONCLUSIONS: CZP plasma concentrations were modestly lower during pregnancy versus postpartum, were consistent across trimesters, and were within the range observed in studies of non-pregnant individuals with CIDs. Safety was consistent with the established profile of CZP and the patient population. Findings support maintenance of CZP dosing regimens during pregnancy. TRIAL REGISTRATION: ClinicialTrials.gov identifier: NCT04163016.