POS0888 PHARMAco*kINETICS OF CERTOLIZUMAB PEGOL IN PREGNANCY: RESULTS FROM THE OPEN-LABEL, PHASE 1B CHERISH STUDY (2024)

Methods: The CHERISH study (NCT04163016) was a multicentre, longitudinal, interventional, prospective, open-label phase 1B exploratory study evaluating the impact of pregnancy on the PK of CZP. The study consisted of a screening period, pregnancy period (up to 40 weeks), post-partum period (up to 13 weeks), and a safety follow-up contact (five weeks after final study visit). Patients (pts) were pregnant (≤10 weeks gestation at time of enrolment) and on stable, maintenance dose CZP treatment for ≥12 weeks prior to being enrolled in the study. Predose PK samples were collected ≤4 hours prior to dosing every 4 weeks (Q4W) starting with the first dose after enrolment. Postdose PK samples were taken 7 days after CZP dose administration every 8 weeks. One predose sample and one postdose sample were taken 11–14 weeks post-partum.

The primary variable was predose and postdose plasma CZP concentrations adjusted for disease phenotype, gestational week, trimester and pre/postdose, assessed in pts receiving ≥1 dose of CZP after enrolment (pharmaco*kinetic per protocol set); safety was assessed in pts receiving CZP at screening (safety set). Adjusted mean differences and 95% confidence intervals were estimated for overall plasma CZP concentrations during pregnancy vs post-partum using a linear mixed effects model.

Results: Of the 21 enrolled pts (CZP 200 mg every two weeks [Q2W], n=15; CZP 400 mg Q2W, n=1; CZP 400 mg Q4W, n=5), 16 (76.2%) completed the study. The mean age of pts was 32.2 (standard deviation: 4.6) years and the most common primary indication for CZP treatment reported was rheumatoid arthritis (n=9 [42.9%]). The range of plasma CZP concentrations observed (Figure 1) was within the range of plasma concentrations observed in CZP studies of non-pregnant pts with PsA, axSpA and rheumatoid arthritis (1.7–45.3 μg/mL).^2,3,4

Plasma CZP concentrations were lower during pregnancy relative to post-partum, though between trimesters there were no large variations in in CZP concentrations. Mean differences in overall plasma CZP concentrations during pregnancy vs post-partum were reduced when accounting for individual serum albumin and body mass index, but not C-‍reactive protein (Figure 2).

The safety profile observed in this study was consistent with the known safety profile of CZP.⁵ 17 (81.0%) pts had a TEAE; the most common maternal TEAE was infections and infestations (n=12 [57.1%]). No study pt deaths, infant illnesses, or other safety concerns were reported.

REFERENCES: [1] Mariette X et al, Ann Rheum Dis 2017;77:228–33. 2. European Medicines Agency, Cimzia Assessment Report 2013; 3. Gehin JE et al, Arthritis Res Ther 2019;21:256. 4. Paul S et al, Clin Transl Sci 2020;13(4):743–51. 5. Curtis JR et al, RMD Open 2019;5(1):e000942.