Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases
Abstract Certolizumab pegol (CZP; CIMZIA™) is the only Fc‐free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases w...
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| Format: | Article |
| Language: | English |
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Wiley
2024-11-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13220 |
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| author | Denis Menshykau Jagdev Sidhu Laura Shaughnessy Rocio Lledo‐Garcia Pinky Dua Marie Teil Akash Khandelwal |
| author_facet | Denis Menshykau Jagdev Sidhu Laura Shaughnessy Rocio Lledo‐Garcia Pinky Dua Marie Teil Akash Khandelwal |
| author_sort | Denis Menshykau |
| collection | DOAJ |
| description | Abstract Certolizumab pegol (CZP; CIMZIA™) is the only Fc‐free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases were assessed using a population PK model based on data from the CHERISH study (NCT04163016), a longitudinal, prospective, open‐label PK phase IB study. Model development was performed in NONMEM using a frequentist prior approach, with prior information based on a population PK model for certolizumab pegol in non‐pregnant adult patients (NCT04740814). A one‐compartment model with first‐order absorption (Ka = 0.236 1/day) and linear elimination (CL/F = 0.416 L/day) from the central compartment (V/F = 7.86 L) best described certolizumab pegol PK in the CHERISH study. The structural model parameters were estimated with good precision (RSE < 25%). Baseline BW was included as a covariate on CL/F and V/F. Pregnancy trimester and time‐varying log‐transformed anti‐drug antibody (ADA) titer were identified as the only significant covariates for CL/F with a comparable influence on CL/F. Individuals with higher ADA titer (75th percentile) during pregnancy exhibited CL/F up to 1.43‐fold higher relative to individuals postpartum that showed median levels of ADA titer. However, the confidence interval for the combined effect of pregnancy stage and ADA titer effects on CL/F overlapped with the CL/F range of the typical individual postpartum. In addition, simulations showed a large overlap in certolizumab pegol concentrations between pregnant and non‐pregnant adults. The findings of this population PK analysis support the maintenance of established certolizumab pegol dosing regimens throughout pregnancy. |
| format | Article |
| id | doaj-art-0ea6f96c831248acb8c94d0a71f46dd0 |
| institution | Kabale University |
| issn | 2163-8306 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj-art-0ea6f96c831248acb8c94d0a71f46dd02024-11-20T17:18:44ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062024-11-0113111904191410.1002/psp4.13220Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseasesDenis Menshykau0Jagdev Sidhu1Laura Shaughnessy2Rocio Lledo‐Garcia3Pinky Dua4Marie Teil5Akash Khandelwal6UCB Biosciences GmbH Monheim am Rhein GermanyUCB Australia Pty Ltd Malvern Victoria AustraliaUCB BioSciences Inc Raleigh North Carolina USAUCB Pharma Slough UKUCB Pharma Slough UKUCB Biopharma SRL Brussels BelgiumUCB Biosciences GmbH Monheim am Rhein GermanyAbstract Certolizumab pegol (CZP; CIMZIA™) is the only Fc‐free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases were assessed using a population PK model based on data from the CHERISH study (NCT04163016), a longitudinal, prospective, open‐label PK phase IB study. Model development was performed in NONMEM using a frequentist prior approach, with prior information based on a population PK model for certolizumab pegol in non‐pregnant adult patients (NCT04740814). A one‐compartment model with first‐order absorption (Ka = 0.236 1/day) and linear elimination (CL/F = 0.416 L/day) from the central compartment (V/F = 7.86 L) best described certolizumab pegol PK in the CHERISH study. The structural model parameters were estimated with good precision (RSE < 25%). Baseline BW was included as a covariate on CL/F and V/F. Pregnancy trimester and time‐varying log‐transformed anti‐drug antibody (ADA) titer were identified as the only significant covariates for CL/F with a comparable influence on CL/F. Individuals with higher ADA titer (75th percentile) during pregnancy exhibited CL/F up to 1.43‐fold higher relative to individuals postpartum that showed median levels of ADA titer. However, the confidence interval for the combined effect of pregnancy stage and ADA titer effects on CL/F overlapped with the CL/F range of the typical individual postpartum. In addition, simulations showed a large overlap in certolizumab pegol concentrations between pregnant and non‐pregnant adults. The findings of this population PK analysis support the maintenance of established certolizumab pegol dosing regimens throughout pregnancy.https://doi.org/10.1002/psp4.13220 |
| spellingShingle | Denis Menshykau Jagdev Sidhu Laura Shaughnessy Rocio Lledo‐Garcia Pinky Dua Marie Teil Akash Khandelwal Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases CPT: Pharmacometrics & Systems Pharmacology |
| title | Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases |
| title_full | Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases |
| title_fullStr | Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases |
| title_full_unstemmed | Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases |
| title_short | Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases |
| title_sort | population pk modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases |
| url | https://doi.org/10.1002/psp4.13220 |
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