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Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK;NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.ORCID iD: 0000-0001-8148-2344
Centre for Applied Pharmacokinetic Research, The University of Manchester, Manchester M13 9PT, UK.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.ORCID iD: 0000-0001-8218-4306
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK.
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2024 (English)In: Pharmaceutics, E-ISSN 1999-4923, Vol. 16, no 6, p. 702-702Article in journal (Refereed) Published
Abstract [en]

Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient’s circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy.

Place, publisher, year, edition, pages
MDPI AG , 2024. Vol. 16, no 6, p. 702-702
Keywords [en]
rheumatoid arthritis, pharmacokinetics, population pharmacokinetics, simulation, biologics, biosimilars
National Category
Clinical Medicine
Research subject
Applied and Computational Mathematics
Identifiers
URN: urn:nbn:se:kth:diva-348681DOI: 10.3390/pharmaceutics16060702ISI: 001256552200001Scopus ID: 2-s2.0-85197135723OAI: oai:DiVA.org:kth-348681DiVA, id: diva2:1878186
Note

QC 20240627

Available from: 2024-06-26 Created: 2024-06-26 Last updated: 2025-02-18Bibliographically approved

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Darwich, Adam S.

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