Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis
Stephanie F. Ling,
Kayode Ogungbenro,
Adam S. Darwich,
Amirah Binti Mohammad Ariff,
Nisha Nair,
James Bluett,
Ann W. Morgan,
John D. Isaacs,
Anthony G. Wilson,
Kimme L. Hyrich,
Anne Barton,
Darren Plant
Affiliations
Stephanie F. Ling
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK
Kayode Ogungbenro
Centre for Applied Pharmacokinetic Research, The University of Manchester, Manchester M13 9PT, UK
Adam S. Darwich
Division of Health Informatics and Logistics, KTH Royal Institute of Technology, 11428 Stockholm, Sweden
Amirah Binti Mohammad Ariff
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK
Nisha Nair
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK
James Bluett
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK
Ann W. Morgan
School of Medicine, University of Leeds, Leeds LS2 9JT, UK
John D. Isaacs
Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne NE1 7RU, UK
Anthony G. Wilson
School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin 4 Belfield, Ireland
Kimme L. Hyrich
NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
Anne Barton
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK
Darren Plant
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK
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.