Introduction: CMAB008 is a monoclonal antibody developed as a biosimilar to infliximab (Remicade®, Janssen). The pharmacokinetic characteristics of CMAB008 and Remicade® in healthy subjects and patients with moderately to severely active rheumatoid arthritis (RA) were investigated using a population modeling approach, and the pharmacokinetic similarity of CMAB008 to Remicade® was assessed.
Methods: The population pharmacokinetic model was developed on the basis of intensive pharmacokinetic data from a phase 1 study in healthy male subjects and combined intensive and sparse pharmacokinetic data from a phase 3 study in patients with RA.
Results: A two-compartment model with first-order elimination adequately described CMAB008 and Remicade® concentration data in healthy subjects and patients with RA. The analysis of covariates identified anti-drug antibody (ADA), neutralizing antibody (NAB), real-time body weight (BWT), and real-time albumin (ALB) as significant covariates on clearance, and BWT was also a significant covariate for the central volume of distribution. The treatment type (CMAB008 versus Remicade®) and the study population (healthy subjects versus patients with RA) were not identified as significant covariates on the pharmacokinetics of infliximab, demonstrating pharmacokinetic similarity between CMAB008 and Remicade® in both study populations. The effect of BWT and ALB changes on exposures to infliximab was within the acceptable range, suggesting that the 3 mg/kg regimen is appropriate in clinical practice for patients with RA and BTW and ALB distribution within the range evaluated in the current analysis.
Conclusions: The pharmacokinetic characteristics were similar between CMAB008 and Remicade® in healthy subjects and patients with RA. CMAB008 can be considered bioequivalent to Remicade®.
Clinical trial registration: ClinicalTrials.gov identifiers NCT04779892, NCT03478111.
Keywords: Biosimilar; Infliximab; Population pharmacokinetic; Rheumatoid arthritis.
© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.