Population Pharmacokinetics of CMAB008 (an Infliximab Biosimilar) and Remicade® in Healthy Subjects and Patients with Moderately to Severely Active Rheumatoid Arthritis

Adv Ther. 2023 Mar;40(3):1005-1018. doi: 10.1007/s12325-022-02396-8. Epub 2023 Jan 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Biosimilar Pharmaceuticals* / therapeutic use
  • Healthy Volunteers
  • Humans
  • Infliximab / therapeutic use
  • Male

Substances

  • Infliximab
  • Biosimilar Pharmaceuticals
  • Antibodies, Monoclonal
  • Albumins
  • Antirheumatic Agents

Associated data

  • ClinicalTrials.gov/NCT04779892
  • ClinicalTrials.gov/NCT03478111