Background: PF-06438179/GP1111 (PF-SZ-IFX) is an infliximab (IFX) biosimilar. Pharmacokinetic (PK) similarity of PF-SZ-IFX and reference IFX authorized in the European Union (ref-IFX-EU) and in the US (ref-IFX-US) was demonstrated in healthy subjects. Safety and efficacy of PF-SZ-IFX were investigated in a multinational, double-blind, randomized study in rheumatoid arthritis (RA) patients. This work aims to evaluate the population pharmacokinetics (PopPK) of ref-IFX-EU and PF-SZ-IFX in RA patients. Research design and methods: Patients with moderately to severely active RA (N = 650) were randomized 1:1 to PF-SZ-IFX or ref-IFX-EU. PopPK modeling with data collected from the study was performed using a nonlinear mixed-effects approach (NONMEM 7.2.0). Results: The PK of ref-IFX-EU and PF-SZ-IFX were adequately described using a two-compartment model with linear elimination. Clearance (CL) estimates were 0.014 L/h and 0.015 L/h for PF-SZ-IFX and ref-IFX-EU, with inter-individual variability (IIV) on CL of 43.1% and 40.1%, respectively. Volumes of distribution in the central compartment (V1) were 3.38 L and 3.57 L, with IIV on V1 of 28.1% and 23.7%, respectively. The same covariates of sex and antidrug antibody titers on CL, and body weight on V1, influenced the PK variability of ref-IFX-EU and PF-SZ-IFX. Conclusions: PopPK analysis revealed no appreciable differences between the PK of ref-IFX-EU and PF-SZ-IFX in RA patients. Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02222493).
Keywords: Biosimilar; NONMEM; PopPK; infliximab; pharmacokinetics; rheumatoid arthritis.