Introduction: Clearance is the key pharmacokinetic (PK) property of Infliximab (IFX) elimination from the body as a function of time (expressed as L/day) and is a poor prognostic factor associated with immunogenicity, suboptimal exposure and inadequate disease control. Our objective was to compare IFX PK (as clearance) between Originator IFX and Biosimilars.
Methods: De-identified data were extracted from a large commercial database of clinical PK data (Prometheus Laboratories) submitted for Originator (IFX, REMICADE®) or Biosimilars (RENFLEXIS®, IFX-abda and INFLECTRA®, IFX-dyyb) testing. Originator and Biosimilar testing were calibrated against WHO standard (NIBSC code: 16/170) with less than 3% difference in reported levels. Intra-day and inter-day coefficient of variation were below 5% and 10%, respectively. IFX levels, Antibody to IFX (ATI) status ( >3.1 U/mL), dosing and time of specimen collection relative to infusion were analyzed using nonlinear mixed effect models to estimate Clearance. Statistical analysis consisted of Fisher’s exact and Mann-Whitney tests as appropriate.
Results: A total of 9,590 specimens from 7,551 patients (mean age 36 years, 48% female) who received a 5 or 10 mg/Kg q8 weeks dosing schedule were available for this analysis (714 bioequivalent specimens, 66.1% IFX-dyyb and 8,876 Originator). Overall, the PK were comparable between Originator and Biosimilars, although a small trend toward higher Clearance was observed in patients who received Biosimilars as compared to those who received Originator IFX (0.277±0.004 vs 0.262±0.001 L/day, respectively) (p< 0.001). Higher ATI’s were observed with Biosimilars vs Originator (19% [136/714] vs 15% [1320/8876], respectively) (p< 0.001) as well as lower exposure (7.6±0.3 vs 8.5±0.1 µg/mL, respectively) (p< 0.001). These differences were significant only among those who received a 5 mg/Kg q8 weeks schedule. Clearance was 2-fold higher in the presence of ATI and resulted in 6-fold lower exposure for Originator (mean=1.5 vs 9.2 µg/mL) and Biosimilar (mean=1.5 vs 9.7 µg/mL) (p< 0.001).
Discussion: These data suggest that Originator and Biosimilars yield comparable exposure. The small detectable higher immunogenicity rate observed in the group of patients receiving Biosimilars could reflect longer duration of IFX treatment among those who switched from Originator to Biosimilar.
