Infliximab Assay Used in Clinical Practice Validated for Measuring SB2 Infliximab Biosimilarʼs Serum Drug and Anti-drug Antibody Levels

Abstract

Introduction: Study aimed to validate suitability of assays from THERADIAG (available in US via Miraca Life Sciences as InformTXTM, promoted as LISA-TRACKER (LT) outside of US) for monitoring of patients treated with Infliximab (IFX) biosimilar developed by Samsung Bioepis (SB2). LT has been developed to quantify IFX and Anti-IFX antibodies (Ab) in human serum/plasma for monitoring of patients treated with originator IFX (Remicade®). Methods: For IFX quantification, recombinant human TNFa on solid phase was used to catch IFX, and biotinylated anti-human-IgG for the detection step. For Anti-IFX quantification, IFX was coated on solid phase, and biotinylated IFX was used for the detection step. For both assays, conjugate and substrate were used before the reading of optical density (OD). Level of IFX or Anti-IFX was proportional to OD. 2 batches of SB2 were assessed. 3 human serum matrix were used to prepare spiked samples. 58clinical samples were collected from US patients treated with originator IFX. Inhibition assays were performed in using polyclonal Ab. Results:IFX ASSAY:SB2 spiked samples gave % of recovery between 81% and 105%. Coefficients of variation ranged from 2.2% to 10.3% for intra-run and from 4.4% to 12.7% for inter-run precision assay. Clinical samples with detectable levels of IFX spiked with SB2 or originator IFX gave similar results. IFX assay gave consistent results even if SB2 is quantified after storage of samples during 7 days at +2°C+8°C, or 3 days at room temperature, or after 5 freeze/thaw cycles. ANTI-IFX ASSAY:All clinical samples with a detectable level of Anti-IFX Ab were inhibited when originator IFX or SB2 were added to the samples. SB2 has the capacity to block detection of Anti-IFX Ab when added to detection reagent. Very good correlation was obtained when originator IFX or SB2 were used for reagents production: R2>0.97; 0.91 Conclusion: LT IFX assay gave high precision and accuracy for quantification of SB2. Behavior of SB2 and originator IFX in tested LT assays is similar. Results indicate that Anti-IFX Ab induced by SB2 should be detected with LT Anti-IFX assay. InformTXTM, or LT, are suitable for monitoring of patients treated with SB2. Study demonstrated that the assay can be used interchangeably for monitoring drug level and Anti-IFX for originator IFX and SB2.