Therapeutic Drug Monitoring of the Biosimilar SB2 (RENFLEXIS™, Infliximab-abda) Using LabCorp Infliximab Assays for Drug Level and Anti-drug Antibodies

Abstract

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX) concentration and anti-infliximab antibody (ADA) titer has helped physicians make informed clinical decisions in the management of inflammatory bowel disease (IBD). A TDM-based approach to treating IBD patients has been used to improve clinical efficacy of anti-TNF agents. The LabCorp IFX TDM test (drug and ADA levels) has been validated in peer-reviewed literature and is widely used by clinicians to help maximize treatment response. Recently approved by the FDA for treatment of IBD, RENFLEXIS (SB2, infliximab-abda) is a biosimilar of the originator infliximab (TNF alpha inhibitor). The aim of this study was to validate the LabCorp IFX TDM test for the quantification of serum SB2 concentrations and ADA. METHODS: To demonstrate ability to measure RENFLEXIS using the LabCorp IFX TDM test, SB2-specific immunoassays were developed. SB2 calibrators and SB2-conjugated key reagents were used to compare with IFX TDM kits. Analytical performance including accuracy, precision, spike and recovery, specificity and selectivity was assessed. Exogenous SB2 was spiked into donor serum to assess recovery using the IFX drug assay. 124 IFX-treated IBD patients were split-tested using SB2 and IFX drug and ADA assays to assess equivalency and interchangeability between the two methods. RESULTS: Both SB2 drug level and ADA showed excellent agreement to IFX drug level and ADA respectively. SB2 assay accuracy (<11% bias) and precision (<7% CV) were equivalent to IFX accuracy (<5% bias) and precision (<10% CV) across the measuring range of the assay. More importantly, spike and recovery of RENFLEXIS using the IFX drug assay was equivalent to the recovery of reference product IFX using the IFX drug assay. SB2 was spiked into the donor serum pool to generate 0.25, 0.5, 1.0, 2.0, 4.0, 5.0, 6.0, & 8.0 ug/mL targets. The same target concentrations were generated for IFX. Both sets of targets were read using the IFX drug assay. Percent recovery of SB2 ranged from 87% to 114%; IFX recovery was 83% to 113%. Average spike and recovery was 99% for both SB2 and IFX using the IFX drug assay. Both the SB2 drug assay and IFX drug assay were used to analyze 59 serum samples of IBD patients treated with reference product IFX. The calculated linear regression between the two methods was Y=1.11x-0.13 and r2=1.0. The SB2-specific anti-drug antibody assay performed essentially identically to the reference product IFX ADA assay in terms of precision (<10% CV), accuracy (<10% bias), linearity, drug tolerance and sensitivity. 65 ADA positive serum samples from IBD patients were tested using the SB2 ADA assay. Antibody titer values were compared. Linear regressions of Y=1.09x-8.7, r2=0.99 were obtained. CONCLUSION(S): This study demonstrates complete cross-reactivity of RENFLEXIS (infliximab-abda) in LabCorp IFX TDM assay. Healthcare providers can confidently use LabCorp IFX TDM test to monitor RENFLEXIS (infliximab-abda) serum drug levels and ADA titers in their patients.