B-340 Performance of a Quality System for Targeted Monoclonal Antibodies in a Reference Clinical Pharmacokinetic Laboratory

Abstract

Abstract Background The homogenous mobility shift assay (HMSA) laboratory developed test (LDT) quantifies monoclonal antibody drug and anti-drug antibody levels and is useful for the management of inflammatory bowel diseases (IBD). We report the implementation and performance of a quality system for these LDTs, as well as longitudinal trends of exposure and immunization prevalence from a reference clinical pharmacokinetic (PK) laboratory (Prometheus Laboratories, Inc.). Methods Quality control (QC) HMSA data was evaluated to verify conformance to specifications for infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST) and their respective anti-drug antibodies (antibody to IFX [ATI], ADA [ATA], VDZ [ATV], and UST [ATU]). A QC panel consisting of five serum specimens spanning the reportable range per each drug or anti-drug antibody LDT was established, stored at subzero temperature, and tested monthly over a period of two years. Acceptable performance consisted of 80%–120% accuracy from the target value. All specimens were blinded to operator and processed with the clinical PK load of testing. Exposure and immunization prevalence over three years of testing was evaluated. All patient data were de-identified before analysis. Median drug level (interquartile ranges [IQR]), and anti-drug percent positivity by international classification of disease was also estimated (ICD-10 based). Results The QC results establish that the drug (IFX, ADA, VDZ, UST) and anti-drug (ATI, ATA, ATV, ATU) LDTs report acceptable performance with 80%–120% accuracy over the two-year evaluation period. Median drug concentrations with IQR were assessed for the clinical sample set differentiated by disease classification as depicted in Fig. 1. Anti-drug positivity levels were higher for ATI (mean: 11.5%) and ATA (mean: 13.6%) than those from ATV (mean 2.0%) and ATU (mean: 0.6%). Conclusion The QC data presented supports the performance of HMSA for therapeutic drug monitoring (TDM) of IBD and other immune mediated inflammatory diseases.