Detection of Anti Infliximab Antibodies in Patients with Inflammatory Bowel Disease (IBD) in the Presence of Infliximab by Homogeneous Liquid Phase Anti Infliximab Mobility Shift Assay

Abstract

Purpose: Trough levels (TL) as well as c-max levels have been positively associated with efficacy and negatively with immunogenicity of infliximab (IFX) in patients with IBD. Degradation of IFX is mainly determined by the presence of anti drug antibodies (ADA), increasing its clearance between 1.4 and 2.7 fold. With evidence accumulating in favour of the concept of therapeutic drug monitoring, standard enzyme linked immunosorbent assays (ELISA) for the detection of ADA reach their limits, as the presence of high IFX levels strongly interferes with the detection of ADA. Here we assess the perfomance of a new assay for the detection of ADA at midinfusion timepoints as compared to samples immediately prior to the next IFX infusion. Methods: 90 consecutive patients with established IBD (66 with Crohn's disease, 24 with Ulcerative Colitis) under maintenance therapy with IFX were asked to participate. Serum samples were acquired at half time between two infusions and immediately prior to the subsequent infusion. IFX drug levels were measured by ELISA (Immundiagnostik, Germany) and ADA were assessed by homogeneous liquid phase anti Infliximab mobility shift assay (HLPA) (Prometheus Labs Inc. CA) for all time points. Results: Patients were receiving a median dose of IFX of 5,51 mg/kg body-weight (4,08-10,94), yielding a median TL of 8.98 yg/ml IFX. Infliximab serum levels were significantly higher at mid infusion versus TL (p=0.000). ADA were detectable in 19 patients and 23 patients at mid infusion and trough timepoints, respectively. 17 patients were concordantly positive, 2 were positive soley at mid infusion and 6 at time of trough sampling. The agreement for the outcome positive ADA measured at week 4 versus week 8 yields a Cohen's kappa of 0,80, with a correlation of t=0,651 (p=0.001). ADA occurred most frequently in patients with non-detectable or very low TL (Table 1).Table: IFX trough levels and presence of ADAConclusion: With HLPA, it is feasible to detect ADA against IFX with excellent accordance not only at low levels of circulating infliximab but also earlier within an infusion interval, when IFX concentrations are high and interfering with conventional ELISAs. ADAs are preferrentially detected in patients with negative or low TLs. Disclosure: The work presented here was supported by Prometheus Labs Inc. who performed the mentioned analyses free of charge. This research was supported by an industry grant from Pormetheus Labs Inc.