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* = Presenting author

P640 Co-detection of infliximab and antibodies in an ECLIA assay amongst IBD patients treated with infliximab

R. Colman*1, 2, D. Rubin1

1University of Chicago Medicine Inflammatory Bowel Disease Centre, Chicago, Illinois, United States, 2St Barnabas Hospital, Pediatrics, Bronx, New York, United States

Background

Recently an electrochemiluminescence immunoassay (ECLIA) for infliximab (IFX) and antibodies to IFX (ATIs) has become commercially available. While prior research suggests that the ELISA method cannot appropriately detect ATIs in the presence of serum drug levels, less is known about the drug-tolerant ECLIA method. This study assessed the performance characteristics of an ECLIA assay amongst inflammatory bowel disease (IBD) patients treated with infliximab.

Methods

A cross-sectional study was conducted including tests measuring IFX and/or ATIs by ECLIA for IBD patients (from January 2013 to May 2015) at our IBD Centre by Endocrine Sciences, Laboratory Corp of America® Holdings, Calabasas, California, United States. Sensitivity and specificity of ATIs in presence of IFX were calculated by receiver operating characteristic (ROC) curves. To test if this assay accurately detects antibodies, this study considered ATIs in the absence of IFX true positive (TP), and ATIs in the presence of IFX as false positive (FP). In a second ROC analysis, sensitivity and specificity were analysed for IFX with a cut-off of 3.5 μg/mL (the trough level associated with durable sustained response in prior studies of IBD with another immunoassay).

Results

In total, 260 samples (n = 219 patients) were analysed. Further, 36% (94) reported detectable ATI, and of these, IFX levels were present in 77 (29.6%, IFX range (0 [<0.4 μg/mL]–275 μg/mL), ATI range (0 [< 22 ng/mL]– >100,000 ng/mL)). When the assay-defined cut-off of 22 ng/mL for detecting ATIs was used for detecting IFX levels of ≥ 0.4 μg/mL, the ROC curve revealed an area under the curve (AUC) of 0.840 ± 0.058 (95% CI 0.725–0.954, p < 0.0001) with sensitivity to antibody detection of 81% and specificity of 68%, with a positive predictive value (PPV) of 17% (Figure 1).

Figure 1. ROC Curve for ATI and IFX (≥ 0.4 ug/mL).

In the second analysis, when a cut-off of IFX levels of ≥ 3.5 μg/mL was used, the AUC was 0.668 ± 0.044 (95% CI 0.581–0.754, p < 0.0001), with sensitivity of 58% and 70% specificity (PPV = 35%) while using the same cut-off for detecting ATIs (Figure 2).

Figure 2. ROC curve for ATI and IFX (≥ 3.5 ug/mL).

Conclusion

This analysis demonstrates the performance characteristics of the ECLIA assay for IFX and ATI in our tertiary IBD population, and found a high false-positive rate of ATIs. Clinicians should factor these limitations into test selection and clinical management decisions.