Abstract
Background and aims
We previously showed a discrepancy between a commercially available enzyme-linked immunosorbent assay (ELISA) and the homogenous mobility shift assay (HMSA) for both infliximab and adalimumab concentrations in patients with inflammatory bowel disease (IBD).1 Based also on the results of this study, Prometheus Laboratories initiated a comprehensive review of their HMSA assays and found that there was an upward drift for both infliximab and adalimumab over a 2-year period, including when our study was being performed. Prometheus corrected the errant values and reported the revised drug concentrations to physicians. We aimed to compare these two assays following the implementation of these corrective measures.
Methods
Samples from patients with IBD either on infliximab or adalimumab maintenance therapy were prospectively evaluated using both ELISA (InformTx™, Inform Diagnostics) (for research purposes) and the HMSA (ANSER™, Prometheus Laboratories) (performed clinically). Comparison of drug concentrations between assays was performed as previously described.1
Results
In total 74 samples were analysed (infliximab, n=45; adalimumab, n=29). Drug concentrations (median [interquartile range, IQR]) were still significantly higher when measured by the HMSA compared to ELISA for foth infliximab (9 [7.1–12.4] vs. 5.7 [4.8–9] μg/ml; p<0.001, respectively) and adalimumab (12.9 [10.3–16.9] vs. 10.6 [8.6–14] μg/ml; p=0.036, respectively). The correlation of infliximab and adalimumab concentrations between assays is depicted in Figure 1. Agreement between assays was moderate [ICC: 0.658; 95% confidence interval (CI): -0.080 to 0.892; p<0.001] for infliximab and strong (ICC = 0.826, 95%CI: -0.066 to 0.949, p<0.001) for adalimumab. A Bland–Altman plot of infliximab and adalimumab concentrations to compare the two assays is shown in Figure 2. Qualitative agreement in drug concentration status (therapeutic or sub-therapeutic) was only minimal between assays using >5 μg/ml (K = 0.299, p=0.005), >7 μg/ml (K = 0.303, p=0.005) or >10 μg/ml (K = 0.323, p=0.003) as therapeutic drug concentrations for infliximab, while for adalimumab was weak using >10 μg/ml as therapeutic drug concentrations (K = 0.437, p=0.004), although overall agreement using either >5 or >7 μg/ml as therapeutic drug concentrations was 97%.
Conclusions
These data suggest that although the correlation between the ELISA and the HMSA was very good for both infliximab and adalimumab it is difficult to compare absolute drug concentrations. Until commercial assays are properly cross-validated and standardized, assay-dependent drug concentration thresholds may need to be applied to better interpret therapeutic drug monitoring results and it is advisable that patients are monitored with the same assay. 1Inflamm Bowel Dis. 2019 Sep 27. https://doi.org/10.1093/ibd/izz202. [Epub ahead of print]
Infliximab and Adalimumab Concentrations May Vary Between the Enzyme-Linked Immunosorbent Assay and the Homogeneous Mobility Shift Assay in Patients With Inflammatory Bowel Disease: A Prospective Cross-Sectional Observational Study