Comparative Study Of Both Versions Of An Immunoassay ...

The fundamental objective of the monitoring of drug therapy is to improve patient care and therapy through dose adjustment based on drug plasma concentrations.10 Therapeutic monitoring of ADA is seen as an essential tool to ensure efficient use of this drug, since clearance differs significantly between individuals and, in time, other factors that can alter its elimination are unknown.11,12 Combined with other clinical data, it provides useful information allowing adjustment of dose in each patient in a guided manner, ensuring optimal therapeutic effect and limiting toxicity.13,14

Several research groups have developed different assay formats for ADA monitoring with their own advantages and disadvantages (ELISA, RIA, cellular assays). But for now, there is no comprehensive comparative study of the various tests which in some cases have shown discrepancies between platforms, highlighting the need for standardization.15

Of all the techniques available, ELISA is the most widely used for its ease of application in clinical practice. The first version of the test evaluated in this study consisted of multiple manual steps and each of them could be the source of analytical variability: from the covering of the wells of the plate to the preparation of calibrators, reagents and samples. In the new version parameters that can induce variability in the results are limited to the maximum: the wells are precovered presented, calibrators and reagents prediluted and sample dilutions restricted for optimal reading.

In the comparative trial a good correlation between measurements of ADA and anti-ADA antibodies with two versions of the test are obtained. In general, V2 provides higher ADA concentration results than V1 and it has a higher accuracy in the range of concentrations near the clinical decision level, being better adjusted to the actual concentration of the drug in blood. In addition, in the new version of the ELISA assay, time is significantly reduced from 6 to 2.5h which allows full automation, greatly simplifying the analysis and significantly reducing the variability in repetitions of the samples something recommended for routine use in the clinical laboratory. Still, we must remember that the test results may be influenced by other difficult to control factors and which may affect the development of any ELISA.

Assuming the inherent limitations of this technique, with the availability of this new commercial version for therapeutic monitoring of ADA, the provision of reliable data for making therapeutic decisions in patients with RA is facilitated. It is necessary to work on the standardization and validation of assays, to reach consensus on the interpretation of drug concentrations and anti-drug antibodies, establishing the therapeutic window for each indication, and treatment algorithms to design evidence-based data validated in clinical practice.