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P241 Advantages of a fully automated chemiluminescent method for therapeutic drug monitoring (TDM) of anti-TNFα in patients with Inflammatory Bowel Diseases

Cifù, A.(1);Marino, M.(2);Sablich, R.(3);Carletti, M.(4);Blasone, N.(4);Milloch, S.(4);Curcio, F.(1);Fabris, M.(4);

(1)University of Udine, Department of Medicine DAME, Udine, Italy;(2)Azienda Sanitaria Universitaria Friuli Centrale ASUFC, Clinic of Gastroenterology, Udine, Italy;(3)Azienda Sanitaria Friuli Orientale ASFO, Clinic of Gastroenterology, Pordenone, Italy;(4)Azienda Sanitaria Universitaria Friuli Centrale ASUFC, Institute of Clinical Pathology, Udine, Italy;

Background

In recent decades, biological drugs targeting anti-tumour necrosis factor-α (TNF-α) have represented the cornerstone in the treatment of inflammatory bowel diseases. Currently, anti- TNF-α represents a breakthrough in patient care. However, 20-50% of patients experience primary or secondary loss of response. This may be due to pharmacodynamic and/or pharmacokinetic issues, resulting in subtherapeutic drug concentrations, frequently related to the development of anti-drug antibodies (ADA).

In this context, therapeutic drug monitoring (TDM) is essential to patients’ management in order to pinpoint the basis of reduced efficacy. Indeed, a fast and reliable assessments of TDM is mandatory to allow rapid intervention, to avoid toxicity and improve treatment efficacy.

In this study we assess the analytical performance of a novel fully automated chemiluminescent assay in measuring biological drugs levels and ADA serum concentration and to compare its performances to the current diagnostic method (ELISA).

Methods

Serum levels of biological drugs (Infliximab and Adalimumab) and their respective ADA were measured in twenty infliximab (IFX)-treated IBD patients and twenty adalimumab (ADL)-treated IBD patients using both the Promonitor® ELISA kits (Grifols) and the i-TRACKER chemiluminescent (CLIA) kits (Theradiag

Results

The CLIA method is a random-access platform that allows the continuous loading of samples, while the ELISA is a time-consuming manual method to be planned in advance to reduce expenses. Actually, in our laboratory is performed only twice a month. A very good correlation was observed both for Infliximab (Spearman r=0.9695, 95%CI = 0,92-0,99, p<0.0001) and Adalimumab serum levels (Spearman r=0.9476, 95%CI = 0,86-0,98, p<0.0001). Among the patients with undetectable IFX serum levels, 6/8 (75%) resulted ADA positive by ELISA versus 8/8 (100%) by CLIA. Moreover, CLIA disclosed very high ADA concentration in 3 samples compared to borderline results by ELISA. Regarding ADL, all the 9 patients with undetectable serum levels presented similar ADA concentration as tested with ELISA or CLIA.

Conclusion

In conclusion, the i-TRACKER CLIA Infliximab and Adalimumab assays showed a very good correlation for serum-based drugs level quantification as compared to the related ELISA methods. Furthermore, a good agreement was observed for ADA analysis, with a higher sensitivity against anti-IFX antibodies by CLIA compared to ELISA. Our data clearly highlighted that a fully automated assay for TDM would certainly reduce costs and significantly improve the management of IBD patients in terms of a shorter turn-around time.

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