Background Therapeutic drug monitoring of inflammatory bowel disease (IBD) patients under anti-TNF therapy is based on trough level determination of the drug. Rapid assays and multiple ELISAs are available that measure anti-TNF biologics. An international standard is required to improve comparability among different assays. Recently, WHO introduced anti-TNF standards for adalimumab (ADL) and infliximab (IFX). A WHO international reference material (IRM) based standardization is crucial for the harmonization of assays available on the market. Methods The aim of the study was to standardize the BÜHLMANN Quantum Blue® ADL and BÜHLMANN Quantum Blue® IFX based on the WHO IRM for ADL and IFX, respectively. A value transfer from the WHO reference material to the internal calibrator sets for both assays was based on a protocol previously described by Blirup-Jensen et al. (Clin Chem Lab Med 2001; 39(11):1110–1122) and by means of a commercially available ELISA. A method comparison of the ELISA and the rapid test was carried out before the value transfer to guarantee comparability of both assays. Additionally, the correlation of the WHO IRM with the currently used calibrator material was determined for ADL. The correlation of the WHO IFX standard (NIBSC 16/170) with the currently used calibrator material was presented recently (Keller et al. 2020, UEGW 2020). Calibration curves were generated with BÜHLMANN ADL calibrators and with calibrators made from WHO IRM for ADL (NIBSC 17/236). Serum samples, covering a concentration range from 1.0 to 35 µg/mL, were analysed with both calibration curves and compared by Bland-Altman and Passing-Bablok analysis. Results A preliminary value transfer study revealed an relative uncertainty of 12.3% for both drugs. A good comparison of the ADL and IFX rapid test and the ELISA is given: Passing-Bablok correlation coefficient (R) of 0.953 (ADL) and 0.942 (IFX), and a mean bias determined by Bland-Altman of 1.59 µg/mL (ADL) and -0.5 µg/mL (IFX), respectively. The sample values gained with BÜHLMANN calibrators showed an excellent correlation with values gained with the WHO international standard for ADL as calibrator. Passing-Bablok regression analysis revealed a slope of 1.3 and correlation coefficient (R) of 1.0. Conclusion To the best of our knowledge, the Quantum Blue® ADL and Quantum Blue® IFX, are the first commercially available quantitative lateral flow assays comprising a WHO based standardization. Additionally, it was demonstrated that the current standardizations of Quantum Blue® ADL correlates very well with the WHO international standard for ADL.
Background Patients suffering from inflammatory bowel disease can be treated with the biologics adalimumab (ADL) or infliximab (IFX). Previous studies demonstrated the usefulness of therapeutic drug monitoring (TDM) to adjust the patient’s biologic concentration individually. Commercially available rapid assays support laboratories in the fast and easy detection of ADL and IFX concentrations but the assays’ dependency on serum as analyte matrix is a general hindrance for TDM, as serum preparation from whole blood is time-consuming and requires laboratory equipment. Patients and clinicians would thus benefit from rapid point-of-care (POC) and easy to use assays that are independent of laboratory equipment. The objective of this project was to expand existing serum lateral flow assays for the analysis of ADL or IFX in capillary blood and investigate potential interactions resulting from the blood matrix. Methods ADL and IFX lateral flow serum kits were optimized in such a way that both, capillary blood and EDTA whole blood can be used as analyte matrix by using disposable capillaries for blood collection and for its transfer into dropper bottles that are prefilled with chase buffer. To measure ADL or IFX levels with a POC lateral flow test cassette reader (BÜHLMANN Quantum Blue® Reader) the mixture is then applied on an ADL or IFX lateral flow test cassette. Matrix agreement studies were performed to compare spiked EDTA whole blood and capillary blood samples with serum as reference. Additionally, spiked EDTA whole blood samples were treated to obtain three abnormal blood conditions: Icteric, hemolytic and lipemic blood. Bias in results exceeding 30% relative difference to the untreated sample was considered as an interference. Results Spiked blood samples showed good agreement with reference serum samples. A bias of less than 15% at the clinical decision points for ADL (5 µg/mL and 12 µg/mL) and IFX (3 µg/mL and 7 µg/mL) was revealed. Observed relative differences between all tested abnormal blood conditions ranged between -20% and +26% for IFX and -16% and +5% for ADL. Conclusion Two POC assays for the determination of ADL or IFX in capillary blood or EDTA whole blood samples were successfully developed and can be used by healthcare professionals with time to results of only 15 minutes and without the need for additional laboratory equipment. No systematic interferences were detected with treated EDTA whole blood samples, which could appear when using blood as analyte matrix. The excellent agreement to serum trough levels shows that the POC adalimumab/infliximab capillary blood assays are ideal for therapeutic drug monitoring analysis at a clinician’s office or an infusion site.
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