Point-of-care therapeutic drug monitoring of tumour necrosis factor-α inhibitors using a single step immunoassay

Eva A van Aalen; Ivar R de Vries; Eva T L Hanckmann; Jeannot R F Stevens; Thomas R Romagnoli; Luc J J Derijks; Maarten A C Broeren; Maarten Merkx

doi:10.1039/d3sd00131h

Point-of-care therapeutic drug monitoring of tumour necrosis factor-α inhibitors using a single step immunoassay

Sens Diagn. 2023 Sep 4;2(6):1492-1500. doi: 10.1039/d3sd00131h. eCollection 2023 Nov 9.

Authors

Eva A van Aalen^{1

2}, Ivar R de Vries³, Eva T L Hanckmann^{1

2}, Jeannot R F Stevens^{1

2}, Thomas R Romagnoli^{1

2}, Luc J J Derijks^{4

5}, Maarten A C Broeren⁶, Maarten Merkx^{1

2}

Affiliations

¹ Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology P.O. Box 513 5600 MB Eindhoven The Netherlands m.merkx@tue.nl +31 40 247 4728.
² Institute for Complex Molecular Systems, Eindhoven University of Technology P.O. Box 513 5600 MB Eindhoven The Netherlands.
³ Department of Electrical Engineering, Eindhoven University of Technology P.O. Box 513 5600 MB Eindhoven The Netherlands.
⁴ Department of Clinical Pharmacy and Pharmacology, Máxima Medical Center P.O. Box 7777 5500 MB Veldhoven The Netherlands.
⁵ Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center P.O. Box 5800 6202 AZ Maastricht The Netherlands.
⁶ Laboratory of Clinical Chemistry and Haematology, Máxima Medical Center P.O. Box 7777 5500 MB Veldhoven The Netherlands.

Abstract

Therapeutic drug monitoring (TDM) of tumor necrosis factor-α (TNFα)-inhibitors adalimumab and infliximab is important to establish optimal drug dose and maximize treatment efficacy. Currently, TDM is primarily performed with ELISA techniques in clinical laboratories, resulting in a long sample-to-result workflow. Point-of-care (POC) detection of these therapeutic antibodies could significantly decrease turnaround times and allow for user-friendly home-testing. Here, we adapted the recently developed bioluminescent dRAPPID (dimeric Ratiometric Plug-and-Play Immunodiagnostics) sensor platform to allow POC TDM of infliximab and adalimumab. We applied the two best performing dRAPPID sensors, with limit-of-detections of 1 pM and 17 pM, to measure the infliximab and adalimumab levels in 49 and 40 patient serum samples, respectively. The analytical performance of dRAPPID was benchmarked with commercial ELISAs and yielded Pearson's correlation coefficients of 0.93 and 0.94 for infliximab and adalimumab, respectively. Furthermore, a dedicated bioluminescence reader was fabricated and used as a readout device for the TDM dRAPPID sensors. Subsequently, infliximab and adalimumab patient serum samples were measured with the TDM dRAPPID sensors and bioluminescence reader, yielding Pearson's correlation coefficients of 0.97 and 0.86 for infliximab and adalimumab, respectively, and small proportional differences with ELISA (slope was 0.97 ± 0.09 and 0.96 ± 0.20, respectively). The adalimumab and infliximab dRAPPID sensors, in combination with the dedicated bioluminescence reader, allow for ease-of-use TDM with a fast turnaround time and show potential for POC TDM outside of clinical laboratories.