Article Text

PDF
PTU-088 Method comparison study of assays for the determination of infliximab, adalimumab, and anti-drug antibody levels in patients with inflammatory bowel diseases
  1. D Nagore1,
  2. A Ruiz del Agua1,
  3. J Pascual1,
  4. F Llinares-Tello2,
  5. B Herreros3,
  6. A Martínez1,
  7. S Martín1,4,
  8. R Navarro5,
  9. L del Rio1
  1. 1R&D, Progenika, Derio
  2. 2Clinical Analysis
  3. 3Digestive Diseases, Hospital Marina Baixa, Villajoyosa
  4. 4Department of Physiology, Medicine and Dentistry School (Zabalduz Scholarship Programme)
  5. 5Department of Physiology, Medicine and Dentistry School, University of the Basque Country UPV/EHU, Leioa, Spain

Abstract

Introduction Several methods are used to measure infliximab (IFX), adalimumab (ADL), antibodies to IFX (ATI) and antibodies to ADL (ATA). These agents elicit an unwanted immune response leading to loss of response. Measurement of drug levels (DL) and anti-drug antibodies (ADA) are often required for routine patient monitoring. The aim of this study was to compare different commercially available ELISA tests for the measurement of DL and ADA for IFX and ADL.

Method A total of 109 samples (69 IFX and 40 ADL) from 71 patients with IBD were included in the study. DL and ADA trough levels were measured with Promonitor kits (Progenika, Spain) and LISA-TRACKER (LT) Duo IFX and ADL kits (Theradiag, France). In addition, drug-spiked samples were analysed to ascertain trueness. Pearson and Bland-Altman analysis was used to study the association and agreement between DL methods. Cohen´s kappa was used to study agreement of ADA assays.

Results Correlation coefficients between each Promonitor test and the corresponding LT assay were 0.99 and 0.83 (p < 0.0001), for IFX and ADL, respectively. Results provided by each DL test were significantly different (p < 0.05): IFX mean±SEM 2.2 ± 0.24 vs 3.4 ± 0.36 mg/L; and ADL 6.0 ± 0.55 vs 4.9 ± 0.39 mg/L for Promonitor and LT, respectively. Analysis of spiked samples indicated that LT make an overestimation and underestimation of IFX and ADL levels, respectively. 23% and 10% of LT measurements were outside the upper limit of quantification (8 mg/L) of each IFX and ADL tests, respectively, and required retesting with higher sample dilutions. All results of Promonitor assays were within the measurement range of the assays (0.035–14.4 mg/L and 0.024–12 mg/L for IFX and ADL, respectively). Analytical sensitivity was similar. In regards to ADA analysis, regardless of the different outputs (assays provide results as arbitrary units and nanograms per millilitre for Promonitor and LT tests, respectively), each pair of tests provided similar qualitative results. Dichotomous analysis with Cohen´s kappa provided values of 0.8 and 1.0 for ATI and ATA, respectively. However, quantification of ATI by LT Duo IFX test was impaired by the limited measurement range of the kit (10–200 ng/mL), with 75% of measurements outside the upper measurement range, which required retesting.

Conclusion Performances of both assays were comparable for all measurements. However, the systematic differences in the magnitude of DL and limited measurement ranges observed for LT tests should be taken with caution since this could impact patient management.

Disclosure of interest D. Nagore Employee of: Progenika, A. Ruiz del Agua Employee of: Progenika, J. Pascual Employee of: Progenika, F. Llinares-Tello: None Declared, B. Herreros: None Declared, A. Martínez Employee of: Progenika, S. Martín Grant/ Research Support from: Progenika, R. Navarro: None Declared, L. del Rio Employee of: Progenika.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.