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Comparative Study
. 2017 Nov;83(11):2474-2484.
doi: 10.1111/bcp.13371. Epub 2017 Aug 22.

Dried Blood Spots From Finger Prick Facilitate Therapeutic Drug Monitoring of Adalimumab and Anti-Adalimumab in Patients With Inflammatory Diseases

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Free PMC article
Comparative Study

Dried Blood Spots From Finger Prick Facilitate Therapeutic Drug Monitoring of Adalimumab and Anti-Adalimumab in Patients With Inflammatory Diseases

Eva L Kneepkens et al. Br J Clin Pharmacol. .
Free PMC article

Abstract

Aims: Development of a self-sampling method for therapeutic drug monitoring (TDM) of biologicals will enhance TDM implementation in routine care and pharmacokinetic knowledge. The aim of this study was to compare adalimumab and anti-adalimumab antibody (ADA) concentration measurements in dried blood spots (DBS) obtained from finger prick with measurements in serum obtained via venepuncture, from patients with rheumatic inflammatory diseases.

Methods: In this cross-sectional study, 161 consecutive patients were included. For clinical validation, DBS from finger prick and serum from venepuncture were collected simultaneously and adalimumab and ADA concentration were assessed by ELISA and antigen binding test (ABT), respectively. To convert DBS eluate results to values which can be compared to serum concentrations, five different methods were investigated, using a marker protein or a volumetric approach.

Results: Adalimumab and ADA concentrations obtained from the finger prick/DBS method correlated well with serum results from the same patient (correlation coefficient > 0.87). Interestingly, antibody concentrations (either adalimumab, ADA or total immunoglobulin G) in DBS from finger prick, but not albumin, were systematically lower compared to serum. Spike experiments demonstrated a quantitative recovery for all tested proteins in DBS, suggesting a slightly different protein composition of blood collected via finger prick vs. venepuncture. We established a correction factor to relate finger prick/DBS values with serum values (approximately 1.2).

Conclusions: We show here for the first time that adalimumab and ADA serum concentrations can be satisfactorily estimated by measuring concentrations in DBS eluates, collected by finger prick. This method offers great opportunity to simplify TDM of adalimumab.

Keywords: adalimumab; dried blood spot; finger prick; immunogenicity; rheumatic diseases.

Figures

Figure 1
Figure 1
Correlation of adalimumab (ADL) (mg l−1) (A) and anti‐ADL (AU ml−1) (B) measured in Vp‐serum as reference value vs. the DBS‐serum concentration calculated with the DBS H0.42 method. Data were analysed with Spearman correlation and Deming regression. ADL: r = 0.9342; slope (95% confidence interval (CI)): 0.8160 (0.774–0.8580); intercept (95% CI): 0.0722 (−0.2419–0.3864); anti‐ADL: r = 0.8741; slope (95% CI): 0.8488 (0.8416–0.8560); intercept (95% CI): −2.05 ± (−34.65–30.55); four DBS‐serum concentrations were low positive (13.3–17.1 AU ml−1) whereas antibodies were not detected above the cut‐off of 12 AU ml−1 in the corresponding sera
Figure 2
Figure 2
Percentage deviation ( DBSserumVpserumVpserum100%) in adalimumab (ADL) concentration (mg l−1) calculated from the DBS eluates in the five different ways (DBS‐serum concentrations) compared to the corresponding Vp‐serum concentrations as reference value. The dashed line represents the median deviation, the dotted lines represent the ±1.96 SD of the mean. The mean, % coefficient of variation (CV), estimated %CV and 95% CI of the median are given in the embedded box
Figure 3
Figure 3
Percentage deviation in adalimumab (ADL) concentration (mg l−1) calculated from the DBS eluates with the diagnostic method DBS H0.42 compared to the corresponding Vp‐serum concentration plotted against the quartiles of the ADL concentration (mg l−1) (A) or the Hct values (l l−1) (B). Box plots with minimum to maximum deviation are shown. Data were analysed with a Kruskal–Wallis test and no significant differences (P < 0.05) between the different quartiles were found
Figure 4
Figure 4
Percentage deviation in IgG concentration (g l−1) calculated from the DBS eluates with the diagnostic method DBS H0.42 compared to the corresponding Vp‐serum concentration plotted against the Vp‐serum IgG concentration. One outlier in percentage deviation in IgG concentration was identified by Grubbs analysis (black triangle) and removed from the data set. The dashed line represents the median deviation, the dotted lines represent the ±1.96 SD of the mean (A). Percentage deviation in albumin concentration (g l−1) calculated from the DBS eluates with the diagnostic method DBS H0.42 compared to the corresponding Vp‐serum concentration plotted against the Vp‐serum albumin concentration. The dashed line represents the median deviation, the dotted lines represent the ±1.96 SD of the mean (B). Adalimumab (ADL) spiked Vp‐blood was spotted on DBS cards; eluates were made and ADL, IgG and albumin concentrations were measured. The DBS‐plasma concentration was calculated based on the spotted amount of blood in combination with the measured Hct value. DBS‐plasma concentration is presented as percentage recovery compared to Vp‐plasma concentration (C)

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