Dried Blood Spots from Finger Prick Facilitate Therapeutic Drug Monitoring of Adalimumab and Anti-adalimumab in Patients with Inflammatory Diseases

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2017 Aug 10

PMID 28791718

Citations 16

Authors

Eva L Kneepkens

Mieke F Pouw

Gerrit Jan Wolbink

Tiny Schaap

Michael T Nurmohamed

Annick de Vries

Theo Rispens

Karien Bloem

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Garces S, Antunes M, Benito-Garcia E, da Silva J, Aarden L, Demengeot J . A preliminary algorithm introducing immunogenicity assessment in the management of patients with RA receiving tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2013; 73(6):1138-43. DOI: 10.1136/annrheumdis-2013-203296. View

Lehmann S, Delaby C, Vialaret J, Ducos J, Hirtz C . Current and future use of "dried blood spot" analyses in clinical chemistry. Clin Chem Lab Med. 2013; 51(10):1897-909. DOI: 10.1515/cclm-2013-0228. View

Pouw M, Krieckaert C, Nurmohamed M, van der Kleij D, Aarden L, Rispens T . Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis. 2013; 74(3):513-8. DOI: 10.1136/annrheumdis-2013-204172. View

van Schouwenburg P, Bartelds G, Hart M, Aarden L, Wolbink G, Wouters D . A novel method for the detection of antibodies to adalimumab in the presence of drug reveals "hidden" immunogenicity in rheumatoid arthritis patients. J Immunol Methods. 2010; 362(1-2):82-8. DOI: 10.1016/j.jim.2010.09.005. View

Kneepkens E, Cheng-Chung Wei J, Nurmohamed M, Yeo K, Chen C, van der Horst-Bruinsma I . Immunogenicity, adalimumab levels and clinical response in ankylosing spondylitis patients during 24 weeks of follow-up. Ann Rheum Dis. 2013; 74(2):396-401. DOI: 10.1136/annrheumdis-2013-204185. View

Vogelzang E, Kneepkens E, Nurmohamed M, van Kuijk A, Rispens T, Wolbink G . Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up. Ann Rheum Dis. 2014; 73(12):2178-82. DOI: 10.1136/annrheumdis-2014-205554. View

Capiau S, Stove V, Lambert W, Stove C . Prediction of the hematocrit of dried blood spots via potassium measurement on a routine clinical chemistry analyzer. Anal Chem. 2012; 85(1):404-10. DOI: 10.1021/ac303014b. View

Krieckaert C, Rispens T, Wolbink G . Immunogenicity of biological therapeutics: from assay to patient. Curr Opin Rheumatol. 2012; 24(3):306-11. DOI: 10.1097/BOR.0b013e3283521c4e. View

Timmerman P, White S, Cobb Z, de Vries R, Thomas E, van Baar B . Update of the EBF recommendation for the use of DBS in regulated bioanalysis integrating the conclusions from the EBF DBS-microsampling consortium. Bioanalysis. 2013; 5(17):2129-36. DOI: 10.4155/bio.13.173. View

10.

Coates L, Helliwell P . Validation of minimal disease activity criteria for psoriatic arthritis using interventional trial data. Arthritis Care Res (Hoboken). 2010; 62(7):965-9. DOI: 10.1002/acr.20155. View

11.

Girish V, Vijayalakshmi A . Affordable image analysis using NIH Image/ImageJ. Indian J Cancer. 2004; 41(1):47. View

12.

Timmerman P, White S, Globig S, Ludtke S, Brunet L, Smeraglia J . EBF recommendation on the validation of bioanalytical methods for dried blood spots. Bioanalysis. 2011; 3(14):1567-75. DOI: 10.4155/bio.11.132. View

13.

Kneepkens E, Pouw M, Wolbink G, Schaap T, Nurmohamed M, de Vries A . Dried blood spots from finger prick facilitate therapeutic drug monitoring of adalimumab and anti-adalimumab in patients with inflammatory diseases. Br J Clin Pharmacol. 2017; 83(11):2474-2484. PMC: 5651343. DOI: 10.1111/bcp.13371. View

14.

Prevoo M, van t Hof M, Kuper H, van Leeuwen M, van de Putte L, van Riel P . Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995; 38(1):44-8. DOI: 10.1002/art.1780380107. View

15.

Southan C, Sharman J, Benson H, Faccenda E, Pawson A, Alexander S . The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucleic Acids Res. 2015; 44(D1):D1054-68. PMC: 4702778. DOI: 10.1093/nar/gkv1037. View

16.

Plasencia C, Kneepkens E, Wolbink G, Krieckaert C, Turk S, Navarro-Compan V . Comparing Tapering Strategy to Standard Dosing Regimen of Tumor Necrosis Factor Inhibitors in Patients with Spondyloarthritis in Low Disease Activity. J Rheumatol. 2015; 42(9):1638-46. DOI: 10.3899/jrheum.141128. View

17.

van Schouwenburg P, Kruithof S, Votsmeier C, van Schie K, Hart M, de Jong R . Functional analysis of the anti-adalimumab response using patient-derived monoclonal antibodies. J Biol Chem. 2014; 289(50):34482-8. PMC: 4263856. DOI: 10.1074/jbc.M114.615500. View

18.

Wilhelm A, den Burger J, Swart E . Therapeutic drug monitoring by dried blood spot: progress to date and future directions. Clin Pharmacokinet. 2014; 53(11):961-73. PMC: 4213377. DOI: 10.1007/s40262-014-0177-7. View

19.

Bloem K, van Leeuwen A, Verbeek G, Nurmohamed M, Wolbink G, van der Kleij D . Systematic comparison of drug-tolerant assays for anti-drug antibodies in a cohort of adalimumab-treated rheumatoid arthritis patients. J Immunol Methods. 2015; 418:29-38. DOI: 10.1016/j.jim.2015.01.007. View

20.

Krieckaert C, Nair S, Nurmohamed M, van Dongen C, Lems W, Lafeber F . Personalised treatment using serum drug levels of adalimumab in patients with rheumatoid arthritis: an evaluation of costs and effects. Ann Rheum Dis. 2013; 74(2):361-8. DOI: 10.1136/annrheumdis-2013-204101. View