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

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.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Adalimumab / blood*
  • Adalimumab / immunology
  • Adalimumab / therapeutic use
  • Adult
  • Aged
  • Antibodies / blood*
  • Antibodies / immunology
  • Antirheumatic Agents / blood*
  • Antirheumatic Agents / immunology
  • Antirheumatic Agents / therapeutic use
  • Blood Specimen Collection / methods
  • Cross-Sectional Studies
  • Dried Blood Spot Testing*
  • Drug Monitoring / methods*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fingers
  • Humans
  • Male
  • Middle Aged
  • Phlebotomy
  • Rheumatic Diseases / blood
  • Rheumatic Diseases / drug therapy*
  • Tandem Mass Spectrometry

Substances

  • Antibodies
  • Antirheumatic Agents
  • Adalimumab