New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors

A systematic analysis

Pier Luigi Meroni, Gabriele Valentini, Fabio Ayala, Antonino Cattaneo, Guido Valesini

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Aim: To assess the putative link between antibody formation to adalimumab, infliximab and etanercept, circulating drug levels and clinical outcomes. Methods: A literature search was conducted using Pubmed from inception to 5th March 2013 of original research articles relating to adalimumab, etanercept and infliximab that investigated the immunogenicity of each drug. Data were extracted to document the disease, anti-TNF-α agent, regimen, study design, use of concomitant immunosuppressive therapy, the relationship between drug administration and antibody assessment, the type of immunoassay and cut-off, plasma drug concentration, frequency of antibody and clinical assessments, antibody positivity rate and relationship between antibody positivity and clinical outcome. Studies were stratified by drug, disease area and whether or not concomitant immunosuppressive therapy had been given. All data were tabulated by publication and analyzed descriptively. Results: A total of 57 original research articles were included in the analysis (infliximab n = 34; adalimumab n = 18; etanercept n = 5). There was considerable heterogeneity in study design, methodology for anti-drug antibody detection and drug bioavailability evaluation. Consequently, it was difficult to compare the immunogenic potential of infliximab, adalimumab and etanercept, particularly because different assays with variable sensitivity and specificity were used. The timing of occurrence and the persistence of anti-drug antibodies appeared to be influenced by administration schedules and concomitant immunosuppressive therapy. Monitoring of circulating drug levels and anti-drug antibodies appears to be an emerging and cost-effective strategy for the management of the individual patient. Conclusions: Monitoring drug and anti-drug antibody levels appears to be a putative strategy for optimal and cost-effective intervention. However studies of consistent and homogeneous design, methodology and duration are warranted to assess the true incidence and consequences of immunogenicity.

Original languageEnglish
Pages (from-to)812-829
Number of pages18
JournalAutoimmunity Reviews
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

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Pharmacokinetics
Tumor Necrosis Factor-alpha
Pharmaceutical Preparations
Anti-Idiotypic Antibodies
Immunosuppressive Agents
Antibodies
Drug Monitoring
Costs and Cost Analysis
Drug Evaluation
Immunoassay
Research
PubMed
Biological Availability
Antibody Formation
Publications
Appointments and Schedules
Therapeutics
Sensitivity and Specificity
Infliximab
Adalimumab

Keywords

  • Adalimumab
  • Anti-drug detection
  • Drug bioavailability
  • Etanercept
  • Infliximab
  • Systematic review
  • TNFα inhibitors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors : A systematic analysis. / Meroni, Pier Luigi; Valentini, Gabriele; Ayala, Fabio; Cattaneo, Antonino; Valesini, Guido.

In: Autoimmunity Reviews, Vol. 14, No. 9, 01.09.2015, p. 812-829.

Research output: Contribution to journalArticle

Meroni, Pier Luigi ; Valentini, Gabriele ; Ayala, Fabio ; Cattaneo, Antonino ; Valesini, Guido. / New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors : A systematic analysis. In: Autoimmunity Reviews. 2015 ; Vol. 14, No. 9. pp. 812-829.
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KW - Systematic review

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