The effect of antidrug antibodies on the sustainable efficacy of biologic therapies in rheumatoid arthritis: practical consequences

Expert Rev Clin Immunol. 2014 Aug;10(8):1049-57. doi: 10.1586/1744666X.2014.926219. Epub 2014 Jun 25.

Abstract

Biologic therapies, predominantly TNF-α inhibitors, have revolutionized the treatment of rheumatoid arthritis (RA). However, their clinical utility can be limited by the development of antidrug antibodies (ADAs). Immunogenicity is a complex phenomenon related to various drug, disease, and patient characteristics, and may be more common with the monoclonal antibodies than with etanercept, a soluble TNF receptor-Fc immunoglobulin fusion protein. Neutralizing antibodies - those that hinder bioactivity by preventing drug molecules from binding to TNF - are correlated with reduced serum drug concentrations, loss of therapeutic response, adverse events, and treatment discontinuation. Cost-effective use of these agents will depend on further research into drug and ADA assays, and how they should guide dose reduction or switching strategies.

Keywords: TNF antagonists; abatacept; adalimumab; antidrug antibodies; biologic therapies; etanercept; immunogenicity; infliximab; rheumatoid arthritis; rituximab.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Blocking / metabolism*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / economics
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • Drug Substitution
  • Etanercept
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunotherapy*
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use
  • Withholding Treatment

Substances

  • Antibodies, Blocking
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • Etanercept