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Monitoring immunogenicity of protein-based TNF antagonists
  1. Klaus Bendtzen1,
  2. Casper Steenholdt2,
  3. Jørn Brynskov2,
  4. Ole Ø Thomsen2,
  5. Mark A Ainsworth2
  1. 1 Institute for Inflammation Research, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark
  2. 2 Department of Gastroenterology, Herlev Hospital, Copenhagen, Denmark
  1. Correspondence to Professor Klaus Bendtzen, Institute for Inflammation Research (IIR7521), University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, Copenhagen N DK-2100, Denmark; klausben{at}me.com

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A recent review by Hendy et al 1 discusses the use of anti-tumour necrosis factor (TNF) drug and anti-drug antibody (ADAb) measurements to achieve a personalised approach to treating patients with inflammatory bowel disease with loss of response (LOR) to protein-based TNF-antagonist therapy. While highly appreciated and filling an important gap in the current management of patients with LOR, the review leaves out important pharmacoimmunological information related to drug immunogenicity, particularly the clinical relevance of technologies used to measure ADAb.2

It should be noted that blood levels of infused or injected anti-TNF drugs vary considerably in the periods between repeated drug administrations (figure 1). Assessing circulating drug levels is therefore highly dependent upon the time from drug administration to blood sampling. If ADAb develops, these variations are even more complex, and assessments of drug and ADAb become dependent on time of blood sampling and on the kinetics of binding between drug and ADAb. The latter governs formation of immune complexes containing drug and ADAb, the size and stability of these complexes, their ability to bind and activate other serum components such as complement and, subsequently, elimination of the immune complexes from the circulation. In this scenario, the test characteristics of a given assay will markedly affect the reported levels of both drug and ADAb. While a test designed …

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Footnotes

  • Contributors Conception and drafting of manuscript: KB. Contribution and revision of manuscript, approval of final manuscript: all authors.

  • Competing interests KB has served as a speaker for Pfizer and Biomonitor and owns stocks in Novo-Nordisk and Eurodiagnostica. CS has served as speaker for MSD and Abbvie and as a consultant for MSD, Takeda Pharmaceutical Company Limited and Pfizer. JB has served as advisory board member for Abbvie. OØT has served as a speaker and consultant for UCB and Zealand Pharma and primary investigator for Amgen, Celltrion, Genetech, Novo-Nordisk, Pfizer and Roche.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • i In contrast to Hendy et al, we have no knowledge of laboratories that provide ELISAs that ‘give reliable ADAb levels in the presence of drug’.

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