Article Text

Concise report
The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region
  1. K A van Schie1,2,
  2. M H Hart1,2,
  3. E R de Groot1,2,
  4. S Kruithof1,2,
  5. L A Aarden1,2,
  6. G J Wolbink1,2,3,
  7. T Rispens1,2
  1. 1Sanquin Research, Department of Immunopathology, Amsterdam, The Netherlands
  2. 2Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  3. 3Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands
  1. Correspondence to Dr Theo Rispens, Sanquin Blood Supply, Plesmanlaan 125, Amsterdam 1066 CX, The Netherlands; T.rispens{at}


Background In a subset of patients, anti tumour necrosis factor (TNF) therapeutic antibodies are immunogenic, resulting in the formation of antidrug antibodies (ADAs). Neutralising ADAs compete with TNF for its binding site and reduces the effective serum concentration, causing clinical non-response. It is however unknown to which extent ADAs are neutralising.

Objectives To study which proportion of antibodies to human(ised) anti-TNF (adalimumab, golimumab, certolizumab) as well as chimeric anti-TNF (infliximab) is neutralising.

Methods Neutralising capacity of ADAs was assessed using a TNF competition assay in ADA-positive sera of patients treated with adalimumab (n=21), golimumab (n=4), certolizumab (n=9) or infliximab (n=34) sent in to our diagnostic department.

Results In 34 sera with ADAs to adalimumab, golimumab or certolizumab, >97% of the antibodies were neutralising. In 34 sera with ADAs to infliximab >90% of the antibodies were neutralising. Further characterisation of the broader antibody response to infliximab revealed that non-neutralising antibodies to infliximab do not target murine domains, but may bind infliximab-unique domains not involved in TNF binding (located outside the paratope).

Conclusions Our study shows that ADAs to human(ised) as well as chimeric anti-TNF therapeutic antibodies are largely neutralising. This highly restricted ADA response suggests an immunodominant role for the paratope of anti-TNF therapeutics.

  • Anti-TNF
  • Rheumatoid Arthritis
  • TNF-alpha
View Full Text

Statistics from

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Files in this Data Supplement:

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.