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The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept
  1. Anna Jamnitski1,
  2. Geertje M Bartelds1,
  3. Michael T Nurmohamed1,2,
  4. Pauline A van Schouwenburg3,
  5. Dirkjan van Schaardenburg1,2,
  6. Steven O Stapel3,
  7. Ben A C Dijkmans1,2,
  8. Lucien Aarden3,
  9. Gerrit Jan Wolbink1,3
  1. 1Jan van Breemen Institute, Amsterdam, The Netherlands
  2. 2VU University Medical Centre, Amsterdam, The Netherlands
  3. 3Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands
  1. Correspondence to Dr G J Wolbink, Department of Rheumatology, Jan van Breemen Institute, Dr Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands; g.wolbink{at}


Objective The aim of this study was to test the hypothesis that the reason for non-response (caused by immunogenicity or not) to a first tumour necrosis factor (TNF) inhibitor defines whether a second TNF inhibitor will be effective.

Methods This cohort study consisted of 292 consecutive patients with rheumatoid arthritis (RA), all treated with etanercept. A total of 89 patients (30%) were treated previously with infliximab or adalimumab (‘switchers’), and the remaining 203 (70%) were anti-TNF naive. All switchers were divided into two groups: with and without antibodies against the previous biological. Differences in clinical response to etanercept between switchers with and without antibodies and patients who were anti-TNF naive were assessed after 28 weeks of treatment using changes in Disease Activity Score in 28 joints (DAS28).

Results After 28 weeks of treatment, response to etanercept did not differ between patients who were anti-TNF naive and switchers with anti-drug antibodies (ΔDAS28=2.1±1.3 vs ΔDAS28=2.0±1.3; p=0.743). In contrast, switchers without anti-drug antibodies had a diminished response to etanercept treatment compared to patients who were TNF naive (ΔDAS28=1.2±1.3 vs ΔDAS28=2.1±1.3; p=0.001) and switchers with antibodies (ΔDAS28=1.2±1.3 vs ΔDAS28=2.0±1.3; p=0.017).

Conclusion Patients with RA with an immunogenic response against a first TNF-blocking agent had a better clinical response to a subsequent TNF blocker compared to patients with RA without anti-drug antibodies. Hence, determining immunogenicity can be helpful in deciding in which patient switching could be beneficial and can be part of a personalised treatment regimen.

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  • Funding The clinical part of this study was partially financed by Wyeth Pharmaceuticals. In addition, this investigation was also facilitated by the Clinical Research Bureau of the Jan van Breemen Institute.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the METC slotervaart ziekenhuis.

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