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Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study
  1. G M Bartelds1,
  2. C A Wijbrandts2,
  3. M T Nurmohamed1,3,
  4. S Stapel4,
  5. W F Lems3,
  6. L Aarden4,
  7. B A C Dijkmans1,3,
  8. P P Tak2,
  9. G J Wolbink1,4
  1. 1Jan van Breemen Institute, Amsterdam, The Netherlands
  2. 2Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands
  3. 3VU University Medical Centre, Amsterdam, The Netherlands
  4. 4Landsteiner Laboratory Sanquin Research, 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 To investigate how antibodies against anti-tumour necrosis factor (anti-TNF) agents influence response after switching from infliximab to adalimumab in rheumatoid arthritis (RA).

Methods This cohort study consisted of 235 patients with RA, all treated with adalimumab. At baseline 52 patients (22%) had been previously treated with infliximab (‘switchers’), and 183 (78%) were anti-TNF naive. Disease activity (using the 28-joint count Disease Activity Score (DAS28)) and presence of antibodies against infliximab and adalimumab were assessed. Clinical response to adalimumab was compared between switchers and anti-TNF naive patients and their anti-infliximab and anti-adalimumab antibody status.

Results After 28 weeks of adalimumab treatment the decrease in DAS28 (ΔDAS28) for the 235 patients was 1.6±1.5 (mean±SD). Anti-adalimumab antibodies were detected in 46 patients (20%). ΔDAS28 was 1.8±1.4 in patients without anti-adalimumab and 0.6±1.3 in patients with anti-adalimumab (p<0.0001). Thirty-three of the 52 switchers (63%) had anti-infliximab antibodies. Patients with anti-infliximab more often developed anti-adalimumab than anti-TNF naive patients (11 (33%) vs 32 (18%); p=0.039). ΔDAS28 was greater for anti-TNF naive patients (1.7±1.5) than for switchers without anti-infliximab antibodies (ΔDAS28=0.9±1.4) (p=0.009). ΔDAS28 for switchers with anti-infliximab was 1.2±1.3 and did not differ significantly from anti-TNF naive patients (p=0.262).

Conclusion Switchers with anti-infliximab antibodies more often develop antibodies against adalimumab than anti-TNF naive patients. Response to adalimumab was limited in switchers without anti-infliximab antibodies, which raises the question whether a second anti-TNF treatment should be offered to patients with RA for whom an initial treatment with an anti-TNF blocker fails, in the absence of anti-biological antibodies.

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  • GMB and CAW contributed equally.

  • Funding The clinical part of this study was partially financed by Abbott and Wyeth. CAW was supported by grant number 945-02-029 from the Netherlands Organisation for Health Research and Development (ZonMw) to PPT. The study sponsors had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

  • Competing interests BACD, PPT and WFL are members of the advisory board of Abbott and BACD and PPT have received honoraria for lectures. PPT has served as a consultant to Abbott, Amgen, Centocor, Schering-Plough, UCB and Wyeth.

  • Ethics approval The study was approved by the medical ethics committee of the Slotervaart Hospital, BovenIJ Hospital, the Jan van Breemen Institute and the Academic Medical Centre/University of Amsterdam.

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