title: 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.
abstract: 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 (Delta DAS28) for the 235 patients was 1.6+/-1.5 (mean+/-SD). Anti-adalimumab antibodies were detected in 46 patients (20%). Delta DAS28 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). Delta DAS28 was greater for anti-TNF naive patients (1.7+/-1.5) than for switchers without anti-infliximab antibodies (Delta DAS28=0.9+/-1.4) (p=0.009). Delta DAS28 for switchers with anti-infliximab was 1.2+/-1.3 and did not differ significantly from anti-TNF naive patients (p=0.262).
  
  
  CONCLUSIONS
  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.
authors: Department of Rheumatology, Jan van Breemen Institute, Dr Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands.
authors: G M
authors: GM
authors: Bartelds
authors: C A
authors: CA
authors: Wijbrandts
authors: M T
authors: MT
authors: Nurmohamed
authors: S
authors: S
authors: Stapel
authors: W F
authors: WF
authors: Lems
authors: L
authors: L
authors: Aarden
authors: B A C
authors: BA
authors: Dijkmans
authors: P P
authors: PP
authors: Tak
authors: G J
authors: GJ
authors: Wolbink
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000276:immunology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab