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

Ann Rheum Dis. 2010 May;69(5):817-21. doi: 10.1136/ard.2009.112847. Epub 2009 Jul 5.

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).

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / immunology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Cohort Studies
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Infliximab
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab