Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis

Rheumatology (Oxford). 2011 Aug;50(8):1445-52. doi: 10.1093/rheumatology/ker124. Epub 2011 Mar 22.

Abstract

Objective: To analyse the clinical relevance of the production of anti-infliximab antibodies (anti-infliximab Abs) in patients with RA undergoing infliximab treatment over a prolonged period of time.

Methods: Clinical characteristics, serum trough infliximab and antibody levels were evaluated in 85 RA patients treated with infliximab for a median of 4.42 (interval 0.4-10.2) years. DAS in 28 joints (DAS-28), EULAR response criteria and survival of treatment were assessed at 3 time points (6 months, 12 months and >4 years).

Results: Antibodies against infliximab were detected in 28 (32.9%) patients and were present in all EULAR non-responder patients. Antibody levels were higher in EULAR non-responders throughout the study period (P = 0.05 at 6 months, P = 0.02 at 1 year, P = 0.003 at >4 years) compared with EULAR (good and moderate) responders. Nine (10.5%) patients, all of them with high-serum anti-infliximab Ab levels, developed infusion-related reactions. Patients with anti-infliximab Abs more often required increased infliximab doses (51.7%) (P = 0.032) and median survival time on treatment was shorter (4.15 vs 8.89 years) (P = 0.0006). MTX co-therapy was not associated with lower proportion of anti-infliximab Ab-positive patients, but those receiving both infliximab and MTX had lower levels of anti-infliximab Abs (P = 0.073) and longer survival (P = 0.015) on treatment.

Conclusion: The formation of anti-infliximab Abs during treatment with infliximab is associated with a loss of clinical response, the appearance of infusion reactions and discontinuation of treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / blood
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / immunology
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / immunology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology*
  • Drug Therapy, Combination
  • Drug Tolerance / immunology
  • Female
  • Humans
  • Infliximab
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Infliximab
  • Methotrexate