Infusion reactions during infliximab treatment are not associated with IgE anti-infliximab antibodies

Ann Rheum Dis. 2017 Jul;76(7):1285-1288. doi: 10.1136/annrheumdis-2016-211035. Epub 2017 Apr 28.

Abstract

Objectives: Controversy exists on the role of IgE antidrug antibodies (IgE-ADA) in infusion reactions (IR) on infliximab treatment, partly due to the lack of a positive control used for assay validation. We sought to (1) develop a robust assay to measure IgE-ADA, including a positive control, (2) determine the association between IgE-ADA and IR and (3) determine the incidence of IgE-ADA in infliximab treated patients.

Methods: A recombinant human IgE anti-infliximab monoclonal antibody was developed as standard and positive control. With this antibody, we set up a novel robust assay to measure IgE-ADA. IgE-ADA was determined in three retrospective cohorts (n=159) containing IR+ (n=37) and IR- (n=39), and longitudinal sera of 83 spondyloarthritis.

Results: IgE-ADA was found in 0/39 IR-, whereas 4/37 (11%) IR+ showed low levels (0.1-0.3 IU/mL, below the 0.35 IU/mL threshold associated with elevated risk of allergic symptoms). All patients who were IgE-ADA positive also had (very) high IgG-ADA levels. The incidence of IgE-ADA in patients with infliximab-treated spondyloarthritis was estimated at less than approximately 1%.

Conclusions: IgE-ADA is rarely detected in infliximab-treated patients. Moreover, the absence of IgE-ADA in the majority of IR+ patients suggests that IgE-ADA is not associated with infusion reactions.

Keywords: Anti-TNF; Rheumatoid Arthritis; Spondyloarthritis.

MeSH terms

  • Antibodies / immunology*
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy
  • Cohort Studies
  • Dyspnea / chemically induced*
  • Dyspnea / immunology
  • Flushing / chemically induced*
  • Flushing / immunology
  • Humans
  • Immunoglobulin E / immunology*
  • Infliximab / adverse effects*
  • Infliximab / immunology
  • Infusions, Intravenous / adverse effects*
  • Pruritus / chemically induced*
  • Pruritus / immunology
  • Spondylarthritis / drug therapy
  • Spondylarthropathies / drug therapy
  • Urticaria / chemically induced

Substances

  • Antibodies
  • Antirheumatic Agents
  • Immunoglobulin E
  • Infliximab