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.
- Rheumatoid Arthritis
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Contributors Acquisition and interpretation of data and critical revision of the manuscript for important intellectual content was done by KvS, POdH, SK, CP, TJ, DPS, JFB, GRAMdH, GJW and TR. Experiments were performed and data were analysed and discussed by KvS, POdH and SK. Manuscript was written by KvS and TR, experiments were designed by TR. The data were analysed and discussed, and the study was designed by GJW and TR.
Funding JFB reports speaker fees from: Merck Sharp & Dohme, Abbvie and Takeda pharmaceuticals, outside the submitted work. GRAMd'H reports grants from AbbVie, Janssen, Given Imaging, MSD, Dr Falk Pharma, PhotoPill, consulting and/or lecture fees from Abbvie, ActoGeniX, AIM, Boehringer Ingelheim GmbH, Centocor, ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, enGene, Dr Falk Pharma, Ferring, Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline, Janssen Biologics, MSD, Neovacs, Novo Nordisk, Otsuka, PDL BioPharma, Pfizer, Receptos, Salix, SetPoint, Shire Pharmaceuticals, Schering-Plough, Takeda, Tillotts Pharma, UCB Pharma, Versant, Vifor Pharma and speaking honoraria from AbbVie, Tillotts, Tramedico, Ferring, MSD, UCB Pharma, Norgine, Shire, outside the submitted work. GW reports grants from Pfizer during the conduct of the study; grants from Pfizer, payment for lectures from Pfizer, Abbvie and UCB outside the submitted work. TR reports grants from Pfizer during the conduct of the study; grants from Genmab, consultancy fees from Genmab and payment for lectures from Pfizer, Abbvie and Regeneron outside the submitted work. PO-dH, TJ and DP-S have nothing to disclose.
Disclaimer Pfizer had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.
Ethics approval The study was approved by the local medical ethical committees in Spain and the Netherlands.
Provenance and peer review Not commissioned; externally peer reviewed.