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Immunogenicity to infliximab is associated with HLA-DRB1
  1. Thomas Billiet1,
  2. Niels Vande Casteele2,
  3. Thomas Van Stappen2,
  4. Fred Princen3,
  5. Sharat Singh3,
  6. Ann Gils2,
  7. Marc Ferrante4,
  8. Gert Van Assche4,
  9. Isabelle Cleynen4,
  10. Severine Vermeire4
  1. 1Department of Clinical and Experimental Medicine, Translational Research Center for GastroIntestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
  2. 2Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
  3. 3Department of Research and Development, Prometheus Laboratories, San Diego, California, USA
  4. 4Department of Gastroenterology, UZ Leuven, Leuven, Belgium
  1. Correspondence to Dr Severine Vermeire, Gastroenterology Department, University Hospitals Leuven, Herestraat 49, Leuven B-3000, Belgium; severine.vermeire{at}

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Dear Editor,

We read with great interest the manuscript by Ungar and colleagues describing the temporal evolution of antibodies to infliximab (ATI) in patients with IBD treated with infliximab (IFX).1 By prospectively following 125 patients with IBD, they showed that ATI formation is a dynamic process. Clinically relevant ATI were typically formed within the first 12 months but transient ATI, which are of little clinical significance, can be formed at any time during treatment. They furthermore demonstrated that the evolution of ATI correlates with clinical loss of response and that concomitant immunomodulator use prolonged ATI-free survival, which is in line with previous reports. Nevertheless, patient-related factors possibly influencing ATI formation weren't considered and haven't been studied extensively. We hypothesised that ATI formation may be triggered by HLA-DRB1 alleles, as was shown for immunogenicity to interferon-β therapy in multiple sclerosis.2 We retrospectively analysed 192 patients with IBD: 76 patients developed ATI during IFX maintenance treatment (=ATI+) (44 Crohn's disease (CD), 32 UC) and these were matched with 116 patients (64 CD, 52 UC) who never developed ATI (=ATI−). All patients were antitumour necrosis factor naïve before IFX …

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  • Contributors TB: data acquisition and interpretation, statistical analysis and drafting of the manuscript; NvdC: data acquisition and interpretation, critical revision of the manuscript; TvS: data acquisition and critical revision of the manuscript; AG, MF, GVA and IC: critical revision of the manuscript; SV: study concept—design and supervision, critical revision of the manuscript; FP and SS: technical support.

  • Funding FWO Vlaanderen (G.0617.12).

  • Competing interests NvdC received a lecture fee from Abbvie and consultancy fees from MSD, Janssen Biotech, UCB and Pfizer. FP and SS are employees of Prometheus Laboratories. AG received financial support for research from FWO and lecture fees from MSD, Abbvie, Janssen Biologicals, Pfizer. MF received financial support for research from Janssen Biologics, lecture fees from MSD, Ferring Pharmaceuticals, Chiesi, MSD, Tillotts, Janssen Biologics, Abbott and Abbvie and consultancy fees from Abbott, Abbvie, MSD and Janssen Biologics. GVA received financial support for research from Abbott and Ferring Pharmaceuticals, lecture fees from Janssen, MSD and Abbott and consultancy fees from PDL BioPharma, UCB Pharma, Sanofi-Aventis, Abbott, Abbvie, Ferring, Novartis, Biogen Idec, Janssen Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis and Bristol Mayer Squibb. SV received financial support for research from MSD, Abbvie and UCB Pharma, lecture fees from Abbott, Abbvie, MSD, Ferring Pharmaceuticals and UCB Pharma and consultancy fees from Pfizer, Ferring Pharmaceuticals, Shire Pharmaceuticals Group, MSD and AstraZeneca Pharmaceuticals. TB, TVS and IC disclose no conflicts of interest.

  • Ethics approval Ethische commissie UZ Leuven.

  • Provenance and peer review Not commissioned; internally peer reviewed.