You are here

  • Home
  • Archive
  • Volume 60, Issue 1
  • The immunogenic part of infliximab is the F(ab′)2, but measuring antibodies to the intact infliximab molecule is more clinically useful

Article Text

Article menu
Download PDFPDF
Inflammatory bowel disease
Paper
The immunogenic part of infliximab is the F(ab′)2, but measuring antibodies to the intact infliximab molecule is more clinically useful
  1. Shomron Ben-Horin,
  2. Miri Yavzori,
  3. Lior Katz,
  4. Uri Kopylov,
  5. Orit Picard,
  6. Ella Fudim,
  7. Daniel Coscas,
  8. Simon Bar-Meir,
  9. Itamar Goldstein,
  10. Yehuda Chowers
  1. Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  1. Correspondence to Shomron Ben-Horin, Department of Gastroenterology, Sheba Medical Center, Tel Hashomer 52621, Tel Aviv University, Tel Aviv, Israel; sben-horin{at}013.net.il

Abstract

Objectives To localise the immunogenic part of infliximab and evaluate the clinical usefulness of measuring antibodies against infliximab fragments.

Design Observational study.

Settings A specialised inflammatory bowel disease (IBD) centre in a tertiary hospital.

Interventions Serum was collected from patients with IBD and controls. Antibodies against whole infliximab (ATI) and against the digested Fc, F(ab′)2 and F(ab′) fragments were measured by a specifically developed ELISA and by western blotting. A separate ELISA was used to determine infliximab levels in serum.

Results 109 serum samples from 62 infliximab-treated patients were tested along with 64 control samples. Anti-F(ab′)2 antibodies were found in 28/42 (67%) samples with positive ATI, all from infliximab-exposed patients. Anti-F(ab′)2 antibodies were also present in 26 of the remaining 67 (39%) samples from exposed patients despite absent ATI. No specific anti-Fc antibodies were detected. Low trough infliximab level and high ATI level was found in 10/12 patients (83%) with complete loss of response to infliximab, but in only 5/14 patients (36%, p=0.02) who regained response to intensified infliximab regimen and in 2/24 patients (8%, p<0.001) in maintained remission while on 5 mg/kg/8 week infliximab treatment. Although Anti-F(ab′)2 antibodies showed similar test characteristics to ATI in patients losing response to infliximab, they were also detected in 61% of patients in maintained remission, thereby limiting their clinical usefulness. No cross reactivity to adalimumab was noted.

Conclusions F(ab′)2 is the immunogenic fragment of infliximab. However, ATI level in serum—combined with measurement of trough infliximab level—is better correlated with the clinical response to infliximab or with its loss.

  • Inflammatory bowel disease
  • antibodies
  • therapy
  • immunology
  • inflammatory bowel disease

https://doi.org/10.1136/gut.2009.201533

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Funding The study was supported in part by a ‘Talpiot’ unrestricted research grant from the Sheba Medical Center (to SBH).

    • Competing interests SBH and YC have received consultancy fees from Abbott Laboratories and Schering-Plough.

    • Ethics approval This study was conducted with the approval of the Sheba Medical Center.

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