Pre-existing IgG antibodies cross-reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease

Casper Steenholdt, Yaseelan Palarasah, Klaus Bendtzen, Ane Søgaard Teisner, J. Brynskov, B Teisner, C H Nielsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background Infliximab (IFX) is a chimeric murine/human anti-TNF antibody (Ab) used for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Loss of response is common and associated with development of anti-IFX Abs during ongoing therapy. However, human anti-murine immunoglobulin Abs are common and may cross-react with the murine part of IFX. Aim To investigate if Abs binding to IFX's Fab region (IFX-Fab) are present in IBD patients before exposure to IFX, and whether they predict efficacy and safety of IFX therapy. Methods Observational, retrospective cohort study of patients with CD (n = 29) and UC (n = 22). Results Pre-treatment levels of IFX-Fab reactive IgG Abs were significantly lower in CD patients in remission after 1 year of maintenance IFX (median 91 mU/L, n = 8) than in the rest of the patients (639 mU/L, n = 21; P < 0.01), and lower than in patients with secondary loss of response in particular (692 mU/L, n = 7; P < 0.01). A cut-off concentration of <439 mU IFX-Fab reactive IgG Ab per litre comprised all patients who later obtained long-term sustained remission on IFX (sensitivity 100%, specificity 67%). Similar trends were observed in UC. The pre-treatment levels of IFX-Fab reactive IgG Abs were markedly higher in patients developing infusion reactions to IFX (1037 mU/L, n = 7) than in the remaining patients (349 mU/L, n = 44; P = 0.036). Conclusions IFX-Fab reactive IgG antibodies present in serum from IBD patients before infliximab therapy associate with lack of long-term efficacy and safety. Assessments of such antibodies may help clinicians to choose between treatment with infliximab and more humanised agents.

Original languageEnglish
JournalAlimentary Pharmacology and Therapeutics
Volume37
Issue number12
Pages (from-to)1172–1183
ISSN0269-2813
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Adult
  • Antibodies, Monoclonal/immunology
  • Cohort Studies
  • Cross Reactions/immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gastrointestinal Agents/immunology
  • Humans
  • Immunoglobulin Fab Fragments/immunology
  • Immunoglobulin G/blood
  • Inflammatory Bowel Diseases/drug therapy
  • Infliximab
  • Male
  • Predictive Value of Tests
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Young Adult

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