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

Aliment Pharmacol Ther. 2013 Jun;37(12):1172-83. doi: 10.1111/apt.12330. Epub 2013 May 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Infliximab