title: Pre-existing IgG antibodies cross-reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease.
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.
  
  
  OBJECTIVE
  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.
authors: Department of Gastroenterology, Herlev Hospital, Herlev, Denmark.
authors: C
authors: C
authors: Steenholdt
authors: Y
authors: Y
authors: Palarasah
authors: K
authors: K
authors: Bendtzen
authors: A
authors: A
authors: Teisner
authors: J
authors: J
authors: Brynskov
authors: B
authors: B
authors: Teisner
authors: C H
authors: CH
authors: Nielsen
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D015331:Cohort Studies; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005765:Gastrointestinal Agents / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology*; D000069285:Infliximab; D008297:Male; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D000069285:Infliximab