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Pre‐existing IgG antibodies cross‐reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease
Author(s) -
Steenholdt C.,
Palarasah Y.,
Bendtzen K.,
Teisner A.,
Brynskov J.,
Teisner B.,
Nielsen C. H.
Publication year - 2013
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12330
Subject(s) - infliximab , medicine , ulcerative colitis , inflammatory bowel disease , gastroenterology , antibody , cohort , retrospective cohort study , maintenance therapy , pharmacokinetics , immunology , disease , chemotherapy
Summary 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.