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12. Pre-existing IgG antibodies to the Fab region of infliximab predict efficacy and safety in IBD patients naive to anti-TNF agents

C. Steenholdt1, Y. Palarasah2, K. Bendtzen2, A. Teisner3, B. Teisner2, J. Brynskov1, C. Nielsen2, 1Herlev Hospital, Dept of Gastroenterology, Herlev, 2Rigshospitalet, University Hospital of Copenhagen, Institute for Inflammation Research, Dept. of Infectious Diseases and Rheumatology, Copenhagen, 3Odense Hospital, Dept of Medical Gastroenterology S, Odense, Denmark

Background

Infliximab (IFX) is a chimeric (mouse/human) anti-TNF antibody (Ab) that has a well-established role in the treatment of inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). Primary non-response and loss of response is common and associated with development of anti-IFX Abs during ongoing therapy. However, recent data from our laboratory suggest that low levels of IgG Abs to the murine part of IFX's Fab region exist in healthy blood donors. We assessed whether anti-IFX Fab IgG Abs were also present in IBD patients naive to biologics, and whether their presence affected efficacy and safety of subsequent IFX treatment.

Methods

Observational, retrospective, single-center cohort study of patients with CD (n = 29) and UC (n = 22). Patient serum samples obtained prior to IFX therapy, were analyzed for anti-IFX Abs of IgG isotype using an ELISA based on matrix-coupled IFX Fab and detection with monoclonal anti-human IgG.

Results

Pre-treatment anti-IFX Fab IgG Ab levels were lower in CD patients in remission after one year of maintenance IFX (median 91 mU/l, n = 8) than in all other CD patients (639 mU/l, n = 21; p < 0.01); as well as in subgroups with primary non-response (308 mU/l, n = 8; p < 0.05) or secondary loss of response (692 mU/l, n = 7; p < 0.01). An anti-IFX Fab IgG Ab cut-off concentrations of <430 mU/l prior to initiation of IFX therapy identified all patients who later obtained long-term sustained remission on IFX (sensitivity 100%, specificity 67%). Similar trends were observed in UC. Total levels of IgG subtypes, IgM, IgA, and IgE were similar among patients with or without remission. Pre-treatment anti-IFX Fab IgG Ab levels were markedly higher in patients developing infusion reactions to IFX (1,037 mU/l; n = 7) than in remaining patients (349 mU/l, n = 44; p = 0.036).

Conclusion

Anti-IFX Fab IgG Abs present in serum from IBD patients prior to initiation of IFX therapy associate with long-term clinical efficacy and safety. Assessments of such Abs may help clinicians to choose between treatment with IFX or more ‘humanized’ agents.