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Predicting efficacy and safety of infliximab therapy in IBD

Pre-existing IgG antibodies cross-reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease, reports June's publication of the Alimentary Pharmacology & Therapeutics.

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Infliximab is a chimeric murine/human anti-TNF antibody (Ab) used for the treatment of Crohn's disease and ulcerative colitis.

Loss of response is common and associated with development of anti-Infliximab antibodies during ongoing therapy.

However, human anti-murine immunoglobulin antibodies are common and may cross-react with the murine part of Infliximab.

Dr Steenholdt and colleagues investigated whether antibodies binding to Infliximab's Fab region are present in IBD patients before exposure to Infliximab, and whether they predict efficacy and safety of Infliximab therapy.

The team performed an observational, retrospective cohort study of patients with Crohn's disease and ulcerative colitis.

The doctors noted that pre-treatment levels of Infliximab-Fab reactive IgG antibodies were significantly lower in Crohn's disease patients in remission after 1 year of maintenance Infliximab than in the rest of the patients, and lower than in patients with secondary loss of response in particular.

A cut-off of 439 mU infliximab-Fab reactive IgG Ab per litre comprised  patients with long-term remission
Alimentary Pharmacology & Therapeutics

A cut-off concentration of 439 mU infliximab-Fab reactive IgG antibody per litre comprised all patients who later obtained long-term sustained remission on Infliximab.

The researchers observed similar trends in ulcerative colitis.

The pre-treatment levels of Infliximab-Fab reactive IgG antibodies were markedly higher in patients developing infusion reactions to Infliximab than in the remaining patients.

Dr Steenholdt's team concluded, "Infliximab-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 humanized agents."

Aliment Pharmacol Ther 2013: 37(12): 117-1183
29 May 2013

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