2008 - Marseille - France

PAGE 2008: Applications- Biologicals/vaccines
David Ternant

Development of anti-infliximab antibodies increases infliximab clearance in inflammatory bowel diseases

D Ternant, A Aubourg, C Magdelaine-Beuzelin, D Degenne, H Watier, L Picon and G Paintaud.

Faculty of medicine, Université François Rabelais, Tours, France

Objectives: Infliximab, an anti-TNF-α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective of this study was to assess the influence of antibodies directed towards infliximab (ATI) on infliximab pharmacokinetics.

Methods: Thirty-three chronic inflammatory bowel disease patients in whom infliximab concentration and ATI were monitored on a routine basis, using ELISA techniques, were included. Infliximab pharmacokinetics was analyzed using a population two-compartment pharmacokinetic model. Influence of sex, weight, age, disease, concomitant immunosuppressive treatment and ATI on the parameters was investigated.

Results: In 5 out of 33 patients, ATI were detected at least once during their follow-up. Mean systemic clearance of infliximab with and without ATI was 0.012 and 0.032 L/h, respectively (p < 0.001). Mean distribution half-life (t½-α) with and without ATI was 4.3 and 2.5 days, respectively (p = 0.015). Mean elimination half-life (t½-β) with and without ATI was 12.4 and 18.8 days, respectively (p = 0.002). In 2 patients, an increase in dose led to a decrease in infliximab clearance, suggesting that the influence of ATI may be neutralized by dose adjustment.

Conclusions: These results describe for the first time the quantitative influence of ATI on infliximab clearance. The monitoring of ATI may help to understand failures of infliximab treatment and may guide dose adjustment.

Reference: PAGE 17 (2008) Abstr 1364 [www.page-meeting.org/?abstract=1364]
Poster: Applications- Biologicals/vaccines