P599 Azathioprine in the prevention of anti-infliximab antibody formation: A pilot dose-finding study

Kojecký, V.(1,2);Wasserbauer , M.(3);Keil, R.(3);

(1)Masaryk University, Faculty of Medicine, Brno, Czech Republic;(2)Bata regional hospital, Department of Internal medicine, Zlin, Czech Republic;(3)Charles University in Prague and Motol University Hospital, Department of Internal Medicine, Prague, Czech Republic;


The infliximab (IFX) therapy is associated with production of the anti-IFX antibodies (ATI), that can lead to infusion reactions and affect the therapeutic response. Concomitant use of azathioprine (AZA) in patients treated with IFX is recommended. A lower dosage is suggested however without further specification. The aim of this study is to determine the threshold dose of AZA to prevent ATI formation during IFX therapy.


The Retrospective, multicenter (Zlin, Prague, Czech rep.), observational study. The adult patients with ulcerative colitis or Crohn's disease, treated with IFX in scheduled regimen (5mg/kg á 8 weeks), on concomitant azathioprine therapy (> 3 month), without any other immunomodulator or steroids, who were tested for IFX and ATI levels, were enrolled. The primary outcome measure was the dose of AZA and ATI positivity (cut-off > 3 AU/ml), secondary measure included interval to the appearance of ATI. ROC analysis was used to evaluate AZA dose and interval predictive of the ATI positivity.


Of the 62 patients analyzed (53% female, mean age 34.1 years), 76% had Crohn's disease. 29 (47%) subjects were treated with biosimilar IFX. The mean dose of AZA was 1.5 ± 0.5 mg/kg, and the duration of IFX treatment was 44.2 ± 41.4 months. ATI ´s were present in 23 subjects (37.1%), with no difference between original and biosimilar IFX. ATI positivity was associated with lower mean IFX levels (1.8 ± 2.4 vs 6.0 ± 5.1ug/ml, p=0.002).   The threshold dose of AZA for ATI positivity was predicted to 1.2 mg/kg (95% CI 0.6-1.8, p=0.02, AUC 0.682) and the time to antibody appearance to 13.0 months (95% CI 5.0-49.1, p=0.02, AUC 0.672).


The dose of AZA lower than 1.2 mg/kg was associated with a higher chance of anti-IFX antibodies development. Their  appearance may be expected after 1 year from the initiation of the combo IFX therapy. ATI´s are associated with reduced IFX through levels.