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P501 High TNF-production of CD14+ cells and short disease duration are independent predictive factors for response to Infliximab treatment

D. Lissner*1, B. Jessen1,2, E. Sonnenberg1, M. Schumann1, F. Schmidt1, Y. Rodriguez Sillke1, B. Siegmund1

1Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Department for Medicine (Gastroenterology, Infectious diseases, Rheumatology), Berlin, Germany, 2Berlin Institute of Health, Berlin, Germany

Background

A substantial rate of primary non-response to Infliximab in patients with inflammatory bowel disease (IBD) together with the increasing availability of alternative biologics emphasise the need for predictive markers to personalize treatment. Thus, the study’s aim was to identify predictive factors for response to Infliximab treatment.

Methods

21 patients with Crohn’s disease (CD) and 20 patients with ulcerative colitis (UC) without treatment with biologicals in the past 6 months were prospectively included into this observational study before their first Infliximab infusion. Harvey–Bradshaw-Index (HBI) or partial Mayo Score (pMS), C-reactive protein (CRP) and ultrasound (Limberg Score) served to quantify disease activity at baseline and Week 6, respectively. Cytokine production of LPS-stimulated PBMCs at baseline (TNF, IL-1, IL-6, IL-8, IL-10, IL-12p70) were measured by ELISA, CBA and flow cytometry. A ROC analysis for TNF-production was applied to estimate a cut-off to group patients into either low or high TNF-producers. Primary endpoint was clinical response defined as a decline in score of ≥ 2 (HBI) or ≥ 3 (pMS) at Week 6, secondary endpoints were decrease in CRP or Limberg score at Week 6. The need for urgent colectomy within the 6 weeks was defined as non-response. Mann–Whitney U and χ2 test served for univariate analysis and logistic regression was used for multi-variate analysis.

Results

41 patients (48.8% females) with a mean age of 38 (SD 12.8) were included in the analysis. Of these, 30 patients (73.2%) responded to Infliximab treatment. Responders had shorter disease duration (p = 0.018), higher Limberg score at baseline (p = 0.021) and produced significantly more TNF (p = 0.049) and IL-6 (p = 0.028) at baseline compared with non-responders. Flow-cytometry identified CD14+ cells as the main TNF-producers. For TNF-production, ROC analysis of all IBD-patients revealed a cut-off value of 500 pg/ml having a sensitivity of 82% and specificity of 78% to predict response, which was much stronger when analysing only CD patients (sensitivity of 100% and specificity of 82%). Low TNF-producers were 14.8 times more likely to have a treatment failure, compared with high TNF-producers (OR 14.8, 2.6–85.1, p = 0.003). Multi-variate analysis including all significant factors of the univariate analysis identified high TNF-production at baseline (p = 0.005) and shorter disease duration (p = 0.028) as independent predictors for response to Infliximab.

Conclusion

High TNF-production of CD14+ cells at baseline and shorter disease duration were independent factors to predict response to Infliximab in IBD patients.