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P042. The effect of infliximab and adalimumab treatment on angiogenic factor levels in patients with inflammatory bowel disease (IBD)

A. Algaba1, P.M. Linares2, M.E. Fernández-Contreras2, A. Figuerola3, X. Calvet3, I. Guerra1, J.C. Villa1, M. Chaparro2, J.L. Rodríguez-Agulló1, J.P. Gisbert2, F. Bermejo1

1Hospital Universitario de Fuenlabrada, Gastroenterology, Fuenlabrada, Spain; 2Hospital Universitario de La Princesa-IP, Gastroenterology and CIBERHED, Madrid, Spain; 3Hospital de Sabadell. Institut Universitari Parc Taulí, Gastroenterology and CIBERHED, Sabadell, Spain

Background: Effectiveness of infliximab (IFX) and adalimumab (ADA) treatment could be related to the modification of different angiogenic proteins (AP), VEGF, PlGF, Ang1 and Ang2 and their receptor Tie2. Our aim was to compare the concentrations of these AP in patients with IBD and healthy controls and to analyze their modifications during IFX and ADA treatment.

Methods: Prospective and case–control study in healthy controls and patients with IBD that initiate treatment with IFX or with ADA. One serum sample from each control was obtained. Four samples were obtained from each IBD patient previous to each of the first 3 doses of IFX (week 0, 2, 6) or ADA (week 0, 2, 4) and at week 14. AP serum concentrations were determined by ELISA. Ulcerative colitis (UC) and Crohn disease (CD) activity was ascertained by CDAI and modified Truelove-Witts indexes, respectively. Clinical response: decrease of at least five points in the Truelove-modified index, or of at least 70 points of CDAI index. Clinical remission: reduction to a score below 11 points in the modified Truelove-Witts index, or below 150 points in the CDAI index.

Results: 40 controls and 41 patients with IBD that initiate treatment with IFX (19 CD, 6 UC) or with ADA (15 CD, 1 UC) were included. 70% of patients were in concomitant treatment with corticoids and 77% with thiopurines. In 66.7% of cases there was response to IFX/ADA therapy. At week 14, 72% of patients were in clinical remission. No significant differences of AP serum concentrations between patients with IBD and controls were found. Apart from PlGF (p < 0.05), concentrations of VEGF, Ang1, Ang2 and Tie2, were unchanged during treatment with IFX/ADA. There were no significant differences between CD and ulcerative colitis, IFX and ADA treatment or between responders and non-responders to IFX/ADA treatment.

*Significant differences (p < 0.05) respect to pre-treatment values.
 VEGF (pg/ml)PlGF (pg/ml)Ang1 (ng/ml)Ang2 (ng/ml)Tie2 (ng/ml)
2nd dose477±26515.3±1040.6±19.43.2±1.923±6.8
3rd dose451.5±247.814.6±9.539.3±18.33±224±6.6
Week 14434.4±233.412±6 *37.5±14.73.2±1.724.7±8.3

Conclusions: PlGF serum levels and it pro-inflammatory activity seem to be down-regulated by antiTNF therapy. Nevertheless, the effectiveness of IFX and ADA treatment is not be related to modifications in the concentrations of the other angiogenic factors (VEGF, Ang1, Ang2 and Tie2).