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The Effects of Infliximab or Adalimumab on Vascular Endothelial Growth Factor and Angiopoietin 1 Angiogenic Factor Levels in Inflammatory Bowel Disease: Serial Observations in 37 Patients

Algaba, Alicia MSc*; Linares, Pablo M. MSc†,‡; Encarnación Fernández-Contreras, M. PhD, MD†,‡; Figuerola, Ariadna MSc§,‖; Calvet, Xavier PhD, MD§,‖; Guerra, Iván MD*; de Pousa, Inés PhD, MD†,‡; Chaparro, María PhD, MD†,‡; Gisbert, Javier P. PhD, MD†,‡; Bermejo, Fernando PhD, MD*

doi: 10.1097/MIB.0000000000000004
Original Basic Science Articles

Background: Infliximab and adalimumab effectiveness might be related with changes in angiogenic factors. The aim of the study was to compare the concentrations of angiogenic proteins in patients with inflammatory bowel disease (IBD) and healthy controls and to analyze changes in the levels during infliximab and adalimumab treatment.

Methods: A prospective case–control study was conducted in 37 patients with IBD starting treatment with infliximab (16 with Crohn’s disease and 6 with ulcerative colitis) or adalimumab (15 with Crohn’s disease) and 40 control subjects. Four samples were taken from IBD patients, one before each of the first 3 doses of infliximab/adalimumab and one at week 14. Serum levels of vascular endothelial growth factor (VEGF), placental growth factor, angiopoietin 1 (Ang1), angiopoietin 2, and Tie2 were measured using enzyme-linked immunosorbent assay.

Results: Patients with IBD had higher VEGF levels than control subjects (511.5 ± 255.6 versus 395.5 ± 256.4; P = 0.05). Patients who achieved remission at the third dose of anti–TNF-alpha had lower VEGF levels at baseline (453.5 ± 250.7 versus 667.5 ± 153.9 pg/mL) and before the second (409.7 ± 217 versus 681.3 ± 350.6 pg/mL) and third (400.5 ± 222.8 versus 630.4 ± 243.1 pg/mL) doses compared with those with no remission (P < 0.05). Ang1 levels decreased before each treatment dose in patients who achieved remission (P < 0.05). High baseline VEGF levels predicted for a poor response to anti–TNF-alpha therapy (area under the receiver operating characteristics curve = 0.8), whereas high Ang1 levels were associated with disease remission (area under the receiver operating characteristics curve = 0.7). Concentrations of angiogenic proteins did not correlate with clinical activity scores.

Conclusions: Circulating VEGF and Ang1 levels decrease after anti–TNF-alpha therapy and may predict response to treatment. Whether these changes are a direct effect of anti–TNF-alpha therapy or a sign of disease improvement remains to be elucidated.

Article first Published online 20 February 2014

*Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain;

Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain;

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain;

§Gastroenterology Unit, Hospital de Sabadell, Institut Parc Taulí, Sabadell, Barcelona, Spain; and

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.

Reprints: Alicia Algaba, MSc, C/Isaac Peral, 43. Bloque D1, 1ºB, 28330, San Martín de la Vega, Madrid, Spain (e-mail:

The authors have no conflicts of interest to disclose.

A. Algaba and P. B. Linares contributed equally to this study and should be considered as first coauthors.

Supported by grants from the Instituto de Salud Carlos III (P.M.L.: PS02369), Ministerio de Economía y Competitividad, Spain, and from AbbVie Laboratories (A.A.). A. Algaba and F. Bermejo received grant from MSD. F. Bermejo received consultancy fee from AbbVie, and received payment for development of educational presentations from MSD and AbbVie.

Received December 07, 2013

Accepted January 19, 2014

© Crohn's & Colitis Foundation of America, Inc.
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