title: 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.
abstract: 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.
authors.affiliation: *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.
authors.forename: Alicia
authors.initials: A
authors.lastname: Algaba
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Linares
authors.forename: M
authors.initials: M
authors.lastname: Encarnación Fernández-Contreras
authors.forename: Ariadna
authors.initials: A
authors.lastname: Figuerola
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvet
authors.forename: Iván
authors.initials: I
authors.lastname: Guerra
authors.forename: Inés
authors.initials: I
authors.lastname: de Pousa
authors.forename: María
authors.initials: M
authors.lastname: Chaparro
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.forename: Fernando
authors.initials: F
authors.lastname: Bermejo
mesh_terms: D000068879:Adalimumab; D000328:Adult; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000188:drug therapy; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D042787:Receptor, TIE-2 / Q000097:blood; D012074:Remission Induction; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000069285:Infliximab; D042787:Receptor, TIE-2; D000068879:Adalimumab