title: A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis.
abstract: OBJECTIVE
  Infliximab is effective for patients with refractory ulcerative colitis (UC), but few factors have been identified that predict long-term outcome of therapy. We aimed to identify a panel of markers associated with outcome of infliximab therapy to help physicians make personalized treatment decisions.
  
  
  METHODS
  We collected data from the first 285 patients with refractory UC (41% female; median age, 39 y) treated with infliximab before July 2012 at University Hospitals Leuven, in Belgium. We performed a Cox regression analysis to identify independent factors that predicted relapse-free and colectomy-free survival, and used these factors to create a panel of markers (risk panel).
  
  
  RESULTS
  During a median follow-up period of 5 years, 61% of patients relapsed and 20% required colectomy. Independent predictors of relapse-free survival included short-term complete clinical response (odds ratio [OR], 3.75; 95% confidence interval [CI], 2.35-5.97; P < .001), mucosal healing (OR, 1.87; 95% CI, 1.17-2.98; P = .009), and absence of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) (OR, 1.96; 95% CI, 1.23-3.12; P = .005). Independent predictors of colectomy-free survival included short-term clinical response (OR, 7.74; 95% CI, 2.76-21.68; P < .001), mucosal healing (OR, 4.02; 95% CI, 1.16-13.97; P = .028), baseline level of C-reactive protein (CRP) of 5 mg/L or less (OR, 2.95; 95% CI, 1.26-6.89; P = .012), and baseline level of albumin of 35 g/L or greater (OR, 3.03; 95% CI, 1.12-8.22; P = .029). Based on serologic analysis of a subgroup of 112 patients, levels of infliximab greater than 2.5 μg/mL at week 14 of treatment predicted relapse-free survival (P < .001) and colectomy-free survival (P = .034). A risk panel that included levels of pANCA, CRP, albumin, clinical response, and mucosal healing identified patients at risk for UC relapse or colectomy (both P < .001).
  
  
  CONCLUSIONS
  Clinical response and mucosal healing were confirmed as independent predictors of long-term outcome from infliximab therapy in patients with UC. We identified additional factors (levels of pANCA, CRP, and albumin) to create a risk panel that predicts long-term outcomes of therapy. Serum levels of infliximab at week 14 of treatment also were associated with patient outcomes. Our risk panel and short-term serum levels of infliximab therefore might be used to guide therapy.
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Maria Theresa
authors.initials: MT
authors.lastname: Arias
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Abdominal Surgery, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Anthony
authors.initials: A
authors.lastname: de Buck van Overstraeten
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Billiet
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Baert
authors.affiliation: Department of Abdominal Surgery, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Albert
authors.initials: A
authors.lastname: Wolthuis
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Maja
authors.initials: M
authors.lastname: Noman
authors.affiliation: Department of Pediatrics, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Hoffman
authors.affiliation: Department of Abdominal Surgery, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Andre
authors.initials: A
authors.lastname: D'Hoore
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, KU Leuven-University of Leuven, Leuven, Belgium. Electronic address: marc.ferrante@uzleuven.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001530:Belgium; D015415:Biomarkers / Q000032:analysis; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044967:Serum / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007155:Immunologic Factors; D000069285:Infliximab
keywords: Biomarker; Drug; Prognostic Factor; Response To Therapy