title: Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis.
abstract: OBJECTIVE
  Mucosal healing is an independent predictor of sustained clinical remission in patients with ulcerative colitis (UC) treated with infliximab. We investigated whether infliximab concentrations during induction therapy are associated with short-term mucosal healing (STMH) in patients with UC.
  
  
  METHODS
  We performed a retrospective, single-center analysis of data collected from a tertiary referral center from 101 patients with UC who received scheduled induction therapy with infliximab at weeks 0, 2, and 6 and had an endoscopic evaluation at baseline and after induction therapy. STMH was defined as Mayo endoscopic sub-score ≤1, assessed at weeks 10-14, with baseline sub-score ≥2. Infliximab concentrations were evaluated in serum samples collected at weeks 0, 2, 6, and 14 of infliximab therapy by using an enzyme-linked immunosorbent assay we developed.
  
  
  RESULTS
  Fifty-four patients (53.4%) achieved STMH. Patients with STMH had a higher median infliximab concentration at weeks 2, 6, and 14 than patients without STMH. A receiver operating characteristic (ROC) analysis identified infliximab concentration thresholds of 28.3 (area under the ROC curve [AUROC], 0.638), 15 (AUROC, 0.688), and 2.1 μg/mL (AUROC, 0.781) that associated with STMH at weeks 2, 6, and 14, respectively. Multiple logistic regression analysis identified infliximab concentration ≥15 at week 6 (P = .025; odds ratio, 4.6; 95% confidence interval, 1.2-17.1) and ≥2.1 μg/mL at week 14 (P = .004; odds ratio, 5.6; 95% confidence interval, 1.7-18) as independent factors associated with STMH.
  
  
  CONCLUSIONS
  In an analysis of data from real-life clinical practice, we associated infliximab concentrations during the induction therapy with STMH in patients with UC.
authors.affiliation: KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium; KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papamichael
authors.affiliation: KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Van Stappen
authors.affiliation: KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
authors.affiliation: KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Billiet
authors.affiliation: KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tops
authors.affiliation: KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Claes
authors.affiliation: KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), and University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium. Electronic address: marc.ferrante@uzleuven.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000473:pathology*; D004724:Endoscopy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000069285:Infliximab / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry; D062606:Tertiary Care Centers; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000069285:Infliximab
keywords: Anti-TNF Agent; Antibodies to Infliximab; Mucosal Healing; Ulcerative Colitis