title: First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis-results from a multicenter prospective randomized controlled trial and its post hoc analysis.
abstract: BACKGROUND
  Infliximab (IFX) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis (UC). A high serum trough level of IFX (TL) is reported to be associated with sustained efficacy during maintenance treatment. As part of a phase 3 randomized controlled trial of IFX in UC, we assessed the predictive value of the first TL at week 2 for short- and long-term response.
  
  
  METHODS
  Patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Post hoc analysis was then performed for TL and clinical outcomes.
  
  
  RESULTS
  Clinical response rate at week 8, the primary end point, was significantly higher in the IFX group than placebo (p = 0.005). The incidence of adverse events between groups was similar. Week 2 TL was significantly associated with a 14-week clinical activity index (CAI) remission. In multiple logistic regression analysis, the week 2 TL-to-CAI ratio (TL/CAI, odds ratio 8.07; 95% confidence interval 2.84-27.07, p < 0.001) was an independent factor correlating with 14-week CAI remission. The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing.
  
  
  CONCLUSIONS
  IFX was confirmed to be effective and safe in this population. Our results suggest that the first TL at week 2, in combination with clinical evaluation, is useful for predicting both short- and long-term outcomes, allowing an earlier decision between continuing IFX or switching to other options.
authors.affiliation: Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Inflammatory Bowel Diseases Center, Sapporo-kosei General Hospital, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Motoya
authors.affiliation: Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Hirai
authors.affiliation: Center for Diagnostic and Therapeutic Endoscopy, Keio University, School of Medicine, Tokyo, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ogata
authors.affiliation: Digestive Disease Center, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Osaka, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Osaka, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan. thibi@insti.kitasato-u.ac.jp.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D000069285:Infliximab
keywords: Infliximab; Mucosal healing; Primary response; Therapeutic drug monitoring; Ulcerative colitis