title: Long-term outcome of patients with Crohn's disease who discontinued infliximab therapy upon clinical remission.
abstract: OBJECTIVE
  There are limited data on the effects of discontinuing infliximab therapy for Crohn's disease (CD). We investigated the long-term outcome of patients with CD who discontinued infliximab while in clinical remission, and searched for prognostic markers of continued remission after infliximab cessation.
  
  
  METHODS
  We performed a retrospective, single-center study of 100 patients with CD who discontinued infliximab upon achieving clinical remission; 84 patients continued immunomodulator therapy. Clinical and endoscopic data were retrieved from a medical database in Belgium, and patients were followed up through April 2013 (median, 9.7 y; interquartile range, 8-11.5 y). Sustained clinical remission (SCR) was defined as maintenance of disease remission, without escalation in medical therapy or CD-related surgeries, until the end of the follow-up period. We measured trough concentrations of infliximab, antibodies to microbial antigens, and circulating inflammatory markers in serum samples collected before treatment and at the time of infliximab discontinuation.
  
  
  RESULTS
  At the end of the follow-up period, 52 patients had SCR. Univariate (log-rank) analysis associated SCR with patient age at diagnosis (≥25 y; P = .012) and disease duration (<1 y; P = .017). Among factors evaluated at the time of infliximab discontinuation, infliximab trough concentrations (<6 μg/mL; P = .031), complete mucosal healing (P = .046), and serum positivity for vascular cell adhesion molecule-1 (>0.67 μg/mL; P = .024) were associated with SCR. In multiple Cox proportional hazards regression analysis, only age at diagnosis of 25 years and older was associated independently with SCR (hazard ratio, 1.83; 95% confidence interval, 1.03-3.25; P = .04).
  
  
  CONCLUSIONS
  In a large, real-life study, 52% of patients with CD who discontinued infliximab upon achieving clinical remission remained in SCR after a median period of approximately 10 years; Most patients remained on immunomodulator therapy. Although patients with CD have variable responses to infliximab, a subgroup achieved long-term remission after infliximab discontinuation.
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium; Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papamichael
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tops
authors.affiliation: Prometheus Therapeutics and Diagnostics, Laboratories, Inc, San Diego, California.
authors.forename: Scott
authors.initials: S
authors.lastname: Hauenstein
authors.affiliation: Prometheus Therapeutics and Diagnostics, Laboratories, Inc, San Diego, California.
authors.forename: Sharat
authors.initials: S
authors.lastname: Singh
authors.affiliation: Prometheus Therapeutics and Diagnostics, Laboratories, Inc, San Diego, California.
authors.forename: Fred
authors.initials: F
authors.lastname: Princen
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium. Electronic address: marc.ferrante@zuleuven.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
mesh_terms: D000293:Adolescent; D000328:Adult; D001530:Belgium; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D000069285:Infliximab / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry; D016896:Treatment Outcome; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D018836:Inflammation Mediators; D000069285:Infliximab
keywords: Anti-TNF Agent; Anti–Tumor Necrosis Factor; Inflammatory Bowel Disease; Prognosis; Serology; VCAM