title: Long-Term Outcome of Patients with Ulcerative Colitis and Primary Non-response to Infliximab.
abstract: OBJECTIVE
  We studied the long-term outcome of patients with ulcerative colitis [UC] and primary non response [PNR] to infliximab and searched for predictors of colectomy in these patients.
  
  
  METHODS
  This retrospective, multi-centre study included UC patients from three European referral centres, with PNR to infliximab defined as a lack of clinical improvement after the induction therapy, leading to drug discontinuation. Relapse, for patients who continued on biologicals after PNR to infliximab, was defined as drug discontinuation for PNR, loss of response, or serious adverse event. Serum infliximab concentrations at Weeks 2 and 6 were evaluated using an enzyme-linked immunosorbent assay [ELISA] developed in house.
  
  
  RESULTS
  The study population consisted of 99 anti-tumour necrosis factor [TNF]-naïve patients with UC and PNR to infliximab. At the end of follow-up (median: 3.2 [interquartile range 1-6.3] years), 55 [55.6%] of these patients underwent colectomy. Multiple Cox regression analysis identified acute severe UC (hazard ratio [HR]: 24; 95% confidence interval [CI]: 2.5-231; p = 0.006], baseline C-reactive protein [CRP] > 5mg/l [HR: 11; 95% CI: 2.1-58.8; p = 0.005], baseline albumin < 40g/l [HR: 9.5; 95% CI: 1.3-71.4; p = 0.026], and infliximab concentration at Week 2 < 16.5 μg/ml [HR: 5.6; 95% CI: 1.1-27.8; p = 0.034] as independent predictors of colectomy. Regarding patients who continued on biologicals after PNR to infliximab, there was a marginally higher cumulative probability for relapse in patients switching to another anti-TNF agent compared with those swapping to vedolizumab [p logrank = 0.08].
  
  
  CONCLUSIONS
  About half of UC patients with PNR to infliximab will undergo colectomy. Patients with severe inflammation and low serum infliximab concetrations during the induction phase are at greatest risk.
authors.affiliation: KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium Evangelismos Hospital, Department of Gastroenterology, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papamichael
authors.affiliation: Nancy University Hospital, Inserm U954 and Department of Gastroenterology, Nancy, France.
authors.forename: Oliviane
authors.initials: O
authors.lastname: Rivals-Lerebours
authors.affiliation: KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Billiet
authors.affiliation: KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Leuven, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
authors.affiliation: KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.affiliation: KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rutgeerts
authors.affiliation: Evangelismos Hospital, Department of Gastroenterology, Athens, Greece.
authors.forename: Gerassimos J
authors.initials: GJ
authors.lastname: Mantzaris
authors.affiliation: Nancy University Hospital, Inserm U954 and Department of Gastroenterology, Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: KU Leuven, Translational Research Center for Gastrointestinal Disorders, and University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium severine.vermeire@uzleuven.be.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
mesh_terms: D000328:Adult; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy; D000069285:Infliximab / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure
chemical_list: D005765:Gastrointestinal Agents; D000069285:Infliximab
keywords: Drug concentrations; infliximab; primary non-response; ulcerative colitis