title: Repeated intensified infliximab induction - results from an 11-year prospective study of ulcerative colitis using a novel treatment algorithm.
abstract: BACKGROUND
  Anti-tumour necrosis factor (TNF) agents play a pivotal role in the treatment of moderate to severe ulcerative colitis (UC), and yet, no international consensus on when to discontinue therapy exists.
  
  
  OBJECTIVE
  The aim of this study is to study the long-term performance of a treatment algorithm of repeated intensified induction therapy with infliximab (IFX) to remission, followed by discontinuation in patients with UC.
  
  
  METHODS
  Patients with moderate to severe UC were enroled in an open prospective study design. The following algorithm was implemented: (a) intensified induction treatment to remission (Ulcerative Colitis Disease Activity Index score 0-2); (b) discontinuation of IFX; and (c) reinduction treatment if relapse. Mucosal gene expression for TNF was measured with qPCR.
  
  
  RESULTS
  A total of 116 patients were included. The median observation time was 47 and 51 months in intention to treat and per protocol. Remission rates of the first three inductions were 95, 93 and 91% per protocol and 83, 56 and 59% by intention to treat. The median time in remission was 40 months per protocol and 34 months by intention to treat. Long-term remission without further anti-TNF treatment during the observation period was obtained for 41%, with a median observation time of 48 months (range: 18-129 months). The median time to relapse was 33 and 11 months with/without normalization of mucosal TNF, respectively. The 5-year success rate for maintaining the effect of IFX in the algorithm was 66%.
  
  
  CONCLUSIONS
  The treatment algorithm is highly effective for achieving long-term clinical remission in UC. Normalization of mucosal TNF gene expression predicts long-term remission upon discontinuation of IFX.
authors.affiliation: aResearch Group of Gastroenterology and Nutrition, Department of Clinical Medicine, University of Tromsø bDepartment of Nephrology and Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø cDepartment of Medicine, Telemark Hospital, Skien dDepartment of Medicine, Division of Hammerfest, Finnmark Hospital, Hammerfest, Norway.
authors.forename: Kay-Martin
authors.initials: KM
authors.lastname: Johnsen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Goll
authors.forename: Vegard
authors.initials: V
authors.lastname: Hansen
authors.forename: Trine
authors.initials: T
authors.lastname: Olsen
authors.forename: Renathe
authors.initials: R
authors.lastname: Rismo
authors.forename: Richard
authors.initials: R
authors.lastname: Heitmann
authors.forename: Mona D
authors.initials: MD
authors.lastname: Gundersen
authors.forename: Jan M
authors.initials: JM
authors.lastname: Kvamme
authors.forename: Eyvind J
authors.initials: EJ
authors.lastname: Paulssen
authors.forename: Hege
authors.initials: H
authors.lastname: Kileng
authors.forename: Knut
authors.initials: K
authors.lastname: Johnsen
authors.forename: Jon
authors.initials: J
authors.lastname: Florholmen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000276:immunology; D019091:Critical Pathways; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D060828:Induction Chemotherapy; D000069285:Infliximab / Q000008:administration & dosage* / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009664:Norway; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab