title: Does fecal calprotectin predict short-term relapse after stopping TNFα-blocking agents in inflammatory bowel disease patients in deep remission?
abstract: OBJECTIVE
  This prospective multicenter study examined whether elevated fecal calprotec tin (FC) concentrations after stopping TNFα-blocking therapy can predict clinical or endoscopic relapse. In addition, we evaluated the impact of histological remission on the relapse risk.
  
  
  METHODS
  We enrolled inflammatory bowel disease (IBD) patients who were in clinical, endoscopic, and FC-based (< 100 μg/g) remission after a minimum 11 months of TNFα-blocking therapy. The patients were followed-up for 12 months after the discontinuation of TNFα-blocking therapy. FC was collected monthly for the first 6 months and thereafter every second month. Ileocolonoscopy was performed at inclusion, at 4 months, at the study end, and at the time of clinical relapse.
  
  
  RESULTS
  Of 52 enrolled patients, 49 (16 Crohn's disease, 33 ulcerative colitis/IBD unclassified) provided the stool samples requested and comprised the study group. During the follow-up, 15/49 (31%) relapsed, whereas 34 (69%) remained in remission. Patients relapsing showed constantly elevated FC levels for a median of 94 (13-317) days before the relapse. Significant increase in median FC levels was seen 2 (p = 0.0014), 4 (p = 0.0056), and 6 (p = 0.0029) months before endoscopic relapse. Constantly normal FC concentrations during the follow-up were highly predictive for clinical and endoscopic remission. Normal FC concentrations in patients with remission were associated with histological remission.
  
  
  CONCLUSIONS
  FC seems to increase and remain elevated before clinical or endoscopic relapse, suggesting that it can be used as a surrogate marker for predicting and identifying patients requiring close follow-up in clinical practice.
authors: Maria Helsinki City Hospital and University of Helsinki, Helsinki, Finland pauliina.molander@welho.com.
authors: Pauliina
authors: P
authors: Molander
authors: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland University of Helsinki, Institute of Clinical Medicine, Department of Medicine, Division of Gastroenterology, Helsinki, Finland.
authors: Martti
authors: M
authors: Färkkilä
authors: Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors: Ari
authors: A
authors: Ristimäki
authors: Department of Medicine, Division of Gastroenterology, Turku University Central Hospital, Turku, Finland.
authors: Kimmo
authors: K
authors: Salminen
authors: Department of Medicine, Division of Gastroenterology, Turku University Central Hospital, Turku, Finland.
authors: Helena
authors: H
authors: Kemppainen
authors: Department of Medicine, Division of Gastroenterology, Oulu University Central Hospital, Oulu, Finland.
authors: Timo
authors: T
authors: Blomster
authors: Department of Medicine, Division of Gastroenterology, Oulu University Central Hospital, Oulu, Finland.
authors: Ritva
authors: R
authors: Koskela
authors: Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
authors: Airi
authors: A
authors: Jussila
authors: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Jorvi Hospital, Espoo, Finland.
authors: Henna
authors: H
authors: Rautiainen
authors: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Peijas Hospital, Vantaa, Finland.
authors: Markku
authors: M
authors: Nissinen
authors: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.
authors: Johanna
authors: J
authors: Haapamäki
authors: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.
authors: Perttu
authors: P
authors: Arkkila
authors: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.
authors: Urpo
authors: U
authors: Nieminen
authors: Department of Medicine, Hyvinkää Hospital, Hyvinkää, Finland.
authors: Juha
authors: J
authors: Kuisma
authors: Department of Medicine, Porvoo Hospital, Porvoo, Finland.
authors: Jari
authors: J
authors: Punkkinen
authors: Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland University of Helsinki, Institute of Clinical Medicine, Department of Medicine, Division of Gastroenterology, Helsinki, Finland.
authors: Kaija-Leena
authors: KL
authors: Kolho
authors: Helsinki University Central Hospital, Department of Surgery, Biomedicum Helsinki, Finland.
authors: Harri
authors: H
authors: Mustonen
authors: Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.
authors: Taina
authors: T
authors: Sipponen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003113:Colonoscopy; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry*; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D039841:Leukocyte L1 Antigen Complex; D014409:Tumor Necrosis Factor-alpha
keywords: Crohn’s disease; Fecal biomarkers; Histology; TNFα-blocking therapy; Ulcerative colitis