title: Five-year Safety Data From ENCORE, a European Observational Safety Registry for Adults With Crohn's Disease Treated With Infliximab [Remicade®] or Conventional Therapy.
abstract: OBJECTIVE
  The ENCORE registry aimed at comparing the long-term safety of Crohn's disease [CD] treatment with infliximab [Remicade®] and with conventional therapies in real-world clinical practice.
  
  
  METHODS
  The 5-year, prospective, observational ENCORE registry followed patients with CD in nine European countries, who received treatment with infliximab, conventional therapies, or switched to infliximab from conventional therapy. Adverse events [AEs] in pre-specified categories and serious AEs were recorded at least every 6 months of the 5-year observation period. Frequency of events was evaluated, and multivariable analyses using follow-up time [Cox proportion hazards model] and exposure time [Poisson regression] were used to identify risk factors for time to AEs in pre-specified categories.
  
  
  RESULTS
  Patients who received infliximab [N = 1541], conventional therapies [N = 1121], or switched to infliximab [N = 298] were followed for medians of 60.4, 55.6, and 42.5 months, respectively. Infliximab median exposure was 18.7 and 19.3 months in the infliximab and switched-to-infliximab groups, respectively. In time-to-event Cox proportion hazards [PH] analyses adjusting for confounders, infliximab [vs conventional therapy] was associated with serious infections (hazard ratio [HR] = 1.64, 95% confidence interval [CI]: 1.17, 2.31] and haematological conditions [HR = 2.91, CI: 1.51, 5.59], and not associated with lymphoproliferative disorders/malignancy [HR = 1.44, CI: 0.86, 2.42] or death [HR = 1.22, CI: 0.63, 2.36]. Prednisone use was associated with higher mortality [HR = 3.58, CI: 1.49, 8.61]. In exposure-adjusted Poisson regression analyses, infliximab was associated with lower mortality (risk ratio [[RR] 0.39, CI: 0.17, 0.88]).
  
  
  CONCLUSIONS
  Data from 5-year safety follow-up of patients with CD in the ENCORE registry demonstrate that infliximab [Remicade®] exposure is associated with increased risk of serious infections and haematological conditions, whereas mortality may be decreased.
authors.affiliation: Department of Gastroenterology, Academic MedicalCenter, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Klinische Abt. Gastroenterologie & Hepatologie, Medical University, Vienna, Austria and McMaster University, Hamilton, ON, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Department of Gastroenterology, Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Panes
authors.affiliation: Department of Gastroenterology, University of Calgary, Calgary, AB, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Gastroenterology, A.O. San Camillo Forlanini, Rome, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Prantera
authors.affiliation: Department of Gastroenterology, Lund University, University Hospital Skane, Malmö, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lindgren
authors.affiliation: Centre for Inflammatory Bowel Diseases, Univerisity of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
authors.affiliation: Centre for Biostatistics, Merck Inc., Kenilworth, NJ, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Centre for Biostatistics, Merck Inc., Kenilworth, NJ, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Boice
authors.affiliation: Centre for Biostatistics, Merck Inc., Kenilworth, NJ, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Huyck
authors.affiliation: Global Medical Affairs, MSD International GmbH, Lucerne, Switzerland.
authors.forename: Freddy
authors.initials: F
authors.lastname: Cornillie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D001379:Azathioprine / Q000009:adverse effects; D003424:Crohn Disease / Q000188:drug therapy*; D003711:Demyelinating Diseases / Q000139:chemically induced; D057915:Drug Substitution; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects*; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007239:Infections / Q000139:chemically induced*; D000069285:Infliximab / Q000009:adverse effects*; D007262:Infusions, Intravenous / Q000009:adverse effects; D008232:Lymphoproliferative Disorders / Q000139:chemically induced; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects; D019804:Mesalamine / Q000009:adverse effects; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D009026:Mortality; D009294:Narcotics / Q000009:adverse effects; D011241:Prednisone / Q000009:adverse effects; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D012460:Sulfasalazine / Q000009:adverse effects; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D009294:Narcotics; D012460:Sulfasalazine; D019804:Mesalamine; D000069285:Infliximab; D015122:Mercaptopurine; D001379:Azathioprine; D011241:Prednisone; D008727:Methotrexate
keywords: Clinical trials; Quality of life