title: Drug therapies and the risk of malignancy in Crohn's disease: results from the TREAT™ Registry.
abstract: OBJECTIVE
  We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined.
  
  
  METHODS
  Utilizing data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT™) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, influences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95 % confidence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA).
  
  
  RESULTS
  As of 23 February 2010, 6,273 CD patients (infliximab during registry=3,420 (during or within 1 year before registry=3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab- and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR)=1.59/10 years; P<0.001), disease duration (HR=1.64/10 years; P=0.012), and smoking (HR=1.38; P=0.045) but neither immunosuppressive therapy alone (HR=1.43; P=0.11), infliximab therapy alone (HR=0.59; P=0.16), nor their combination (HR=1.22, P=0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio=4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither.
  
  
  CONCLUSIONS
  In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lichtenstein
authors.affiliation: Robarts Clinical Trials, Inc.; Departments of Medicine, Epidemiology & Biostatistics; University of Western Ontario, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, Chicago, Illinois, USA.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Cohen
authors.affiliation: Atlanta Gastroenterology Specialists PC, Atlanta, Georgia, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Salzberg
authors.affiliation: Formerly of Janssen Biotech Inc, Horsham, Philadelphia, Pennsylvania, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Diamond
authors.affiliation: Janssen Research & Development, LLC, Edison, New Jersey, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Langholff
authors.affiliation: Janssen Research & Development, LLC, Edison, New Jersey, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Londhe
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
mesh_terms: D000328:Adult; D017677:Age Distribution; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D016001:Confidence Intervals; D003424:Crohn Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D017678:Sex Distribution; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab