title: Crohn's disease outpatients treated with adalimumab have an earlier secondary loss of response and requirement for dose escalation compared to infliximab: a real life cohort study.
abstract: BACKGROUND
  The efficacy of anti-tumor necrosis factor alpha agents in maintaining remission in Crohn's disease may wane over time, leading to secondary loss of response that can often be overcome with dose escalation. Comparison of secondary loss of response of adalimumab and infliximab during long-term treatment of CD in a real-life IBD clinic has not been previously evaluated.
  
  
  METHODS
  A retrospective cohort study was conducted evaluating outpatients with CD on a maintenance regimen with adalimumab or infliximab from 200 to 2013 and who experienced a secondary loss of response. All infliximab-treated patients were anti-TNF naïve. Adalimumab-treated patients were stratified by prior anti-TNF exposure. Kaplan-Meier analysis was conducted to compare time to loss of response.
  
  
  RESULTS
  218 CD patients met inclusion criteria (117 infliximab, 101 adalimumab). Median follow-up duration was 170.0weeks for infliximab and 122.0weeks for adalimumab (p=0.61). The proportion of patients with secondary loss of response was similar for infliximab-treated - 51.3% (60/117) compared to adalimumab patients naïve to anti-TNF therapy - 60.5% (23/38) (p=0.32), and adalimumab patients with prior anti-TNF exposure - 65.1% (41/63) (p=0.08). Median time to secondary loss of response was longer for infliximab patients (99.3wk, IQR 55.7-168.5) compared to both adalimumab patients naïve to anti-TNF therapy (58.9wk, IQR 29.0-85.7) (p=0.03), and adalimumab patients with prior anti-TNF exposure (52.7wk, IQR 20.1-85.0) (p<0.001).
  
  
  CONCLUSIONS
  Over 50% of CD patients treated with infliximab and adalimumab develop secondary loss of response. Time to loss of response was shorter in patients treated with adalimumab compared to those treated with infliximab. Prior anti-TNF exposure further accelerated time to loss of response.
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ma
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Vivian
authors.initials: V
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Darryl K
authors.initials: DK
authors.lastname: Fedorak
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Karen I
authors.initials: KI
authors.lastname: Kroeker
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Dieleman
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Halloran
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: richard.fedorak@ualberta.ca.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000553:Ambulatory Care; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001379:Azathioprine / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D060046:Maintenance Chemotherapy; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D019233:Retreatment; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D001379:Azathioprine; D008727:Methotrexate
keywords: Adalimumab; Crohn's disease; Dose escalation; Infliximab