title: Azathioprine discontinuation earlier than 6 months in Crohn's disease patients started on anti-TNF therapy is associated with loss of response and the need for anti-TNF dose escalation.
abstract: OBJECTIVE
  A high proportion of Crohn's disease (CD) patients lose response to antitumor necrosis factor (anti-TNF) and therapy needs to be intensified. We aimed to prospectively determine the predictors and frequency of anti-TNF loss of response and therefore the need for dose escalation and de-escalation in CD patients treated with infliximab or adalimumab.
  
  
  METHODS
  All patients were anti-TNF naive while concomitant azathioprine was administered for 6 months. In patients initially responding to anti-TNF and subsequently losing clinical response after the first 14 weeks of therapy, dose escalation was scheduled. During the follow-up period and after 1 year of intensified administration, anti-TNF was de-escalated in patients in remission.
  
  
  RESULTS
  A total of 161 patients were started on infliximab (n=96) or adalimumab (n=65); however, 29 patients (18.0%) did not respond to therapy and were excluded from further analysis. From the remaining 132 patients (infliximab=77, adalimumab=55), 31 (23.5%) needed a dose escalation for maintenance of remission during a median 28-month follow-up period. Factors associated with loss of response and therefore the need for anti-TNF dose escalation were azathioprine discontinuation earlier than 6 months and smoking. Most patients achieved clinical remission (n=25, 80.6%) without other interventions and among these, 16 patients (64%) were successfully de-escalated to the standard maintenance infliximab or adalimumab dose schedule after 1 year of intensified anti-TNF administration.
  
  
  CONCLUSIONS
  Azathioprine discontinuation earlier than 6 months and smoking in CD patients started on anti-TNF therapy is associated with loss of response and the need for anti-TNF dose escalation.
authors: aDepartment of Gastroenterology, Evangelismos Hospital, Athens bDepartment of Gastroenterology, University Hospital of Patras, Rio, Greece.
authors: Nikos
authors: N
authors: Viazis
authors: Theodoros
authors: T
authors: Koukouratos
authors: Jiannis
authors: J
authors: Anastasiou
authors: Marios
authors: M
authors: Giakoumis
authors: Christos
authors: C
authors: Triantos
authors: Chrisostomos
authors: C
authors: Tsolias
authors: Georgios
authors: G
authors: Theocharis
authors: Dimitrios G
authors: DG
authors: Karamanolis
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001379:Azathioprine / Q000008:administration & dosage* / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D060828:Induction Chemotherapy / Q000379:methods; D000069285:Infliximab / Q000008:administration & dosage* / Q000627:therapeutic use; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D000069285:Infliximab; D000068879:Adalimumab; D001379:Azathioprine