title: Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease.
abstract: OBJECTIVE
  A small placebo-controlled trial reported the efficacy of mercaptopurine therapy for children newly diagnosed with Crohn's disease, yet little is known about the efficacy of early thiopurine therapy in adults.
  
  
  METHODS
  We performed a prospective double-blind trial of adult patients with a recent (<8 weeks) diagnosis of Crohn's disease. Patients were randomly assigned to groups given azathioprine (2.5 mg · kg(-1) · day(-1), n = 68) or placebo (n = 63) at 31 hospitals from February 2006 to September 2009. Corticosteroids but no other concomitant medications were allowed for control of disease activity. The primary measure of efficacy was sustained corticosteroid-free remission.
  
  
  RESULTS
  After 76 weeks of treatment, 30 patients treated with azathioprine (44.1%) and 23 given placebo (36.5%) were in sustained corticosteroid-free remission (difference of 7.6%; 95% confidence interval, -9.2 to 24.4%; P = .48). The rates of relapse (defined as Crohn's Disease Activity Index score >175) and corticosteroid requirements were similar between groups. A post hoc analysis of relapse, defined as a Crohn's Disease Activity Index score >220, showed lower relapse rates in the azathioprine group than in the placebo group (11.8% vs 30.2%; P = .01). Serious adverse events occurred in 14 patients in the azathioprine group (20.6%) and 7 in the placebo group (11.1%) (P = .16). A larger percentage of patients in the azathioprine group had adverse events that led to study drug discontinuation (20.6%) than in the placebo group (6.35%) (P = .02).
  
  
  CONCLUSIONS
  In a study of adults with Crohn's disease, early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis. EudraCT 2005-001186-34.
authors.affiliation: Hospital Clínic/IDIBAPS, Barcelona, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. Electronic address: jpanes@clinic.cat.
authors.forename: Julián
authors.initials: J
authors.lastname: Panés
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Sanromán
authors.forename: Fernando
authors.initials: F
authors.lastname: Bermejo
authors.forename: Valle
authors.initials: V
authors.lastname: García-Sánchez
authors.forename: Maria
authors.initials: M
authors.lastname: Esteve
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Torres
authors.forename: Eugeni
authors.initials: E
authors.lastname: Domènech
authors.forename: Marta
authors.initials: M
authors.lastname: Piqueras
authors.forename: María
authors.initials: M
authors.lastname: Gomez-García
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: Carlos
authors.initials: C
authors.lastname: Taxonera
authors.forename: Miquel
authors.initials: M
authors.lastname: Sans
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: AZTEC Study; C-reactive protein; CD; CDAI; CI; CRP; Corticosteroids; Crohn's Disease Activity Index; Crohn's disease; IBDQ; Inflammatory Bowel Disease Questionnaire; Inflammatory Bowel Diseases; RR; Treatment; confidence interval; relative risk