title: Long-term results with azathioprine therapy in patients with corticosteroid-dependent Crohn's disease: open-label prospective study.
abstract: BACKGROUND
  A substantial number of patients with Crohn's disease (CD) become dependent on steroids after induction therapy. Treatment with azathioprine (AZA) may be beneficial in such patients. The present open-label study evaluated the long-term safety and efficacy of AZA in steroid-dependent CD patients.
  
  
  METHODS
  Adult patients with steroid-dependent CD were enrolled for AZA therapy over a 7-year period. The average dose of AZA was 2.0-3.0 mg/kg per day, adjusted according to clinical response and occurrence of adverse effects. Steroid therapy was tapered off according to a predefined schedule. Long-term outcome and adverse reactions were evaluated.
  
  
  RESULTS
  Sixty-nine patients were prospectively included. Steroid-free remission was achieved in 68-81% of patients, partial response in 14.5-27.3% and failure to respond to AZA in 4-15.9% over the initial 48 months. However, the rate of wean from steroid therapy decreased to 53-60% while the rate of failure increased from 6.7% to 17.6% after this period. A breakthrough of symptoms during continuous AZA therapy was common, particularly after 48 months on AZA. The mean leukocyte count at the end of 12 months of therapy was significantly lower in patients who achieved complete response on AZA than in the non-responders (5197 +/- 1250 cells/mm(3) vs 8340 +/- 1310 cells/mm(3), respectively; P < 0.01). Azathioprine was relatively well-tolerated and the incidence of serious adverse effects was small.
  
  
  CONCLUSIONS
  Azathioprine was relatively safe and moderately effective for long-term maintenance of steroid-free clinical remission in corticosteroid-dependent CD patients. Patients were more successfully weaned from prednisone treatment, and clinical remission was more often maintained during the first 48 months of AZA therapy. A significant decrease in the white blood cell count at the end of 12 months on AZA was the single factor associated with weaning from steroid dependence.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Diseases Center, University Hospital of the Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil. chebli@globo.com
authors.forename: Julio Maria Fonseca
authors.initials: JM
authors.lastname: Chebli
authors.forename: Pedro Duarte
authors.initials: PD
authors.lastname: Gaburri
authors.forename: Aécio Flávio Meirelles
authors.initials: AF
authors.lastname: De Souza
authors.forename: André Luiz Tavares
authors.initials: AL
authors.lastname: Pinto
authors.forename: Liliana Andrade
authors.initials: LA
authors.lastname: Chebli
authors.forename: Guilherme Eduardo Gonçalves
authors.initials: GE
authors.lastname: Felga
authors.forename: Cecília Ganini
authors.initials: CG
authors.lastname: Forn
authors.forename: Carolina Frade Magalhães Girardin
authors.initials: CF
authors.lastname: Pimentel
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D001379:Azathioprine