Prolonged azathioprine treatment reduces the need for surgery in early Crohn's disease

J Gastroenterol Hepatol. 2018 Mar;33(3):664-670. doi: 10.1111/jgh.14000.

Abstract

Background and aim: Whether an early use of azathioprine (AZA) can alter the natural history of Crohn's disease (CD) remains debated. The aim of this study is to evaluate the impact of AZA on disease progression in a cohort of patients with early CD.

Methods: This longitudinal cohort study examined patients with early CD defined as disease duration ≤ 18 months and no previous use of disease-modifying agents according to Paris definition. The primary outcome was the proportion of CD-related intestinal surgery. Cox regression analysis was performed to identify potential predictive factors of CD progression.

Results: One-hundred and ninety patients with early CD were enrolled in the study. After a median follow-up of 57 months (interquartile range, 31.3-76.2), 31 patients underwent abdominal surgeries, 48 patients were hospitalized, and 68 patients experienced clinical flares. The cumulative rate of remaining free of CD-related bowel surgery, hospitalization, and flare at 5 years on AZA treatment was 0.65, 0.59, and 0.39, respectively. Three independent predictors of CD-related operations were identified: prior bowel resection (hazard ratio [HR], 9.23; 95% confidence interval [CI] 3.67-23.23), smoker (HR, 4.0; 95% CI 1.38-11.65), and hemoglobin < 110 g/L at the time of initiation of AZA (HR, 4.36; 95% CI 1.80-10.58). Conversely, AZA treatment duration > 36 months (HR, 0.04; 95% CI 0.01-0.15) was associated with reduced CD-related operations.

Conclusion: Prior bowel resection, smoking, and hemoglobin < 110 g/L at the time of initiation of AZA were risk factors associated with intestinal surgery in patients with early CD. However, prolonged use (≥ 36 months) of AZA was associated with a more favorable disease course of early CD.

Keywords: early CD; intestinal surgery; thiopurine.

MeSH terms

  • Adult
  • Azathioprine / administration & dosage*
  • Cohort Studies
  • Crohn Disease / drug therapy*
  • Crohn Disease / surgery*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Hemoglobins / metabolism
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Longitudinal Studies
  • Male
  • Proportional Hazards Models
  • Risk Factors
  • Smoking / adverse effects
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Hemoglobins
  • Immunosuppressive Agents
  • Azathioprine