The Impact of Timing and Duration of Thiopurine Treatment on First Intestinal Resection in Crohn's Disease: National UK Population-Based Study 1989–2010

Abstract

The efficacy of thiopurines (TPs) in altering the risk of surgery in Crohn's disease (CD) remains controversial. We evaluated the impact of TP therapy, optimal timing, and duration of TP therapy on first intestinal resection rates using a population-based cohort. We constructed a population-based cohort of incident cases of CD between 1989 and 2005. We used the Kaplan-Meier analysis to calculate time trends in TP use and first intestinal resection in three groups defined by time period of diagnosis: 1989-1993, 1994-1999, and 2000-2005 groups A, B, and C, respectively. We quantified impact of duration and timing of TP treatment on likelihood of surgery using Cox regression and propensity score matching. We identified 5,640 eligible patients with CD. The 5-year cumulative probability of TP use increased from 12, 18, to 25% ( P<0.0001) while probability of first intestinal resection decreased from 15, 12 to 9% (P<0.001) in groups A, B, and C, respectively. Patients treated with at least 6 months of TP therapy had a 44% reduction in the risk of surgery (hazards ratio (HR): 0.56; 95% confidence interval (CI): 0.37-0.85) and those receiving at least 12 months of TP therapy had a 69% reduction in the risk of surgery (HR: 0.31; 95% CI: 0.22-0.44). Early treatment (<12 months from diagnosis) vs. late treatment with TP showed no additional benefit in reducing risk of surgery (HR: 0.41; 95% CI: 0.27-0.61 vs. 0.21; 95% CI: 0.13-0.34). Over the past 20 years, TP use has doubled, whereas intestinal surgery has fallen by one-third among the UK population of Crohn's patients. Prolonged exposure is associated with a reduced likelihood of surgery whereby more than 12 months TP therapy reduces the risk of first intestinal surgery two-fold; however, early initiation of TP treatment offered no apparent additional benefit.