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

OBJECTIVES: 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. METHODS: 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. RESULTS: We identifi ed 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 % confi dence 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 benefi t in reducing risk of surgery (HR: 0.41; 95 % CI: 0.27-0.61 vs. 0.21; 95 % CI: 0.13-0.34). CONCLUSIONS: 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 fi rst intestinal surgery two-fold; however, early initiation of TP treatment offered no apparent additional benefit.