S1100 When Can We Stop Azathioprine in Crohn's Disease Patients in Long-Term Remission?

Abstract

Introduction: Azathioprine (AZA) is an efficient maintenance treatment in Crohn's disease (CD). Most of the risks of AZA use rely on prolonged exposure duration and withdrawal when possible is a therapeutic option. A randomised control trial of the GETAID showed that AZA withdrawal in patients with CD who have been in remission for >3.5 years increased the relapse rate compared to those who continued the treatment. The aim of our study was to assess whether longer use of AZA allows to decrease the relapse rate in CD. Patients and methods: Among the 4035 patients with CD evaluated in our tertiary center, medical files from 47 patients who stopped AZA for personal convenience during remission and after a minimum of 3.5 years of treatment were retrospectively analyzed. Clinical and follow up data were compared to those of a control group composed of CD patients matched 2 on 1 for AZA initiation date and who continued with AZA beyond the withdrawal date of the case (94 patients). In the second part of the study, the AZAwithdrawal group was dichotomised on the median treatment duration of this group (72 months), to compare relapse rate between early and late withdrawal. Statistical analysis evaluated the relapse free survival rate (KaplanMeier method) after AZA withdrawal. Survival curves were compared using log rank test and factors associated with relapse were obtained using Cox model. Results: Both patients groups were similar regarding gender, age at AZA initiation, relapsed time between CD diagnosis and AZA initiation, CD phenotype and location (according to Montreal classification) and smoking habits. Patients from the AZA withdrawal group had an increased relapse rate compared to the controls (57.3% vs 17.6% at 2 years and 73.3% vs 44.4% at 5 years, respectively; p=0.0009). In the AZA withdrawal group, late withdrawal (after: 98.4 ± 5.7 months; [72.0-164.0]) led to a similar relapse rate than early withdrawal (after: 58.7 ± 1.6 months; [41.0-69.7]) with relapse rates of 61% vs 54% at 2 years and 68% vs 78% at 5 years (p=0.89), respectively. In the AZA withdrawal group, factors independently associated with relapse were: male gender (OR=2.42; [1.66-3.52]; p=0.019) and absence of smoking (OR=2.78; [0.25-0.52]; p=0.006). Conclusion: AZA withdrawal exposes to a high relapse rate regardless of the treatment duration, even when it is above 6 years. Non smoking male patients seem to be more exposed to relapse. These data are in favour of an extended AZA maintenance therapy, and particularly in non smoking male. In case of AZA withdrawal, substitution with another maintenance treatment seems required.