Side effects of azathioprine in patients with Crohn's disease.

OBJECTIVE: In clinical trials 0-15% of patients discontinued azathioprine due to side effects. The aim of this study was to assess the rate of side effects leading to discontinuation of azathioprine and to determine predictive factors for discontinuation.
DESIGN: A retrospective cohort analysis of clinical data regarding adverse events of azathioprine in Crohn's disease. PATIENTS: Azathioprine had been prescribed for 54 of 112 consecutive patients with Crohn's disease. Because incomplete data were available in four patients, the data for 50 patients were analysed.
RESULTS: In 15 of the 50 patients azathioprine was preliminary discontinued due to adverse events and in 11 of these patients (22%) adverse events were probably related to azathioprine. After the onset of therapy, a small, but significant, decrease in leucocyte count was observed within 6 weeks (median from 10.6 to 9.5 x 10(9)/l) and asymptomatic leucopenia (< 3.0 x 10(9)/l) occurred in two patients. Serious adverse events occurred in three patients who, as a result, required admission to hospital. All events were reversible after discontinuation of therapy. Patients who discontinued azathioprine due to adverse events used significantly lower initial doses of prednisone compared to patients who were able to continue azathioprine. The occurrence of side effects was not related to the initial dose of azathioprine or concomitant use of 5-aminosalicylates.
CONCLUSION: Twenty-two per cent of patients discontinued azathioprine prematurely probably as a result of related adverse events. Patients who discontinued azathioprine prematurely used lower doses of prednisone initially. Therefore, concomitant use of prednisone may prevent some of the adverse events.