An open study reported that patients with Crohn's disease in remission who have taken azathioprine for longer than 4 years are at low risk of relapse when azathioprine is discontinued.
To confirm this observation, Dr Lémann and colleagues from France performed a multicenter, double-blind, noninferiority withdrawal study.
|At 18 months, 3 patients had a relapse in the azathioprine group, versus 9 in the placebo group|
The research team included patients who were in clinical remission on azathioprine for more than 42 months.
The researchers randomized patients to continue azathioprine or to receive an equivalent placebo for 18 months.
The primary end point was clinical relapse at 18 months.
The team randomly assigned 40 patients to receive azathioprine and 43 to receive placebo.
The researchers reported that the characteristics of patients at entry were similar in the 2 study groups.
The team found that at 18 months, 3 patients had a relapse in the azathioprine group, and 9 had a relapse in the placebo group.
The researchers used Kaplan-Meier estimates to show that the relapse rate at 18 months were 8% and 21%, respectively.
The team's hypothesis that placebo was inferior to azathioprine was not rejected.
The team identified predictive markers among the baseline variables for relapse that included C-reactive protein levels more than 20 mg/L.
The team also found that time without steroids less than 50 months, and hemoglobin level less than 12 g/dL were predictive of relapse with multivariate analysis.
Dr Lémann's team concludes, “This study shows that azathioprine withdrawal is not equivalent to continued therapy with azathioprine for maintenance of remission in patients with Crohn's disease who have been in remission on azathioprine for more than 4 years.”
“Thus, azathioprine maintenance therapy should be continued beyond 4 years.”