Withdrawal of Long-Term Maintenance Treatment with Azathioprine Tends to Increase Relapse Risk in Patients with Crohn’s Disease
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Background and Aim
Many patients with quiescent Crohn’s disease are maintained on long-term treatment with azathioprine (AZA), but controlled data are limited. We aimed to evaluate the efficacy of AZA therapy for more than 4 years to maintain clinical remission.
We performed a randomized double-blind placebo-controlled AZA withdrawal trial with a follow-up period of 24 months. Patients had to have continuous AZA therapy ≥4 years without exacerbation of disease during the 12 months before enrollment, and a Crohn’s disease activity index <150 at baseline. Patients were randomized to continue on AZA or switch to placebo. The primary endpoint was time to clinical relapse during follow-up.
After inclusion of 52 patients, the trial was stopped prematurely due to slow recruitment. During the 2-year follow-up, clinical relapse occurred in 4 of 26 (15 %) patients on continued AZA and in 8 of 26 (31 %) patients on placebo. Time to clinical relapse averaged 22.3 months (95 % CI 20.6–24.0) on AZA and 19.2 months (95 % CI 16.4–22.1) on placebo (p = 0.20). According to life-table analysis, the proportion of patients in remission after 12 and 24 months was 96 ± 4 and 86 ± 7 % in patients receiving AZA versus 76 ± 8 and 68 ± 9 % in patients receiving placebo (month 12, p = 0.035; month 24, p = 0.30). A higher AZA dose at enrollment was an independent predictor for relapse (p < 0.05).
AZA withdrawal resulted in a significantly increased relapse risk after 1 year and a nonstatistically significant trend for relapse after 2 years. Our results are in line with previous observations.
KeywordsCrohn’s disease Immunomodulators Azathioprine Clinical trails
We are thankful to GlaxoSmithKline, Vienna, Austria, for providing the study medication, case report forms, and patient diaries. Representatives of GlaxoSmithKline did not have any role in study design, protocol development, data analysis, data interpretation, writing of the manuscript, or in the decision to submit the manuscript. We thank Marieluise Harrer and Georgiana Prinz for their help in patient recruitment and data acquisition. There was no funding or other financial support for this work.
Conflicts of interest
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