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Thiopurines have been considered the reference treatment for patients with steroid-dependent moderate to severe IBD for many years. This has been based on evidence describing the efficacy and safety of azathioprine and mercaptopurine in Crohn's disease (CD) and UC. In CD, efficacy has been established through controlled trials, meta-analyses, cohort studies and data on mucosal healing, as well as in withdrawal studies. A Cochrane meta-analysis concluded that azathioprine and mercaptopurine effectively maintained remission in CD with an OR between 2 and 3 compared to placebo.1 Mucosal healing was initially studied in patients on azathioprine with longstanding steroid-free remission.2 In this setting, full mucosal healing was achieved in 54% of patients with ileitis and 70% with colitis. The majority of the remaining patients had at least partial healing, and only a small minority experienced no healing at all. This healing potential was confirmed in a controlled study showing the superiority of azathioprine over budesonide.3 When patients achieve sustained steroid-free remission under azathioprine, it is usually stable and longstanding. A controlled withdrawal study from the GETAID indicated sustained remission over more than 5 years in 80% of patients when the treatment was continued, compared to 40% of patients when it was stopped.4
The evidence base in UC is weaker. Nevertheless, a controlled trial comparing azathioprine to mesalazine in steroid-dependent UC clearly showed the superiority of azathioprine with an OR of 4.8 (95% CI 1.6 to 14.5).5 This benefit was confirmed in a meta-analysis.6 Additionally, a withdrawal study, although not controlled, showed around 60% of patients with UC relapse over 5 years after azathioprine withdrawal.7
In CD, these data have also been reinforced by cohort studies suggesting a beneficial effect of thiopurines on long-term outcome, including a decrease in the rate of surgery in adult and paediatric patients. …
Contributors EL, PI and LB have all actively contributed in the writing of this manuscript and and reviewed and agreed on the final manuscript.
Competing interests EL has received fees for: research grant: AstraZeneca, Schering-Plough, Abbott. Speaker fees: Abbott, Abbvie, AstraZeneca, Ferring, Schering-Plough, MSD, Chiesi, Menarini, Nycomed, Falk, UCB. Advisory board: Abbott, Abbvie, Ferring, UCB, MSD, Millenium, Mitsubishi Pharma, Takeda. Consultant: Abbvie.
Provenance and peer review Commissioned; externally peer reviewed.
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