A controlled double blind study of azathioprine in the management of Crohn's disease.

Abstract

While immunosuppressive agents are used widely in the management of Crohn's disease, their efficacy has not been well established in randomised controlled trials. This study was designed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks. It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn's disease over a period of 15 months. Sixty three patients with active Crohn's disease were treated with a 12 week diminishing dose of prednisolone and at the same time entered into a randomised, double blind 15 month trial of either azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were compared at 12 weeks and at 15 months. There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission (42% receiving azathioprine v 7%/o receiving placebo), p=O0OO1. Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial (p=0.02). There were significandy greater decreases over the trial period in the median erythrocyte sedimentation rate, C reactive protein, and leucocyte count in the azathioprine group. There were no cases of severe bone marrow suppression or clinical pancreatitis. In conclusion, azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn's disease. (Gut 1995; 37: 674-678)

Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine

“…In our series, the probability of remission with corticosteroid withdrawal after 6 and 12 months of remission in patients with active disease at the initiation of the drug was 46% and 79%, respectively, a rate similar to the one reported with AZA/MP. 1,[37][38][39] In patients on TG maintenance therapy, the probability of relapse at 6 and 12 months was 29% and 53%, respectively. The number of patients available for the evaluation of the TG maintenance effect is small (n ¼ 28), and the followup period is still short (median 5 months).…”

Correlation of genotypes for thiopurine methyltransferase and inosine triphosphate pyrophosphatase with long-term clinical outcomes in Korean patients with inflammatory bowel diseases during treatment with thiopurine drugs

“…1,2 There has been tremendous interest with regard to thiopurine metabolism as a means of identifying ways in which individual therapy might maximize clinical response and minimize adverse effects. Genetic polymorphisms in the thiopurine S-methyl transferase (TPMT) gene have been associated with decreased TPMT activity and the development of myelotoxicity due to high thioguanine metabolite concentrations.…”

Steroid Use in Crohn’s Disease

“…It was assessed variously as (i) the ability to follow pre-defined steroid tapering regimen, and (ii) as the ability to reduce steroid dose to < 10 mg/day while maintaining remission. In the five studies reporting data on reduction of steroid consumption patients with active disease who received antimetabolite reduced their steroid consumption more significantly compared to placebo (85)(86)(87)(88)90). In a meta-analysis the pooled OR was 3.69 (95% CI 2.12-6.42) indicating a significant steroid sparing effect (84).…”