P428 Optimizing thiopurines in Crohn's disease: low dose and low 6-TGN level are effective for maintenance of remission in Asian population
Mao R.1, Guo J.1, Ben Horin S.1,2, Chen M.*3
1The first affiliated hospital of Sun Yat-Sen University, Department of Radiology, Guangzhou, China 2Sheba Medical Center, Department of Gastroenterology, Tel Hashomer, Israel 3The first affiliated hospital of Sun Yat-Sen University, Department of Gastroenterology, Guangzhou, China
Lower dose of azathioprine (AZA) was suggested in Asian patients with Crohn's disease (CD). However, there was still no recommended dose and 6-TGN level for this population. Our aim was to identify AZA dose and 6-TGN level associated with maintenance of remission in Chinese patients with CD, and to evaluate the putative gain in remission rate by incremental increases in AZA dose and 6-TGN level.
This was a retrospective cohort study of 349 events with CD who used AZA for maintenance of remission CD in a tertiary referral center. The primary endpoint was disease relapse. AZA dose and 6-TGN level were compared in remission group and relapse group. Remission rate was compared across the increased dose range and 6-TGN level.
124 (35.5%) out of 349 events underwent relapse at a median follow-up of 14.2±13.7 months. The AZA dose was higher in remission group compared with that in relapse group (1.63±0.48 mg/kg vs. 1.40±0.53; p=0.000). The association between dose of AZA and rate of remission reached a plateau at 1.5 mg/kg/d, whereas increasing dose of AZA beyond 180 pmol/8×108 RBC produced negligible gain in rate of remission. Frequency of adverse events significantly increased in patients with 6-TGN level >355 pmol/8×108 RBC (8.0% with 6-TGN>355 pmol/8×108 RBC vs. 2.7% with 6-TGN<355 pmol/8×108 RBC, p=0.035).
Lower dose of AZA and lower level of 6-TGN were required for maintenance of remission for Chinese CD patients. We proposed that 6-TGN level of 180–355 pmol/8×108 RBC is adequate for maintenance of remission in 75.3% of Chinese patients with CD, and this could be considered as a “therapeutic window”. Exceeding this level could not produce gain in remission rate but adverse events rate.