Hai Yun Shi1, Francis K L Chan2, Wai Keung Leung3, Michael K K Li4, Chi Man Leung5, Shun Fung Sze6, Jessica Y L Ching2, Fu Hang Lo7, Steven W C Tsang8, Edwin H S Shan9, Lai Yee Mak10, Belsy C Y Lam11, Aric J Hui12, Wai Hung Chow13, Marc T L Wong14, Ivan F N Hung3, Yee Tak Hui6, Yiu Kay Chan9, Kam Hon Chan10, Ching Kong Loo11, Carmen K M Ng14, Wai Cheung Lao5, Marcus Harbord15, Justin C Y Wu2, Joseph J Y Sung2, Siew C Ng16. 1. Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China Department of Gastroenterology & Hepatology, Beijing Friendship Hospital, Capital Medical University, Beijing Digestive Disease Center, National Clinical Research Center for Digestive Diseases, China. 2. Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. 3. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. 4. Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong, China. 5. Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. 6. Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China. 7. Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China. 8. Department of Medicine, Tseung Kwan O Hospital, Hong Kong, China. 9. Department of Medicine and Geriatrics, Caritas Medical Center, Hong Kong, China. 10. Department of Medicine, North District Hospital, Hong Kong, China. 11. Department of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong, China. 12. Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China. 13. Department of Medicine, Yan Chai Hospital, Hong Kong, China. 14. Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, China. 15. Department of Gastroenterology, Chelsea and Westminster Hospital, London, UK. 16. Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China.
Abstract
BACKGROUND: Whether low-dose azathioprine (AZA) is effective in maintaining remission in patients with steroid-dependent ulcerative colitis (UC) remains unclear. We assessed the efficacy and safety of low-dose AZA in a Chinese population with UC. METHODS: We identified steroid-dependent UC patients in clinical remission on AZA maintenance therapy from a territory-wide IBD Registry. Standard- and low-dose AZA were defined as at least 2 mg/kg/day and less than 2 mg/kg/day, respectively. Relapse rates were analyzed by Kaplan-Meier analysis and compared using log-rank test. RESULTS: Among 1226 UC patients, 128 (53% male, median duration on AZA 44 months) were included. Median maintenance AZA dose was 1.3 mg/kg/day. 97.7% of the patients were on concomitant oral 5-aminosalicylic acid. Cumulative relapse-free rates in patients on standard-dose and low-dose AZA were 71.2%, 52.8% and 45.2%, and 71.8%, 55.3% and 46.2% at 12, 24 and 36 months, respectively (p = 0.871). Relapse rate within 12 months was higher in patients who withdrew compared with those who maintained on AZA (52.6% versus 29.4%; p = 0.045). Mean corpuscular volume increased after AZA therapy in both of the low-dose [median (interquartile range, IQR): 88.2 (81.4-92.2) versus 95.1 (90.1-100.9) fl, p < 0.001] and standard-dose subgroups [median (IQR) 86.8 (76.9-89.9) versus 94.7 (85.9-99.7) fl, p < 0.001]. Leukopenia occurred in 21.1% of the patients. Patients on standard dose had a higher risk for leukopenia than those on low-dose AZA [odds ratio (OR) 3.9, 95% CI 1.9-8.2, p < 0.001]. CONCLUSIONS: In the Chinese population, low-dose AZA is effective for maintaining remission in steroid-dependent UC patients. Standard-dose AZA was associated with more than threefold increased risk of leukopenia.
BACKGROUND: Whether low-dose azathioprine (AZA) is effective in maintaining remission in patients with steroid-dependent ulcerative colitis (UC) remains unclear. We assessed the efficacy and safety of low-dose AZA in a Chinese population with UC. METHODS: We identified steroid-dependent UC patients in clinical remission on AZA maintenance therapy from a territory-wide IBD Registry. Standard- and low-dose AZA were defined as at least 2 mg/kg/day and less than 2 mg/kg/day, respectively. Relapse rates were analyzed by Kaplan-Meier analysis and compared using log-rank test. RESULTS: Among 1226 UC patients, 128 (53% male, median duration on AZA 44 months) were included. Median maintenance AZA dose was 1.3 mg/kg/day. 97.7% of the patients were on concomitant oral 5-aminosalicylic acid. Cumulative relapse-free rates in patients on standard-dose and low-dose AZA were 71.2%, 52.8% and 45.2%, and 71.8%, 55.3% and 46.2% at 12, 24 and 36 months, respectively (p = 0.871). Relapse rate within 12 months was higher in patients who withdrew compared with those who maintained on AZA (52.6% versus 29.4%; p = 0.045). Mean corpuscular volume increased after AZA therapy in both of the low-dose [median (interquartile range, IQR): 88.2 (81.4-92.2) versus 95.1 (90.1-100.9) fl, p < 0.001] and standard-dose subgroups [median (IQR) 86.8 (76.9-89.9) versus 94.7 (85.9-99.7) fl, p < 0.001]. Leukopenia occurred in 21.1% of the patients. Patients on standard dose had a higher risk for leukopenia than those on low-dose AZA [odds ratio (OR) 3.9, 95% CI 1.9-8.2, p < 0.001]. CONCLUSIONS: In the Chinese population, low-dose AZA is effective for maintaining remission in steroid-dependent UC patients. Standard-dose AZA was associated with more than threefold increased risk of leukopenia.
Authors: P de Graaf; N K H de Boer; D R Wong; S Karner; B Jharap; P M Hooymans; A I Veldkamp; C J J Mulder; A A van Bodegraven; M Schwab Journal: Br J Pharmacol Date: 2010-07 Impact factor: 8.739
Authors: B Jharap; M L Seinen; N K H de Boer; J R van Ginkel; R K Linskens; J C Kneppelhout; C J J Mulder; A A van Bodegraven Journal: Inflamm Bowel Dis Date: 2010-09 Impact factor: 5.325