Adverse Events Associated with Azathioprine Treatment in Korean Pediatric Inflammatory Bowel Disease Patients
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Purpose: This study was aimed to evaluate the frequency and course of adverse events associated with azathioprine treatment in Korean pediatric patients with inflammatory bowel disease. Methods: Total of 174 pediatric patients (age range, 1 to 19 years) with inflammatory bowel disease who received azathioprine in order to maintain remission at Samsung Medical Center (Seoul, Korea) from January 2002 through December 2012 were included in this study. Medical records of these subjects were retrospectively reviewed regard-ing the development of adverse events associated with azathioprine treatment.Results: Ninety-eight patients (56.3%) of 174 patients experienced 136 episodes of adverse events, requiring dose reduction in 31 patients (17.8%), and discontinuation in 18 patients (10.3%). The mean dose of azathioprine that had been initially administered was 1.32±0.42 mg/kg/day. Among the adverse reactions, bone marrow suppression developed in 47 patients (27.0%), requiring dose reduction in 22 patients (12.6%) and discontinuation in 8 patients (4.6%). Other adverse events that occurred were gastrointestinal disturbance (15.5%), hair loss (12.1%), pancreatitis (7.5%), arthralgia (6.9%), hepatotoxicity (2.9%), skin rash/allergic reactions (2.9%), headache/dizziness (2.3%), sepsis (0.6%), and oral mucositis (0.6%). Conclusion: Bone marrow suppression, especially leukopenia was most commonly associated with azathioprine treatment in Korean pediatric inflammatory bowel disease patients. Close observation for possible adverse events is required in this population with inflammatory bowel diseases who are under treatment with azathioprine. (Pediatr Gastroenterol Hepatol Nutr 2013; 16: 171∼177)
Abstract
Purpose: This study was aimed to evaluate the frequency and course of adverse events associated with azathioprine treatment in Korean pediatric patients with inflammatory bowel disease. Methods: Total of 174 pediatric patients (age range, 1 to 19 years) with inflammatory bowel disease who received azathioprine in order to maintain remission at Samsung Medical Center (Seoul, Korea) from January 2002 through December 2012 were included in this study. Medical records of these subjects were retrospectively reviewed regard-ing the development of adverse events associated with azathioprine treatment.Results: Ninety-eight patients (56.3%) of 174 patients experienced 136 episodes of adverse events, requiring dose reduction in 31 patients (17.8%), and discontinuation in 18 patients (10.3%). The mean dose of azathioprine that had been initially administered was 1.32±0.42 mg/kg/day. Among the adverse reactions, bone marrow suppression developed in 47 patients (27.0%), requiring dose reduction in 22 patients (12.6%) and discontinuation in 8 patients (4.6%). Other adverse events that occurred were gastrointestinal disturbance (15.5%), hair loss (12.1%), pancreatitis (7.5%), arthralgia (6.9%), hepatotoxicity (2.9%), skin rash/allergic reactions (2.9%), headache/dizziness (2.3%), sepsis (0.6%), and oral mucositis (0.6%). Conclusion: Bone marrow suppression, especially leukopenia was most commonly associated with azathioprine treatment in Korean pediatric inflammatory bowel disease patients. Close observation for possible adverse events is required in this population with inflammatory bowel diseases who are under treatment with azathioprine. (Pediatr Gastroenterol Hepatol Nutr 2013; 16: 171∼177)
참고문헌 (19)
- Chande N, "Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease", Cochrane Database Syst Rev, 4 (2013)
- Derijks LJ, "Review article: thiopurines in inflammatory bowel disease", Aliment Pharmacol Ther, 24, pp.715~729 (2006)
- Gisbert JP, "Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: a review", Am J Gastroenterol, 103, pp.1783~1800 (2008)
- Winter JW, "Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease", Aliment Pharmacol Ther, pp.1069~1077 (2007)
- Ansari A, "Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease", Aliment Pharmacol Ther, 28, pp.973~983 (2008)
- Gearry RB, "Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease", Pharmacoepidemiol Drug Saf, 13, pp.563~567 (2004)
- Gisbert JP, "Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine in inflammatory bowel disease: long-term follow-up study of 394 patients", Am J Gastroenterol, 101, pp.2769~2776 (2006)
- 김재학, "염증성 장질환 환자에서 Azathioprine", 6-Mercaptopurine 치료의 부작용: 빈도와 경과, 2008, pp.51(5), 291~297[DOI]
- Kirschner BS, "Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease", Gastroenterology, 115, pp.813~821 (1998)
- Kader HA, "Normal thiopurine methyltransferase levels do not eliminate 6-mercaptopurine or azathioprine toxicity in children with inflammatory bowel disease", J Clin Gastroenterol, 30, pp.409~413 (2000)
- Tajiri H, "Efficacy and safety of azathioprine and 6-mercaptopurine in Japanese pediatric patients with ulcerative colitis: a survey of the Japanese Society for Pediatric Inflammatory Bowel Disease", Digestion, 77, pp.150~154 (2008)
- Chouchana L, "Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease", Aliment Pharmacol Ther, 35, pp.15~36 (2012)
- Lennard L, "Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism", Clin Pharmacol Ther, 46, pp.149~154 (1989)
- Cao Q, "Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease", Digestion, 79, pp.58~63 (2009)
- Otterness D, "Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms", Clin Pharmacol Ther, 62, pp.60~73 (1997)
- Collie-Duguid ES, "The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations", Pharmacogenetics, 9, pp.37~42 (1999)
- Colombel JF, "Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy", Gastroenterology, 118, pp.1025~1030 (2000)
- Oevermann L, "Hematopoietic stem cell differentiation affects expression and function of MRP4 (ABCC4), a transport protein for signaling molecules and drugs", Int J Cancer, 124, pp.2303~2311 (2009)
- Krishnamurthy P, "Transporter-mediated protection against thiopurine-induced hematopoietic toxicity", Cancer Res, 68, pp.4983~4989 (2008)
