Thioguanine: A potential alternate thiopurine for IBD patients allergic to 6-mercaptopurine or azathioprine

被引:87
作者
Dubinsky, MC
Feldman, EJ
Abreu, MT
Targan, SR
Vasiliauskas, EA
机构
[1] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Pediat Inflammatory Bowel Dis Ctr, Div Gastroenterol,Dept Med, Los Angeles, CA 90048 USA
[2] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Div Gastroenterol, Dept Pediat, Los Angeles, CA 90048 USA
关键词
D O I
10.1016/S0002-9270(03)00131-X
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
OBJECTIVE: Approximately 10% of inflammatory bowel disease (IBD) patients receiving 6-mercaptopurine (6-MP) or azathioprine (AZA) develop drug hypersensitivity reactions necessitating early discontinuation of these traditional thiopurines. These allergic reactions typically reoccur upon rechallenge. Our recently published pilot study suggested that thioguanine (6-TG), a closely related thiopurine, was efficacious and well tolerated in IBD patients resistant to 6-MP/AZA. The aim of this study was to determine if hypersensitivity reactions to 6-MP/AZA reoccur with 6-TG therapy. METHODS: IBD patients allergic to 6-MP and/or AZA were treated with 6-TG as an alternate thiopurine. Hypersensitivity reactions to 6-MP/AZA must have been documented within 6 wk of 6-MP/AZA initiation. RESULTS: 6-TG was initiated in 21 IBD patients at a median (range) dose of 20 (10-40) mg/day. 6-TG hypersensitivity reaction occurred in only four of 21 (19%) patients after a median time interval of 9 days. Pancreatitis did not reoccur with 6-TG. Eighty-two percent of 6-TG tolerant patients were assessed as improved at last follow-up. CONCLUSIONS: These results suggest that 6-TG may be considered as a possible alternate thiopurine in patients allergic to traditional 6-MP/AZA. Despite these favorable results, candidates for 6-TG should be selected with caution, and its use should be reserved for IBD patients well informed about potential toxicities. (C) 2003 by Am. Coll. of Gastroenterology.
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页码:1058 / 1063
页数:6
相关论文
共 44 条
[1]   Portal hypertension in the presence of minimal liver damage in Crohn's disease on long-term azathioprine: possible endothelial cell injury [J].
Arnott, IDR ;
Ghosh, S .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2000, 12 (05) :569-573
[2]   RAPID DEVELOPMENT OF PANCREATITIS FOLLOWING REUSE OF 6-MERCAPTOPURINE [J].
CAPPELL, MS ;
DAS, KM .
JOURNAL OF CLINICAL GASTROENTEROLOGY, 1989, 11 (06) :679-681
[3]   HYPERSENSITIVITY AND JAUNDICE DUE TO AZATHIOPRINE [J].
DAVIS, M ;
WILLIAMS, R ;
EDDLESTON, ALWF .
POSTGRADUATE MEDICAL JOURNAL, 1980, 56 (654) :274-275
[4]   Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease [J].
Dubinsky, MC ;
Lamothe, S ;
Yang, HY ;
Targan, SR ;
Sinnett, D ;
Théorêt, Y ;
Seidman, EG .
GASTROENTEROLOGY, 2000, 118 (04) :705-713
[5]   An open-label pilot study using thioguanine as a therapeutic alternative in Crohn's disease patients resistant to 6-mercaptopurine therapy [J].
Dubinsky, MC ;
Hassard, PV ;
Seidman, EG ;
Kam, LY ;
Abreu, MT ;
Targan, SR ;
Vasiliauskas, EA .
INFLAMMATORY BOWEL DISEASES, 2001, 7 (03) :181-189
[6]  
DUBINSKY MC, 2000, GASTROENTEROLOGY, V118, pA492
[7]  
DUVOUX C, 1991, GASTROEN CLIN BIOL, V15, P968
[8]   Pharmacokinetics and metabolism of thiopurines in children with acute lymphoblastic leukemia receiving 6-thioguanine versus 6-mercaptopurine [J].
Erb, N ;
Harms, DO ;
Janka-Schaub, G .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1998, 42 (04) :266-272
[9]  
FRANCOIS L, 1997, DIS DIS SCI, V42, P823
[10]   NODULAR REGENERATIVE HYPERPLASIA OF THE LIVER GRAFT AFTER LIVER-TRANSPLANTATION [J].
GANE, E ;
PORTMANN, B ;
SAXENA, R ;
WONG, P ;
RAMAGE, J ;
WILLIAMS, R .
HEPATOLOGY, 1994, 20 (01) :88-94