On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprine or 6-mercaptopurine intolerant IBD patients.
OBJECTIVE
To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.


METHODS
Database analysis.


RESULTS
Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8 x 10(8) RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%) and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.


CONCLUSIONS
The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.
de Boer
Nanne-K-H
NK
Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands.
Derijks
Luc-J-J
LJ
Gilissen
Lennard-P-L
LP
Hommes
Daniel-W
DW
Engels
Leopold-G-J-B
LG
de-Boer
Sybrand-Y
SY
den Hartog
Gijsbertus
G
Hooymans
Piet-M
PM
Mäkelburg
Anja-B-U
AB
Westerveld
Barend-D
BD
Naber
Anton-H-J
AH
Mulder
Chris-J-J
CJ
de Jong
Dirk-J
DJ
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects; D008875:Middle Aged; D012189:Retrospective Studies; D012449:Safety; D013866:Thioguanine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine