6-tioguanine monitoring in steroid-dependent patients with inflammatory bowel diseases receiving azathioprine.
BACKGROUND
6-Thioguanine (6-tioguanine) nucleotides are the active metabolites of azathioprine.


OBJECTIVE
The aim of the study was to evaluate the rate of clinical remission without steroids in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium- and long-term efficacy and the predictive factors of clinical response when monitoring 6-tioguanine.


METHODS
Steroid-dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6-tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients.


RESULTS
A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention-to-treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6-tioguanine >250 pmol/8 x 10(8) RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6-tioguanine level >250 pmol/8 x 10(8) RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells was a predictive factor of favourable clinical remission.


CONCLUSIONS
Clinical remission without steroids is significantly more likely when monitoring 6-tioguanine so as to reach a level of >250 pmol/8 x 10(8) red blood cells in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).
Roblin
X
X
Département d'Hépato-Gastroentérologie, CHU de Grenoble, 38043 Grenoble Cedex, France.
Serre-Debeauvais
F
F
Phelip
J-M
JM
Faucheron
J-L
JL
Hardy
G
G
Chartier
A
A
Helluwaert
F
F
Bessard
G
G
Bonaz
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine