6-thioguanine--efficacy and safety in chronic active Crohn's disease.
BACKGROUND
: Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side-effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6-thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6-thioguanine in chronic active Crohn's disease.


METHODS
: Thirty-seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6-thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index.


RESULTS
: In the intention-to-treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty-seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 +/- 74 to 153 +/- 101. 6-Thioguanine was more effective in azathioprine-intolerant than in azathioprine-refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6-thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia.


CONCLUSIONS
: In this patient group with chronic active Crohn's disease, 6-thioguanine appeared to be effective with acceptable short-term toxicity, but long-term controlled trials are clearly needed to further define its role.
Herrlinger
K R
KR
Robert-Bosch-Hospital, Stuttgart, Germany. klaus.herrlinger@rbk.de
Kreisel
W
W
Schwab
M
M
Schoelmerich
J
J
Fleig
W E
WE
Ruhl
A
A
Reinshagen
M
M
Deibert
P
P
Fellermann
K
K
Greinwald
R
R
Stange
E F
EF
D000328:Adult; D002908:Chronic Disease; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D015122:Mercaptopurine