Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine.
BACKGROUND
Tioguanine (TG) is an antimetabolite which may be regarded as an alternative to azathioprine (AZA)/mercaptopurine (MP) in patients with inflammatory bowel diseases.


OBJECTIVE
: To evaluate the tolerance and efficacy of TG in patients with Crohn's disease, intolerant or resistant to AZA/MP.


METHODS
An open prospective study was made on Crohn's disease patients treated with TG. Intolerance to AZA/MP was defined as a reaction occurring within 1 month after introduction of AZA/MP, including pancreatitis, abdominal pain, fever, arthralgia, myalgia, cutaneous rash, fatigue, alopecia, hepatitis and digestive intolerance. Resistance to AZA/MP was defined as the persistence of activity after at least 3 months of AZA/MP therapy.


RESULTS
Forty-nine Crohn's disease patients (36 women, 13 men; intolerance: n = 39; resistance: n= 10) were treated with TG (20 mg/day). Clinical pancreatitis did not recur under TG. Five patients (10%) had to stop TG due to intolerant reactions observed 13-21 days after TG was started. No haematological side-effects were observed under TG. The probability of clinical remission without corticosteroids or infliximab at 6 and 12 months was 46% and 79%, respectively, in the 40 patients with active disease at baseline. The probability of clinical relapse during maintenance TG therapy at 6 and 12 months was 29% and 53%, respectively, in the 28 patients in remission at baseline or who had achieved remission on TG.


CONCLUSIONS
TG is a possible alternative treatment in Crohn's disease patients, intolerant (especially for pancreatitis) or resistant to AZA/MP.
Bonaz
B
B
Département d'Hépato-Gastroentérologie, CHU de Grenoble, France. Bruno.Bonaz@uif-grenoble.fr
Boitard
J
J
Marteau
P
P
Lémann
M
M
Coffin
B
B
Flourié
B
B
Belaiche
J
J
Cadiot
G
G
Metman
E-H
EH
Cortot
A
A
Colombel
J-F
JF
D000328:Adult; D000963:Antimetabolites / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D013866:Thioguanine / Q000627:therapeutic use*; D016896:Treatment Outcome
D000963:Antimetabolites; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine