Tioguanine in the treatment of refractory coeliac disease--a single centre experience.
BACKGROUND
Refractory coeliac disease type I is a complicated form of coeliac disease characterised by primary or secondary resistance to a gluten-free diet with persisting or reoccurring intestinal villous atrophy and symptoms of malabsorption. Besides corticosteroids, azathioprine has been advocated for the treatment of refractory coeliac disease type I. However, tioguanine (TG) might be better tolerated and more efficacious owing to a simpler metabolism towards bioactivation.


OBJECTIVE
To evaluate tolerability and effectiveness of the nonconventional thiopurine derivative TG in refractory coeliac disease type I.


METHODS
Refractory coeliac disease type I patients treated with TG between June 2001 and November 2010 with a follow-up period of at least 1 year were included. Adverse events, laboratory values, 6-thioguanine nucleotide concentrations and rates of both clinical and histological response were evaluated at baseline and during follow-up.


RESULTS
Twelve adult refractory coeliac disease type I patients were included. The median TG treatment duration was 14 months. Ten patients tolerated TG treatment on the long term, whereas two patients withdrew treatment due to adverse events. No nodular regenerative hyperplasia of the liver was observed. During follow-up clinical and histological response was observed in 83% and 78%, respectively. Corticosteroid dependency decreased by 50%.


CONCLUSIONS
Tioguanine appears to be a convenient drug for the treatment of refractory coeliac disease type I based on higher histological and similar clinical response rates as compared with historical conventional therapies.
Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands. g.tack@vumc.nl
G J
GJ
Tack
D P
DP
van Asseldonk
R L J
RL
van Wanrooij
A A
AA
van Bodegraven
C J
CJ
Mulder
D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002446:Celiac Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006150:Guanine Nucleotides / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013866:Thioguanine / Q000009:adverse effects / Q000627:therapeutic use*; D013873:Thionucleotides / Q000097:blood* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D013866:Thioguanine