Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year intercept cohorts.
BACKGROUND
Thiopurines have proven efficacy in long-term maintenance therapy of inflammatory bowel disease (IBD). Limited data are available with regard to factors predicting effectiveness and failure of long-term thiopurine use in IBD patients.


METHODS
The data in this retrospective study are based on an 8-year intercept cohort of previous or present thiopurine-using IBD patients. Both cohorts are assessed by descriptive and statistical analysis aimed at determining thiopurine effectiveness and the variables that are predictive for failure of thiopurine therapy.


RESULTS
In all, 363 IBD patients were included (60% female), 63% with Crohn's disease and 33% with ulcerative colitis. Overall, thiopurines were continued in 145/363 (40%) and discontinued in 208/363 (57%) patients. The proportion of patients still using thiopurines at 3, 6, 12, 24, and 60 months was 73%, 69%, 63%, 51%, and 42%, respectively. Patients discontinued thiopurines due to adverse events (39%), refractoriness (16%), and ongoing remission / patient's request (4%). 6-methylmercaptopurine (6-MMP) concentration and 6-MMP/6-thioguanine nucleotides (6-TGN) ratio were significant higher in the failure group. Prolonged continuation of thiopurines was associated with a decreased risk of discontinuation.


CONCLUSIONS
Azathioprine and 6-mercaptopurine were considered effective in approximately 40% of IBD patients after 5 years of treatment. A quarter of the patients discontinued thiopurines within 3 months, mostly due to adverse events. A high 6-MMP concentration or 6-MMP/6-TGN ratio was associated with therapeutic failure. If thiopurine use was successfully initiated in the first months, its use was usually extended over many years, as long-term use was associated with continuation of therapy.
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands. b.jharap@vumc.nl
B
B
Jharap
M L
ML
Seinen
N K H
NK
de Boer
J R
JR
van Ginkel
R K
RK
Linskens
J C
JC
Kneppelhout
C J J
CJ
Mulder
A A
AA
van Bodegraven
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D001379:Azathioprine