Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year intercept cohorts

Abstract

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.