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

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.

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.

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.

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.