Toxicity profile of thiopurines in inflammatory bowel disease: a retrospective cohort analysis.

BACKGROUND

Thiopurines have proven efficacy in inflammatory bowel disease. However, their use is limited by adverse effects in a subset of patients.

AIMS: The present study aimed to evaluate toxicity profile and identify clinical predictive factors of thiopurine adverse effects in inflammatory bowel disease patients.

METHODS

A retrospective longitudinal study was conducted among inflammatory bowel disease patients treated with thiopurines. Multiple logistic regression was used to identify risk factors for thiopurine adverse effects.

RESULTS

A total of  210 patients were enrolled in the study. Mean age at disease onset was 29.8±11.4 years.  One hundred sixty-nine (169) patients had Crohn's disease, 29 had ulcerative colitis and 12 had indeterminate colitis. During a median follow-up of 28.5 ± 20 months, 56 patients (26.6%) had thiopurine-related adverse effects including digestive intolerance (n=14; 6.6%), immunoallergic reactions (n=8; 3.8%), myelotoxicity (n=25; 11.9%) and hepatotoxicity (n=8; 3.8%). Treatment withdrawal was reported in 19 patients (9%).  The only independent predictive factor for thiopurine adverse effects found in this study was steroid-dependence (OR= 3.96; 95% CI: 1.07- 14.53; p= 0.038).

CONCLUSIONS

Almost a quarter of inflammatory bowel disease patients treated with thiopurines developed adverse effects. These adverse effects lead to drug withdrawal in almost 9% of patients either as monotherapy or as in combination with biologic therapies.  Steroid-dependent patients were significantly at higher risk for thiopurine-related toxicity.