Predictors of Thiopurine Treatment Failure in Biologic-Naïve Ulcerative Colitis Patients

Document Type


Publication Date


Publication Title

Digestive diseases and sciences


INTRODUCTION: Thiopurines (azathioprine and 6-mercaptopurine) have been used in the management of UC patients for over three decades. Nearly half of patients with UC treated with thiopurines fail to achieve remission or lose remission during treatment. Factors associated with thiopurine failure are poorly understood. The primary aim of our study was to investigate patient-related factors which are associated with thiopurine failure.

METHODS: TNF-alpha antagonist-naïve patients with histological diagnosis of UC, receiving thiopurine therapy, with follow-up data from 1 to 3 years were included in the study. Data regarding demographics, laboratory results, and disease characteristics were collected. The primary endpoint was failure of thiopurine therapy, defined as treatment with steroids, therapeutic escalation to TNF-alpha antagonist therapy, or need for surgery.

RESULTS: Of the 563 patients identified using ICD-9 codes, 78 TNF-alpha antagonist-naïve patients with a histological diagnosis of UC, receiving thiopurine treatment, were identified. Over the three-year follow-up period, 38 patients failed thiopurine treatment. On adjusted Cox regression, BMI < 25 kg/m(2) (HR 3, 95 % CI 1.55-5.83; p value = 0.001) was significantly associated with thiopurine failure. Furthermore, although not statistically significant, there was a strong trend toward thiopurine failure among patients with serum albumin level < 4 g/dL (HR 1.98, 95 % CI 0.97-4; p value = 0.06), non-smoking status (HR 2.2, 95 % CI 0.96-5.06; p value = 0.06), and higher degree of colon inflammation (HR 1.49, 95 % CI 0.96-2.32; p value = 0.08).

DISCUSSION: Our results show that low body mass index is associated with increased risk of failure of thiopurine treatment. Furthermore, there was a strong trend toward thiopurine failure among patients with low serum albumin level (<4gm/dL). These factors should be considered as markers of non-response to thiopurine monotherapy for patients with moderately severe ulcerative colitis.

Medical Subject Headings

Adult; Anti-Inflammatory Agents; Azathioprine; Biological Products; Biomarkers; Body Mass Index; Chi-Square Distribution; Colitis, Ulcerative; Digestive System Surgical Procedures; Drug Substitution; Female; Gastrointestinal Agents; Humans; Hypoalbuminemia; Male; Mercaptopurine; Middle Aged; Multivariate Analysis; Nutritional Status; Proportional Hazards Models; Retrospective Studies; Risk Factors; Serum Albumin; Serum Albumin, Human; Severity of Illness Index; Steroids; Time Factors; Treatment Failure; Tumor Necrosis Factor-alpha; Young Adult

PubMed ID






First Page


Last Page