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

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.

Persistent Reactive Thrombocytosis May Increase the Risk of Coronary Artery Disease Among Inflammatory Bowel Disease Patients.

BACKGROUND: IBD patients are at increased risk of coronary artery disease in the absence of traditional risk factors. However, the disease-related risk factors remain poorly understood although increased inflammation seems to increase cardiovascular disease risk in IBD. Thrombocytes are involved in the pathogenesis of coronary artery disease, and a subset of IBD patients have reactive thrombocytosis. AIM: The aim of our study was to investigate the effect of persistent reactive thrombocytosis on the development of coronary artery disease in IBD. METHODS: We evaluated a retrospective cohort of 2525 IBD patients who were evaluated at the Henry Ford hospital from 2000 to 2004. We performed a case-control study comparing patients with persistent thrombocytosis and patients without persistent thrombocytosis. Cases (n = 36) and controls (n = 72) were matched for age and gender. Coronary artery disease incidence was compared between the two groups. RESULTS: Cases (n = 36) and controls (n = 72) were matched for age and gender. Cases and controls were similar in age at onset of IBD (41.5 vs. 35.5, p value 0.11) and smoking status (33.3 vs. 27.8%, p value 0.66). Persistent thrombocytosis was less common among Caucasian patients (44.44 vs. 62.5%, p value 0.09) and more common in patients who had exposure to steroids during the study follow-up period. Coronary artery disease occurred in 13 (36.1%) patients with persistent thrombocytosis compared to only seven (9.7%) patients in the control group. CONCLUSIONS: Persistent reactive thrombocytosis among IBD patients is associated with increased risk of coronary artery disease. Further studies should characterize the clinical and molecular associations of this phenomenon and determine appropriate therapeutic measures.

Effect of Inflammatory Bowel Disease-Related Characteristics and Treatment Interventions on Cardiovascular Disease Incidence.

BACKGROUND: An association between inflammatory bowel disease (IBD) and cardiovascular diseases has been shown in multiple studies. However, little is known about the effect of IBD-related characteristics on cardiovascular events. METHODS: The authors conducted a retrospective, nested case-control study of IBD patients who presented to the institution from 2000 to 2004, allowing for a 10-year follow-up period. One hundred eleven patients who developed cardiovascular events (cases) and 222 patients who did not develop cardiovascular events (cases) were included in the study after matching for Framingham cardiovascular risk score (2008). Relationships between predictor variables and cardiovascular outcome were assessed by conditional logistic regression. RESULTS: The cases and controls were similar in age, gender, smoking and cholesterol level. There was no difference in disease subtype (ulcerative colitis or Crohn's disease). On conditional logistic regression, thiopurine treatment (odds ratio [OR]: 0.42, 95% confidence interval [CI]: 0.19-0.87; P = 0.02) was associated with decreased cardiovascular events and tumor necrosis factor alpha antagonist use (OR: 2.63, 95% CI: 1.49-4.63; P = 0.001) was associated with increased cardiovascular events. Although not statistically significant, disease-related surgery (OR: 0.57, 95% CI: 0.32-1.02; P = 0.06) was associated with decreased cardiovascular events and disease-related hospitalization (OR: 1.58, 95% CI: 0.96-2.57; P = 0.07) was associated with increased incidence of cardiovascular disorders. CONCLUSIONS: The authors observed decreased incidence of cardiovascular diseases in patients with IBD who were treated with thiopurines and increased incidence of cardiovascular outcomes among patients treated with tumor necrosis factor alpha antagonist.