Genetic and Inflammatory Biomarkers Classify Small Intestine Inflammation in Asymptomatic First-degree Relatives of Patients With Crohn's Disease.

BACKGROUND & AIMS: Relatives of individuals with Crohn's disease (CD) carry CD-associated genetic variants and are often exposed to environmental factors that increase their risk for this disease. We aimed to estimate the utility of genotype, smoking status, family history, and biomarkers can calculate risk in asymptomatic first-degree relatives of patients with CD. METHODS: We recruited 480 healthy first-degree relatives (full siblings, offspring or parents) of patients with CD through the Guy's and St Thomas' NHS Foundation Trust and from members of Crohn's and Colitis, United Kingdom. DNA samples were genotyped using the Immunochip. We calculated a risk score for 454 participants, based on 72 genetic variants associated with CD, family history, and smoking history. Participants were assigned to highest and lowest risk score quartiles. We assessed pre-symptomatic inflammation by capsule endoscopy and measured 22 markers of inflammation in stool and serum samples (reference standard). Two machine-learning classifiers (elastic net and random forest) were used to assess the ability of the risk factors and biomarkers to identify participants with small intestinal inflammation in the same dataset. RESULTS: The machine-learning classifiers identified participants with pre-symptomatic intestinal inflammation: elastic net (area under the curve, 0.80; 95% CI, 0.62-0.98) and random forest (area under the curve, 0.87; 95% CI, 0.75-1.00). The elastic net method identified 3 variables that can be used to calculate odds for intestinal inflammation: combined family history of CD (odds ratio, 1.31), genetic risk score (odds ratio, 1.14), and fecal calprotectin (odds ratio, 1.04). These same 3 variables were among the 5 factors associated with intestinal inflammation in the random forest model. CONCLUSION: Using machine learning classifiers, we found that genetic variants associated with CD, family history, and fecal calprotectin together identify individuals with pre-symptomatic intestinal inflammation who are therefore at risk for CD. A tool for detecting people at risk for CD before they develop symptoms would help identify the individuals most likely to benefit from early intervention.

The impact of an inflammatory bowel disease nurse-led biologics service.

INTRODUCTION: Southampton General Hospital provides inflammatory bowel disease (IBD) services for a population of 650 000. Biological agents have impacted hugely on IBD but are costly drugs requiring careful supervision. These challenges led us to develop a specialist nurse-led biologics service to improve patient care. METHOD: A 2010 case note audit highlighted areas for improvement in monitoring biologics and follow-up. A business case was developed to establish an IBD nurse to ensure identification and appropriate screening, education and review of biologics patients. A gain share was agreed with the local Care Commissioning Group (CCG) and £60 000 invested. Outcomes were reaudited in 2014. RESULTS: Biologic use has grown rapidly from 90 patients in 2011 to 330 in 2014. All records are now kept in a centralised database. Infection screening improved from 79% to 100%. In 2014, 96% of patients had follow-up ≤4 months post-induction to assess response, but two patients were seen at 7 months. 80% were followed up again at 9-12 months (100% at 9-14 months), all with treatment decisions. The initial investment was recouped via commissioners funding 368 additional outpatient appointments and 35 colonoscopies. Savings represented 15% total yearly biologic costs. CONCLUSIONS: The introduction of the IBD biologics nurse-led service resulted in significant gains in care quality and costs. The need for improved follow-up of patients on biologics reflects increased pressures on clinic resources across the country. With continued biologics expansion, the introduction of a biologics nurse has provided invaluable support to patients and the IBD team at Southampton General Hospital.