To derive the model, Dr. Wang and colleagues used a large multicenter IBD cohort.
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They first analyzed clinical factors such as gender, age at diagnosis, family and smoking history, and location and behavior of the disease. Participants were then genotyped using the Illumina gene chip, and the researchers identified SNPs associated with early surgery. They next searched for genetic risk profiles using logical regression, a machine learning algorithm, ultimately identifying three different profiles.
The risk score for early Crohn's disease surgery based on combined clinical and genetic predictors demonstrates a sensitivity and specificity of 72 and 82 percent, respectively.
Patients with Crohn's disease who carry 1, 2 or 3 newly developed genetic risk profiles are more likely to need early surgery after diagnosis. Of patients with Crohn's disease, — 42 percent — had early surgery.
Early age at diagnosis, ileal disease, complicated CD, and one or more of the three genetic risk profiles were associated with surgery in these patients. The mean follow-up was 6. Wang says. The score had a sensitivity and specificity of 72 and 82 percent, respectively.
The study results were presented at the annual meeting of the American College of Gastroenterology and published in the October American Journal of Gastroenterology supplement. But it became apparent that the longer inflammation was uncontrolled, the greater the likelihood of scar tissue formation, blockage and subsequent bowel resection. So the new approach is to be more aggressive at the very beginning of the disease course — the step-down strategy — to prevent bad consequences down the road.
This model can help guide treatment by determining which patients will need more-aggressive treatment sooner," Dr. Wang explains. He believes the predictive profile can become clinically practicable once independently validated.
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Yamazaki K, et al. Human Molecular Genetics. Jostins L, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
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