Biological Changes Apparent Years Before CD Diagnosis

Widespread hematological and biochemical changes occur up to 8 years before the diagnosis of Crohn’s disease (CD) and up to 3 years before the diagnosis of ulcerative colitis (UC), according to a study published online ahead of print in Cell Reports Medicine.

Previous estimates had placed the preclinical phase of inflammatory bowel disease (IBD) at 1 to 5 years before diagnosis.

“These results indicate that disease initiation is likely to begin far earlier than previously thought, especially in CD,” wrote corresponding author Tine Jess, MD, DMSc, Aalborg University, Copenhagen, Denmark, and study coauthors. “This has important implications for the future development of strategies aimed at preventing the onset of disease and conversely highlights a considerable window of opportunity that could be targeted pharmacologically for early therapy or by addressing modifiable risk factors (eg, smoking and diet).”

The study compared 17 hematological and biochemical parameters in blood taken up to 10 years before diagnosis in more than 20,000 patients with IBD and 4.6 million potential population-based controls.

Differences in C-reactive protein, leukocytes, neutrophils, monocytes, platelets, hemoglobin, iron, and albumin emerged as early as 8 years before CD diagnosis and 3 years before UC diagnosis, according to the study. Despite significantly differing from controls, however, the detected changes were within normal ranges, with the exception of fecal calprotectin.

“Since most of the preclinical changes were not due to abnormally high or low test results, we concluded that these would not be individually useful as diagnostic tools,” researchers wrote. “However, we also reasoned that it might be possible to build predictive classifiers by considering these in combination.”

Predictive models that combined C-reactive protein, neutrophil, monocyte, platelet, hemoglobin, and eosinophil levels showed modest predictive performance in an independent validation set, which worsened further out from diagnosis.

“In any case, it seems likely that better biomarkers will be needed to fulfill the potential of targeting the preclinical phase of IBD. Incorporating additional predictors and investigating more advanced learning algorithms, including neural networks, could improve model performance and should be the focus of future work,” researchers wrote.

Reference:
Vestergaard MV, Allin KH, Poulsen GJ, Lee JC, Jess T. Characterizing the pre-clinical phase of inflammatory bowel disease. Cell Rep Med. Published online November 21, 2023. doi:10.1016/j.xcrm.2023.101263