Managing Crohn’s disease (CD) requires more than following patient symptoms; biomarkers such as fecal calprotectin, CRP, and others may offer earlier insights and may guide more effective treatment. From reducing delays in diagnosis to supporting personalized therapies, biomarker-driven care is helping to reshape the future of inflammatory bowel disease management.

Biomarkers are an important adjunct to the care of patients with CD. One of the difficult parts of managing CD effectively is that there is often a lengthy delay in diagnosis. In fact, the average delay in diagnosis is 2 years. The initial symptoms of CD are often abdominal pain and diarrhea, which are very common and are often associated with irritable bowel syndrome. A primary care provider may not even think that a patient presenting with these symptoms has CD, and this is a very important potential place for biomarkers. An elevation of fecal calprotectin or CRP, once enteric infection has been excluded, would demonstrate a reasonably high likelihood of CD and would warrant a referral for further evaluation. However, there is not any specific blood or stool biomarker at this time that can definitively establish a diagnosis of CD. It is still a clinical diagnosis comprised of symptoms plus objective findings on ileocolonoscopy, substantiated by histopathology from biopsies and sometimes cross-sectional imaging.

<br>

We are really excited about using biomarkers to help us move into the treat-to-target era of managing CD. We know that, in many patients, there is a disconnect between the presence of symptoms and the presence of inflammation, and it is the inflammation that drives complications such as strictures and fistulas, often leading to surgeries, which, in time, may lead to disability. Measuring biomarkers such as fecal calprotectin and CRP on a recurring basis can give us a noninvasive way to detect when a patient deviates from normal to elevated levels, and then we can evaluate the patient further to determine if there is an increase in bowel inflammation that requires treatment modification.

<br>

The benefits of this approach were demonstrated in the CALM trial. CALM compared 2 groups: 1 group escalated treatment based solely on symptoms, while the other group added fecal calprotectin and CRP into the decision-making process. Both the clinical and endoscopic outcomes of patients who had biomarkers incorporated into their treatment were superior. However, it is important to note that up to 25% of patients cannot produce CRP in response to CD-related inflammation, and, in isolated ileal CD, the sensitivity of both fecal calprotectin and CRP is lower.

<br>

There is a lot of excitement surrounding the potential of biomarkers that could help us predict the likelihood of response to a given medication, especially since, on average, current medications only get approximately 45% of people into remission after 1 year. For example, in the ARTEMIS-UC trial, a genetics-based diagnostic test was designed to identify patients with ulcerative colitis who had an increased likelihood of response to tulisokibart, an experimental IL-23p19 antibody therapy. While the initial results in the first study cohort were promising, the distinction was not as notable in the second cohort of this study.

<br>

We are also seeing work being done on prognostic biomarkers to help predict disease course. Tools such as CDPATH combine clinical, serologic, and genetics data to give patients an awareness of how aggressive their disease might be and whether early, more intensive treatment would make sense for them.

<br>

Future biomarkers that are being investigated include LRG, which has been shown to correlate with endoscopic disease activity, and OSM, which may be associated with poor response to anti-TNF therapy and worse outcomes when highly expressed.