Biomarker Monitoring Should Come First for Ulcerative Colitis

The American Gastroenterological Association is recommending biomarker tests to first determine if endoscopy is necessary.

Some ulcerative colitis patients may not need to be monitored as often with invasive endoscopies, according to new guidelines from the American Gastroenterological Association (AGA).

Published this week in the journal Gastroenterology, the guidelines highlight how biomarker monitoring via noninvasive blood and stool tests can provide a valuable way to monitor people whose ulcerative colitis (UC) is in remission, as well as in some with current UC symptoms.

Because ulcerative colitis causes inflammation and sores, or ulcers, in the large intestine, doctors may use an endoscope — a lighted, flexible tube with a camera at the end — to examine that part of the gastrointestinal (GI) tract.

There are two types of endoscopies used during ulcerative colitis testing, according to the Crohn's & Colitis Foundation. A sigmoidoscopy provides an examination of inflammation in the lower colon and rectum, while a total colonoscopy provides an examination of the entire colon.

While endoscopy has been the gold standard for monitoring ulcerative colitis and detecting bowel inflammation, the authors of the new guidelines point out that this type of assessment is invasive, expensive, and often takes weeks to schedule.

"Fecal and blood testing, however, can [provide] objective evidence about inflammation, worsening inflammation, and improved inflammation without having to necessarily subject the patient to invasive procedures, such as colonoscopy or similar insertion of a scope into an orifice of the body," says gastroenterologist Russell Cohen, MD, director of the UChicago Medicine Inflammatory Bowel Disease Center, who was not involved in writing the guidelines. These tests can reveal if medications are working and if the disease is being well-managed.

The AGA recommendations focus on three specific biomarkers that can provide accurate insights into ulcerative colitis disease activity: fecal calprotectin and fecal lactoferrin, detected in stool, and serum C-reactive protein (CRP), detected in blood.

The new guidelines suggest that biomarker testing should be the first step to determine the need for endoscopic assessment in patients who have symptomatic UC. They also advise biomarker monitoring every 6 to 12 months in UC patients in symptomatic remission.

Stool tests are favored over blood tests, say the authors, because they are more sensitive, which allows them to detect even mild inflammation. They’re also more specific, since the measurements would be elevated only from intestinal inflammation rather than any incidental ongoing medical problem, such as a respiratory infection.

For patients in symptomatic remission who have normal biomarkers, the AGA recommends continuing biomarker monitoring but avoiding routine endoscopic assessment.

The guidelines also indicate that endoscopic assessment should be avoided for patients with moderate to severe symptoms and elevated biomarkers.

"If there are severe symptoms and elevated biomarkers, this confirms the symptoms are from active ulcerative colitis," says guidelines author Ashwin N. Ananthakrishnan, MBBS, MPH, a gastroenterologist with Massachusetts General Hospital in Boston. "One does not need to wait for an endoscopy in this setting and should initiate treatment early without delay."

The AGA continues to endorse endoscopic assessment in the following scenarios:

"Biomarkers are imperfect, and some patients, despite significant inflammation, may not have a rise in biomarkers," says guidelines author Siddharth Singh, MD, a gastroenterologist with the University of California in San Diego. "In these situations, endoscopy can help gauge inflammation and also help evaluate potential other causes of symptoms, like specific infections."

Dr. Ananthakrishnan adds that endoscopy can help determine the appropriate level of treatment.

"If the symptoms are not from the underlying UC, there is risk of inappropriate overtreatment," he says. "On the other hand, if the biomarker is falsely normal, there is risk of inappropriate undertreatment. That's why an endoscopic assessment is needed."

Ultimately, the decision to use endoscopy should be up to the physician, according to Dr. Cohen.

"There are cases where I see the data but I still want to look with the scope, and that should be allowed — it's really up to the judgment of the doctor," he says.

While the AGA recommends that a monitoring strategy should include biomarkers and symptoms rather than symptoms alone, the association concluded that more evidence was needed before definitively endorsing a biomarker-based monitoring strategy over endoscopy-based monitoring.

When it comes to paying for biomarker tests, there is significant variability in coverage across different healthcare plans, according to the authors.

"Stool tests are sometimes not covered by insurance and deemed to be ‘experimental’ despite extensive data," says Dr. Singh. "Through these guidelines, we hope to change that so that these tests are routinely covered by insurance. That will be a win for patients, providers, and our overburdened healthcare system."

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