AGA clinical practice guideline affirms role of biomarkers in Crohn’s disease management

A new Clinical Practice Guideline from American Gastroenterological Association points to a stronger and better defined role for fecal and blood biomarkers in the management of Crohn’s disease, offering the most specific evidence-based recommendations yet for the use of fecal calprotectin (FCP) and serum C-reactive protein (CRP) in assessing disease activity.

Repeated monitoring with endoscopy allows for an objective assessment of inflammation and mucosal healing compared with symptoms alone. However, relying solely on endoscopy to guide management is an approach “limited by cost and resource utilization, invasiveness, and reduced patient acceptability,” wrote guideline authors on behalf of the AGA Clinical Guidelines Committee. The guideline was published online Nov. 17 in Gastroenterology.

“Use of biomarkers is no longer considered experimental and should be an integral part of IBD care and monitoring,” said Ashwin Ananthakrishnan, MBBS, MPH, a gastroenterologist with Massachusetts General Hospital in Boston and first author of the guideline. “We need further studies to define their optimal longitudinal use, but at a given time point, there is now abundant evidence that biomarkers provide significant incremental benefit over symptoms alone in assessing a patient’s status.”

Using evidence from randomized controlled trials and observational studies, and applying it to common clinical scenarios, there are conditional recommendations on the use of biomarkers in patients with established, diagnosed disease who were asymptomatic, symptomatic, or in surgically induced remission. Those recommendations, laid out in a detailed Clinical Decision Support Tool, include the following:

For asymptomatic patients: Check CRP and FCP every 6-12 months. Patients with normal levels, and who have endoscopically confirmed remission within the last 3 years without any subsequent change in symptoms or treatment, need not undergo endoscopy and can be followed with biomarker and clinical checks alone. If CRP or FCP are elevated (defined as CRP ≥ 5 mg/L, FCP ≥ 150 mcg/g), consider repeating biomarkers and/or performing endoscopic assessment of disease activity before adjusting treatment.

For mildly symptomatic patients: Role of biomarker testing may be limited and endoscopic or radiologic assessment may be required to assess active inflammation given the higher rate of false positive and false negative results with biomarkers in this population.

For patients with more severe symptoms: Elevated CRP or FCP can be used to guide treatment adjustment without endoscopic confirmation in certain situations. Normal levels may be false negative and should be confirmed by endoscopic assessment of disease activity.

For patients in surgically induced remission with a low likelihood of recurrence: FCP levels below 50 mcg/g can be used in lieu of routine endoscopic assessment within the first year after surgery. Higher FCP levels should prompt endoscopic assessment.

For patients in surgically induced remission with a high risk of recurrence: Do not rely on biomarkers. Perform endoscopic assessment.

All recommendations were deemed of low to moderate certainty based on results from randomized clinical trials and observational studies that utilized these biomarkers in patients with Crohn’s disease. Citing a dearth of quality evidence, the guideline authors determined they could not make recommendations on the use of a third proprietary biomarker — the endoscopic healing index (EHI).

Recent AGA Clinical Practice Guidelines on the role of biomarkers in ulcerative colitis, published in March, also support a strong role for fecal and blood biomarkers, determining when these can be used to avoid unneeded endoscopic assessments. However, in patients with Crohn’s disease, symptoms correlate less well with endoscopic activity.

As a result, “biomarker performance was acceptable only in asymptomatic individuals who had recently confirmed endoscopic remission; in those without recent endoscopic assessment, test performance was suboptimal.” In addition, the weaker correlation between symptoms and endoscopic activity in Crohn’s “reduced the utility of biomarker measurement to infer disease activity in those with mild symptoms.”

The guidelines were fully funded by the AGA Institute. The authors disclosed a number of potential conflicts of interest, including receiving research grants, as well as consulting and speaking fees, from pharmaceutical companies.

A new Clinical Practice Guideline from American Gastroenterological Association points to a stronger and better defined role for fecal and blood biomarkers in the management of Crohn’s disease, offering the most specific evidence-based recommendations yet for the use of fecal calprotectin (FCP) and serum C-reactive protein (CRP) in assessing disease activity.

Repeated monitoring with endoscopy allows for an objective assessment of inflammation and mucosal healing compared with symptoms alone. However, relying solely on endoscopy to guide management is an approach “limited by cost and resource utilization, invasiveness, and reduced patient acceptability,” wrote guideline authors on behalf of the AGA Clinical Guidelines Committee. The guideline was published online Nov. 17 in Gastroenterology.

“Use of biomarkers is no longer considered experimental and should be an integral part of IBD care and monitoring,” said Ashwin Ananthakrishnan, MBBS, MPH, a gastroenterologist with Massachusetts General Hospital in Boston and first author of the guideline. “We need further studies to define their optimal longitudinal use, but at a given time point, there is now abundant evidence that biomarkers provide significant incremental benefit over symptoms alone in assessing a patient’s status.”

Using evidence from randomized controlled trials and observational studies, and applying it to common clinical scenarios, there are conditional recommendations on the use of biomarkers in patients with established, diagnosed disease who were asymptomatic, symptomatic, or in surgically induced remission. Those recommendations, laid out in a detailed Clinical Decision Support Tool, include the following:

For asymptomatic patients: Check CRP and FCP every 6-12 months. Patients with normal levels, and who have endoscopically confirmed remission within the last 3 years without any subsequent change in symptoms or treatment, need not undergo endoscopy and can be followed with biomarker and clinical checks alone. If CRP or FCP are elevated (defined as CRP ≥ 5 mg/L, FCP ≥ 150 mcg/g), consider repeating biomarkers and/or performing endoscopic assessment of disease activity before adjusting treatment.

For mildly symptomatic patients: Role of biomarker testing may be limited and endoscopic or radiologic assessment may be required to assess active inflammation given the higher rate of false positive and false negative results with biomarkers in this population.

For patients with more severe symptoms: Elevated CRP or FCP can be used to guide treatment adjustment without endoscopic confirmation in certain situations. Normal levels may be false negative and should be confirmed by endoscopic assessment of disease activity.

For patients in surgically induced remission with a low likelihood of recurrence: FCP levels below 50 mcg/g can be used in lieu of routine endoscopic assessment within the first year after surgery. Higher FCP levels should prompt endoscopic assessment.

For patients in surgically induced remission with a high risk of recurrence: Do not rely on biomarkers. Perform endoscopic assessment.

All recommendations were deemed of low to moderate certainty based on results from randomized clinical trials and observational studies that utilized these biomarkers in patients with Crohn’s disease. Citing a dearth of quality evidence, the guideline authors determined they could not make recommendations on the use of a third proprietary biomarker — the endoscopic healing index (EHI).

Recent AGA Clinical Practice Guidelines on the role of biomarkers in ulcerative colitis, published in March, also support a strong role for fecal and blood biomarkers, determining when these can be used to avoid unneeded endoscopic assessments. However, in patients with Crohn’s disease, symptoms correlate less well with endoscopic activity.

As a result, “biomarker performance was acceptable only in asymptomatic individuals who had recently confirmed endoscopic remission; in those without recent endoscopic assessment, test performance was suboptimal.” In addition, the weaker correlation between symptoms and endoscopic activity in Crohn’s “reduced the utility of biomarker measurement to infer disease activity in those with mild symptoms.”

The guidelines were fully funded by the AGA Institute. The authors disclosed a number of potential conflicts of interest, including receiving research grants, as well as consulting and speaking fees, from pharmaceutical companies.

A new Clinical Practice Guideline from American Gastroenterological Association points to a stronger and better defined role for fecal and blood biomarkers in the management of Crohn’s disease, offering the most specific evidence-based recommendations yet for the use of fecal calprotectin (FCP) and serum C-reactive protein (CRP) in assessing disease activity.

Repeated monitoring with endoscopy allows for an objective assessment of inflammation and mucosal healing compared with symptoms alone. However, relying solely on endoscopy to guide management is an approach “limited by cost and resource utilization, invasiveness, and reduced patient acceptability,” wrote guideline authors on behalf of the AGA Clinical Guidelines Committee. The guideline was published online Nov. 17 in Gastroenterology.

“Use of biomarkers is no longer considered experimental and should be an integral part of IBD care and monitoring,” said Ashwin Ananthakrishnan, MBBS, MPH, a gastroenterologist with Massachusetts General Hospital in Boston and first author of the guideline. “We need further studies to define their optimal longitudinal use, but at a given time point, there is now abundant evidence that biomarkers provide significant incremental benefit over symptoms alone in assessing a patient’s status.”

Using evidence from randomized controlled trials and observational studies, and applying it to common clinical scenarios, there are conditional recommendations on the use of biomarkers in patients with established, diagnosed disease who were asymptomatic, symptomatic, or in surgically induced remission. Those recommendations, laid out in a detailed Clinical Decision Support Tool, include the following:

For asymptomatic patients: Check CRP and FCP every 6-12 months. Patients with normal levels, and who have endoscopically confirmed remission within the last 3 years without any subsequent change in symptoms or treatment, need not undergo endoscopy and can be followed with biomarker and clinical checks alone. If CRP or FCP are elevated (defined as CRP ≥ 5 mg/L, FCP ≥ 150 mcg/g), consider repeating biomarkers and/or performing endoscopic assessment of disease activity before adjusting treatment.

For mildly symptomatic patients: Role of biomarker testing may be limited and endoscopic or radiologic assessment may be required to assess active inflammation given the higher rate of false positive and false negative results with biomarkers in this population.

For patients with more severe symptoms: Elevated CRP or FCP can be used to guide treatment adjustment without endoscopic confirmation in certain situations. Normal levels may be false negative and should be confirmed by endoscopic assessment of disease activity.

For patients in surgically induced remission with a low likelihood of recurrence: FCP levels below 50 mcg/g can be used in lieu of routine endoscopic assessment within the first year after surgery. Higher FCP levels should prompt endoscopic assessment.

For patients in surgically induced remission with a high risk of recurrence: Do not rely on biomarkers. Perform endoscopic assessment.

All recommendations were deemed of low to moderate certainty based on results from randomized clinical trials and observational studies that utilized these biomarkers in patients with Crohn’s disease. Citing a dearth of quality evidence, the guideline authors determined they could not make recommendations on the use of a third proprietary biomarker — the endoscopic healing index (EHI).

Recent AGA Clinical Practice Guidelines on the role of biomarkers in ulcerative colitis, published in March, also support a strong role for fecal and blood biomarkers, determining when these can be used to avoid unneeded endoscopic assessments. However, in patients with Crohn’s disease, symptoms correlate less well with endoscopic activity.

As a result, “biomarker performance was acceptable only in asymptomatic individuals who had recently confirmed endoscopic remission; in those without recent endoscopic assessment, test performance was suboptimal.” In addition, the weaker correlation between symptoms and endoscopic activity in Crohn’s “reduced the utility of biomarker measurement to infer disease activity in those with mild symptoms.”

The guidelines were fully funded by the AGA Institute. The authors disclosed a number of potential conflicts of interest, including receiving research grants, as well as consulting and speaking fees, from pharmaceutical companies.