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MONTREAL – Blood levels of a neutrophil receptor protein, CD64, proved to be a reliable, noninvasive marker of both Crohn’s disease activity and the risk for relapse from remission in children and adolescents in a pair of single-center studies with a total of 140 patients.
An elevation in blood levels of CD64, a marker for inflammation, in asymptomatic patients with Crohn’s disease “is a significant risk factor for treatment failure or complications during infliximab maintenance,” Phillip Minar, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. Although Dr. Minar acknowledged that larger validation studies are still needed, neutrophil CD64 levels can potentially serve as a “treat-to-target” biomarker of disease status in selected pediatric Crohn’s disease patients.
Dr. Minar cautioned that in some pediatric patients with Crohn’s disease CD64 is not an effective marker for inflammation and a change in their Crohn’s disease status. In his study, the sensitivity of an elevated CD64 level was 64% as a surrogate marker for mucosal damage seen with endoscopy.
“I get a CD64 level at the time we diagnose Crohn’s disease. If it is elevated, then I will follow it; if it is not elevated, then I won’t use it for that patient. It’s patient specific,” he explained in an interview.
Dr. Minar and his associates first established the prognostic value of elevated CD64 levels in patients with Crohn’s disease in a study with 208 pediatric patients with inflammatory bowel disease and 43 controls (Inflam Bowel Dis. 2014, Jun;20[6]:1037-48). His new validation study included 105 pediatric patients with Crohn’s disease, of whom 54 were newly diagnosed. Among the 51 previously diagnosed patients, 18 had inactive disease. The patients averaged 14 years old, and all 105 underwent endoscopy to directly examine their Crohn’s disease activity.
The results showed clear and statistically significant correlations among the average CD64 levels in the patients and the blinded endoscopic evaluations that categorized the patients as having inactive Crohn’s disease, mild disease, or moderate to severe disease. The results also suggested that a useful dichotomous cut point for CD64 was an index of 1. Among patients with a level above 1, diagnostic sensitivity for mucosal damage was 64% and specificity was 100%, he reported. In these studies as well as their routine practice, Dr. Minar and his associates use a commercially available immunoassay for quantifying blood levels of CD64.
The second study he reported on assessed the ability of CD64 levels to predict a patient’s status on infliximab (Remicade) maintenance treatment. This study enrolled 35 pediatric patients, who averaged about 15 years old, had been diagnosed with Crohn’s disease for an average of about 2 years and were in remission after having received at least four serial infliximab doses. During 1 year of follow-up, 15 patients relapsed and 21 remained in remission.
The researchers measured CD64 levels at baseline and found that, during the next year, those who had a CD64 index of less than 1 at baseline had a relapse rate of less than 40% during follow-up, while those with a CD64 index of 1 or greater at baseline had a relapse rate of more than 70% during follow-up, a statistically significant difference between the two subgroups. The analysis also showed that lower CD64 levels linked with higher trough levels of infliximab.
A multivariate analysis showed that a CD64 index level of 1 or greater at baseline linked with a statistically significant, 4.5-fold increased risk for relapse, compared with patients with a baseline CD64 level below 1. This analysis identified three additional significant correlates of an elevated risk for relapse: nonwhite race, a baseline serum albumin level of less than 3.9 g/dL, and a baseline infliximab serum level of less than 5 mcg/mL.
The CD64 test that his group has been using typically has a work week turnaround time of about an hour, and costs less than $100 per test per patient. Blood levels of CD64 are stable for 48 hours in the refrigerator, so specimens can sit over a weekend without compromising results. The Cincinnati group is planning to soon change to an in-house test that will cost about $10-$20 per test per patient, Dr. Minar said.
Dr. Minar had no relevant financial disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
We are in desperate need of more reliable biomarkers of disease activity in patients with Crohn’s disease. Identifying effective noninvasive biomarkers has been a holy grail that we have pursued for many years because what we currently have is imperfect. CD64 appears to be a very reliable and specific biomarker of disease activity.
I think pediatric gastroenterologists will pay attention to Dr. Minar’s report. The entire community is very interested in this and will be watching the evolution of the science behind CD64 assessment.
John A. Barnard, MD , is chief of pediatrics at Nationwide Children’s Hospital and professor and chairman of pediatrics at Ohio State University, both in Columbus. He had no relevant disclosures. He made these comments in an interview.
We are in desperate need of more reliable biomarkers of disease activity in patients with Crohn’s disease. Identifying effective noninvasive biomarkers has been a holy grail that we have pursued for many years because what we currently have is imperfect. CD64 appears to be a very reliable and specific biomarker of disease activity.
I think pediatric gastroenterologists will pay attention to Dr. Minar’s report. The entire community is very interested in this and will be watching the evolution of the science behind CD64 assessment.
John A. Barnard, MD , is chief of pediatrics at Nationwide Children’s Hospital and professor and chairman of pediatrics at Ohio State University, both in Columbus. He had no relevant disclosures. He made these comments in an interview.
We are in desperate need of more reliable biomarkers of disease activity in patients with Crohn’s disease. Identifying effective noninvasive biomarkers has been a holy grail that we have pursued for many years because what we currently have is imperfect. CD64 appears to be a very reliable and specific biomarker of disease activity.
I think pediatric gastroenterologists will pay attention to Dr. Minar’s report. The entire community is very interested in this and will be watching the evolution of the science behind CD64 assessment.
John A. Barnard, MD , is chief of pediatrics at Nationwide Children’s Hospital and professor and chairman of pediatrics at Ohio State University, both in Columbus. He had no relevant disclosures. He made these comments in an interview.
MONTREAL – Blood levels of a neutrophil receptor protein, CD64, proved to be a reliable, noninvasive marker of both Crohn’s disease activity and the risk for relapse from remission in children and adolescents in a pair of single-center studies with a total of 140 patients.
An elevation in blood levels of CD64, a marker for inflammation, in asymptomatic patients with Crohn’s disease “is a significant risk factor for treatment failure or complications during infliximab maintenance,” Phillip Minar, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. Although Dr. Minar acknowledged that larger validation studies are still needed, neutrophil CD64 levels can potentially serve as a “treat-to-target” biomarker of disease status in selected pediatric Crohn’s disease patients.
Dr. Minar cautioned that in some pediatric patients with Crohn’s disease CD64 is not an effective marker for inflammation and a change in their Crohn’s disease status. In his study, the sensitivity of an elevated CD64 level was 64% as a surrogate marker for mucosal damage seen with endoscopy.
“I get a CD64 level at the time we diagnose Crohn’s disease. If it is elevated, then I will follow it; if it is not elevated, then I won’t use it for that patient. It’s patient specific,” he explained in an interview.
Dr. Minar and his associates first established the prognostic value of elevated CD64 levels in patients with Crohn’s disease in a study with 208 pediatric patients with inflammatory bowel disease and 43 controls (Inflam Bowel Dis. 2014, Jun;20[6]:1037-48). His new validation study included 105 pediatric patients with Crohn’s disease, of whom 54 were newly diagnosed. Among the 51 previously diagnosed patients, 18 had inactive disease. The patients averaged 14 years old, and all 105 underwent endoscopy to directly examine their Crohn’s disease activity.
The results showed clear and statistically significant correlations among the average CD64 levels in the patients and the blinded endoscopic evaluations that categorized the patients as having inactive Crohn’s disease, mild disease, or moderate to severe disease. The results also suggested that a useful dichotomous cut point for CD64 was an index of 1. Among patients with a level above 1, diagnostic sensitivity for mucosal damage was 64% and specificity was 100%, he reported. In these studies as well as their routine practice, Dr. Minar and his associates use a commercially available immunoassay for quantifying blood levels of CD64.
The second study he reported on assessed the ability of CD64 levels to predict a patient’s status on infliximab (Remicade) maintenance treatment. This study enrolled 35 pediatric patients, who averaged about 15 years old, had been diagnosed with Crohn’s disease for an average of about 2 years and were in remission after having received at least four serial infliximab doses. During 1 year of follow-up, 15 patients relapsed and 21 remained in remission.
The researchers measured CD64 levels at baseline and found that, during the next year, those who had a CD64 index of less than 1 at baseline had a relapse rate of less than 40% during follow-up, while those with a CD64 index of 1 or greater at baseline had a relapse rate of more than 70% during follow-up, a statistically significant difference between the two subgroups. The analysis also showed that lower CD64 levels linked with higher trough levels of infliximab.
A multivariate analysis showed that a CD64 index level of 1 or greater at baseline linked with a statistically significant, 4.5-fold increased risk for relapse, compared with patients with a baseline CD64 level below 1. This analysis identified three additional significant correlates of an elevated risk for relapse: nonwhite race, a baseline serum albumin level of less than 3.9 g/dL, and a baseline infliximab serum level of less than 5 mcg/mL.
The CD64 test that his group has been using typically has a work week turnaround time of about an hour, and costs less than $100 per test per patient. Blood levels of CD64 are stable for 48 hours in the refrigerator, so specimens can sit over a weekend without compromising results. The Cincinnati group is planning to soon change to an in-house test that will cost about $10-$20 per test per patient, Dr. Minar said.
Dr. Minar had no relevant financial disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MONTREAL – Blood levels of a neutrophil receptor protein, CD64, proved to be a reliable, noninvasive marker of both Crohn’s disease activity and the risk for relapse from remission in children and adolescents in a pair of single-center studies with a total of 140 patients.
An elevation in blood levels of CD64, a marker for inflammation, in asymptomatic patients with Crohn’s disease “is a significant risk factor for treatment failure or complications during infliximab maintenance,” Phillip Minar, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. Although Dr. Minar acknowledged that larger validation studies are still needed, neutrophil CD64 levels can potentially serve as a “treat-to-target” biomarker of disease status in selected pediatric Crohn’s disease patients.
Dr. Minar cautioned that in some pediatric patients with Crohn’s disease CD64 is not an effective marker for inflammation and a change in their Crohn’s disease status. In his study, the sensitivity of an elevated CD64 level was 64% as a surrogate marker for mucosal damage seen with endoscopy.
“I get a CD64 level at the time we diagnose Crohn’s disease. If it is elevated, then I will follow it; if it is not elevated, then I won’t use it for that patient. It’s patient specific,” he explained in an interview.
Dr. Minar and his associates first established the prognostic value of elevated CD64 levels in patients with Crohn’s disease in a study with 208 pediatric patients with inflammatory bowel disease and 43 controls (Inflam Bowel Dis. 2014, Jun;20[6]:1037-48). His new validation study included 105 pediatric patients with Crohn’s disease, of whom 54 were newly diagnosed. Among the 51 previously diagnosed patients, 18 had inactive disease. The patients averaged 14 years old, and all 105 underwent endoscopy to directly examine their Crohn’s disease activity.
The results showed clear and statistically significant correlations among the average CD64 levels in the patients and the blinded endoscopic evaluations that categorized the patients as having inactive Crohn’s disease, mild disease, or moderate to severe disease. The results also suggested that a useful dichotomous cut point for CD64 was an index of 1. Among patients with a level above 1, diagnostic sensitivity for mucosal damage was 64% and specificity was 100%, he reported. In these studies as well as their routine practice, Dr. Minar and his associates use a commercially available immunoassay for quantifying blood levels of CD64.
The second study he reported on assessed the ability of CD64 levels to predict a patient’s status on infliximab (Remicade) maintenance treatment. This study enrolled 35 pediatric patients, who averaged about 15 years old, had been diagnosed with Crohn’s disease for an average of about 2 years and were in remission after having received at least four serial infliximab doses. During 1 year of follow-up, 15 patients relapsed and 21 remained in remission.
The researchers measured CD64 levels at baseline and found that, during the next year, those who had a CD64 index of less than 1 at baseline had a relapse rate of less than 40% during follow-up, while those with a CD64 index of 1 or greater at baseline had a relapse rate of more than 70% during follow-up, a statistically significant difference between the two subgroups. The analysis also showed that lower CD64 levels linked with higher trough levels of infliximab.
A multivariate analysis showed that a CD64 index level of 1 or greater at baseline linked with a statistically significant, 4.5-fold increased risk for relapse, compared with patients with a baseline CD64 level below 1. This analysis identified three additional significant correlates of an elevated risk for relapse: nonwhite race, a baseline serum albumin level of less than 3.9 g/dL, and a baseline infliximab serum level of less than 5 mcg/mL.
The CD64 test that his group has been using typically has a work week turnaround time of about an hour, and costs less than $100 per test per patient. Blood levels of CD64 are stable for 48 hours in the refrigerator, so specimens can sit over a weekend without compromising results. The Cincinnati group is planning to soon change to an in-house test that will cost about $10-$20 per test per patient, Dr. Minar said.
Dr. Minar had no relevant financial disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point: Results from two studies further validated neutrophil CD64 as a highly specific biomarker for Crohn’s disease severity in children and adolescents and suggested that CD64 could serve as a treat-to-target guide for infliximab treatment.
Major finding: During infliximab maintenance, relapses occurred in fewer than 40% of pediatric Crohn’s disease patients with low CD64 and in more than 70% with high CD64.
Data source: A single-center study of 105 pediatric patients with Crohn’s disease to assess disease severity correlates, and 35 patients in remission on infliximab to assess predicted efficacy.
Disclosures: Dr. Minar had no relevant financial disclosures.