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Causes of recurrent pediatric pancreatitis start to emerge
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Overall, 17 of 83 patients (20%) had recurrent acute pancreatitis, but among six patients with a genetic cause, five had recurrences.
Data source: Eighty-three patients enrolled in INSPPIRE, an international consortium formed to prospectively study pediatric pancreatitis.
Disclosures: Dr. Sweeny had no disclosures.
Frailty stratifies pediatric liver disease severity
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: The pediatric frailty score identified patients with end-stage liver disease with sensitivity of 47% and specificity of 98%.
Data source: A series of 71 pediatric patients with liver disease compiled from 17 U.S. and Canadian centers.
Disclosures: Dr. Lurz had no relevant financial disclosures.
Vedolizumab shows safety, efficacy for pediatric IBD
MONTREAL – Vedolizumab, 2 years out from its entry onto the U.S. market as an option for treating adults with inflammatory bowel disease, also has shown early safety and efficacy in 52 pediatric patients with ulcerative colitis or Crohn’s disease.
Retrospective review of a patients series assembled from three U.S. centers showed 13 (76%) ulcerative colitis patients in remission among 17 treated and followed for 14 weeks, the study’s primary outcome. Among 24 Crohn’s disease patients treated and followed for 14 weeks, 10 (42%) had remissions, Namita Singh, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
Treatment with vedolizumab (Entyvio), an anti-integrin with highly gut-specific activity that limits its systemic effects, was especially potent for the five patients in the series who were naive to treatment with an anti–tumor necrosis factor (TNF) agent. All five patients were in remission at 14 weeks, said Dr. Singh, a pediatric gastroenterologist at Cedars-Sinai Medical Center, Los Angeles.
“From this and other data it seems like there is a potential role for vedolizumab as first-line treatment” for selected patients, Dr. Singh said in an interview. “The attraction of vedolizumab is its gut selectivity.”
The American Gastroenterological Association lists vedolizumab as an equal alternative to an anti-TNF agent in its recommended algorithm for treating ulcerative colitis, but vedolizumab is not mentioned in the association’s posted guidance for treating Crohn’s disease. ”Prospective studies are needed” to generate more definitive evidence on how to use vedolizumab, she acknowledged, but added that pediatric gastroenterological societies “need to come up with guidelines on where to place vedolizumab.”Dr. Singh said she discusses with patients and their families the potential risks and benefits of the various treatment options available when inflammatory bowel disease (IBD) doesn’t respond to mesalamine: an anti-TNF agent, an immunomodulator like methotrexate or azathioprine, or vedolizumab. One important issue when deciding which drug class to try first is the cost of treatment and whether it will be covered by insurance.
The combined series included pediatric IBD patients less than 18 years old, with an actual median age of just under 15 years. They had been diagnosed with ulcerative colitis or Crohn’s disease for a median of 3 years. The 30 Crohn’s disease patients had received a median of two anti-TNF agents prior to starting vedolizumab, while the ulcerative colitis patients had received a median of one anti-TNF drug before vedolizumab. Three-quarters of the patients received the adult dose of 300 mg per infusion. A fifth of the patients received a dosage of 6 mg/kg, and the remaining patients received 5 mg/kg.
Although the 24 Crohn’s disease patients followed through 14 weeks of therapy had a 42% remission rate, the remission rate jumped sharply to more than 70% among the 11 patients followed to 30 weeks.
One limitation to vedolizumab is its relatively slow onset of action, slower than anti-TNF agents, which makes vedolizumab less suitable for patients with acute, severe colitis, although short-term improvement of acute colitis can be achieved with a corticosteroid when starting a patient on vedolizumab, Dr. Singh said. A trial currently underway is collecting prospective data on vedolizumab in pediatric IBD patients that could result in pediatric labeling for the drug, she added.
Until those data are available, current experience suggests vedolizumab “is good for ulcerative colitis patients,” she said. “Our data encourage us to continue” offering vedolizumab to selected pediatric IBD patients.
Dr. Singh has been a consultant to Janssen and Prometheus and received grant support from Janssen.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Vedolizumab, 2 years out from its entry onto the U.S. market as an option for treating adults with inflammatory bowel disease, also has shown early safety and efficacy in 52 pediatric patients with ulcerative colitis or Crohn’s disease.
Retrospective review of a patients series assembled from three U.S. centers showed 13 (76%) ulcerative colitis patients in remission among 17 treated and followed for 14 weeks, the study’s primary outcome. Among 24 Crohn’s disease patients treated and followed for 14 weeks, 10 (42%) had remissions, Namita Singh, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
Treatment with vedolizumab (Entyvio), an anti-integrin with highly gut-specific activity that limits its systemic effects, was especially potent for the five patients in the series who were naive to treatment with an anti–tumor necrosis factor (TNF) agent. All five patients were in remission at 14 weeks, said Dr. Singh, a pediatric gastroenterologist at Cedars-Sinai Medical Center, Los Angeles.
“From this and other data it seems like there is a potential role for vedolizumab as first-line treatment” for selected patients, Dr. Singh said in an interview. “The attraction of vedolizumab is its gut selectivity.”
The American Gastroenterological Association lists vedolizumab as an equal alternative to an anti-TNF agent in its recommended algorithm for treating ulcerative colitis, but vedolizumab is not mentioned in the association’s posted guidance for treating Crohn’s disease. ”Prospective studies are needed” to generate more definitive evidence on how to use vedolizumab, she acknowledged, but added that pediatric gastroenterological societies “need to come up with guidelines on where to place vedolizumab.”Dr. Singh said she discusses with patients and their families the potential risks and benefits of the various treatment options available when inflammatory bowel disease (IBD) doesn’t respond to mesalamine: an anti-TNF agent, an immunomodulator like methotrexate or azathioprine, or vedolizumab. One important issue when deciding which drug class to try first is the cost of treatment and whether it will be covered by insurance.
The combined series included pediatric IBD patients less than 18 years old, with an actual median age of just under 15 years. They had been diagnosed with ulcerative colitis or Crohn’s disease for a median of 3 years. The 30 Crohn’s disease patients had received a median of two anti-TNF agents prior to starting vedolizumab, while the ulcerative colitis patients had received a median of one anti-TNF drug before vedolizumab. Three-quarters of the patients received the adult dose of 300 mg per infusion. A fifth of the patients received a dosage of 6 mg/kg, and the remaining patients received 5 mg/kg.
Although the 24 Crohn’s disease patients followed through 14 weeks of therapy had a 42% remission rate, the remission rate jumped sharply to more than 70% among the 11 patients followed to 30 weeks.
One limitation to vedolizumab is its relatively slow onset of action, slower than anti-TNF agents, which makes vedolizumab less suitable for patients with acute, severe colitis, although short-term improvement of acute colitis can be achieved with a corticosteroid when starting a patient on vedolizumab, Dr. Singh said. A trial currently underway is collecting prospective data on vedolizumab in pediatric IBD patients that could result in pediatric labeling for the drug, she added.
Until those data are available, current experience suggests vedolizumab “is good for ulcerative colitis patients,” she said. “Our data encourage us to continue” offering vedolizumab to selected pediatric IBD patients.
Dr. Singh has been a consultant to Janssen and Prometheus and received grant support from Janssen.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Vedolizumab, 2 years out from its entry onto the U.S. market as an option for treating adults with inflammatory bowel disease, also has shown early safety and efficacy in 52 pediatric patients with ulcerative colitis or Crohn’s disease.
Retrospective review of a patients series assembled from three U.S. centers showed 13 (76%) ulcerative colitis patients in remission among 17 treated and followed for 14 weeks, the study’s primary outcome. Among 24 Crohn’s disease patients treated and followed for 14 weeks, 10 (42%) had remissions, Namita Singh, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
Treatment with vedolizumab (Entyvio), an anti-integrin with highly gut-specific activity that limits its systemic effects, was especially potent for the five patients in the series who were naive to treatment with an anti–tumor necrosis factor (TNF) agent. All five patients were in remission at 14 weeks, said Dr. Singh, a pediatric gastroenterologist at Cedars-Sinai Medical Center, Los Angeles.
“From this and other data it seems like there is a potential role for vedolizumab as first-line treatment” for selected patients, Dr. Singh said in an interview. “The attraction of vedolizumab is its gut selectivity.”
The American Gastroenterological Association lists vedolizumab as an equal alternative to an anti-TNF agent in its recommended algorithm for treating ulcerative colitis, but vedolizumab is not mentioned in the association’s posted guidance for treating Crohn’s disease. ”Prospective studies are needed” to generate more definitive evidence on how to use vedolizumab, she acknowledged, but added that pediatric gastroenterological societies “need to come up with guidelines on where to place vedolizumab.”Dr. Singh said she discusses with patients and their families the potential risks and benefits of the various treatment options available when inflammatory bowel disease (IBD) doesn’t respond to mesalamine: an anti-TNF agent, an immunomodulator like methotrexate or azathioprine, or vedolizumab. One important issue when deciding which drug class to try first is the cost of treatment and whether it will be covered by insurance.
The combined series included pediatric IBD patients less than 18 years old, with an actual median age of just under 15 years. They had been diagnosed with ulcerative colitis or Crohn’s disease for a median of 3 years. The 30 Crohn’s disease patients had received a median of two anti-TNF agents prior to starting vedolizumab, while the ulcerative colitis patients had received a median of one anti-TNF drug before vedolizumab. Three-quarters of the patients received the adult dose of 300 mg per infusion. A fifth of the patients received a dosage of 6 mg/kg, and the remaining patients received 5 mg/kg.
Although the 24 Crohn’s disease patients followed through 14 weeks of therapy had a 42% remission rate, the remission rate jumped sharply to more than 70% among the 11 patients followed to 30 weeks.
One limitation to vedolizumab is its relatively slow onset of action, slower than anti-TNF agents, which makes vedolizumab less suitable for patients with acute, severe colitis, although short-term improvement of acute colitis can be achieved with a corticosteroid when starting a patient on vedolizumab, Dr. Singh said. A trial currently underway is collecting prospective data on vedolizumab in pediatric IBD patients that could result in pediatric labeling for the drug, she added.
Until those data are available, current experience suggests vedolizumab “is good for ulcerative colitis patients,” she said. “Our data encourage us to continue” offering vedolizumab to selected pediatric IBD patients.
Dr. Singh has been a consultant to Janssen and Prometheus and received grant support from Janssen.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Fourteen weeks of treatment with vedolizumab produced remission in 76% of ulcerative colitis patients and 42% of Crohn’s disease patients.
Data source: Retrospective review of 52 pediatric patients with inflammatory bowel disease at seen at any of three U.S. centers.
Disclosures: Dr. Singh has been a consultant to Janssen and Prometheus and received grant support from Janssen.
CD64 validated as biomarker for pediatric Crohn’s disease
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.
[email protected]
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.
[email protected]
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.
[email protected]
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.
Cow’s milk allergy appears to affect more U.S. infants than thought
MONTREAL – The incidence of cow’s milk protein allergy during the first few months of life may be much more common than suggested by published studies, based on what was found is a prospective study with 700 infants seen regularly at a single, general pediatrics practice in suburban Massachusetts.
Among the 700 infants enrolled in this series, 105 (15%) were diagnosed with cow’s milk protein allergy (CMPA) when they were 5-163 days old, with a median age at diagnosis of 33 days, Victoria J. Martin, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. She and her associates confirmed that all these infants had true CMPA episodes of proctocolitis by requiring detection of blood in the stool of affected children.
The study results also suggested a protective effect against CMPA when infants received some amount of early breastfeeding, and a pilot substudy run in 47 of the enrolled infants also suggested a link between development of CMPA and abnormalities in the microbiome composition of affected infants, she reported.
While the 15% incidence rate was unexpectedly high, it “absolutely feels like what we see in routine clinical practice,” Dr. Martin said in an interview. She chalked up the much-lower figure cited in the pediatric literature as relying on strict follow-up confirmation by rechallenge of the child with cow’s milk, a step often not taken by busy clinicians. Deferring formal confirmation also often means delayed reintroduction of cow’s milk into the infant’s diet, with restriction often continuing for perhaps a year following the index episode of CMPA. Although such unnecessarily long delays in milk reintroduction have largely been considered benign, recent findings from the Learning Early About Peanut Allergy (LEAP) trial that withholding peanut exposure can increase development of peanut allergies suggests that children also might receive long-term benefit from quicker reintroduction of milk in terms of better development of the immune system and microbiome, she said.
“If we rechallenged all these infants after 1 month, I think we’d find a CMPA rate closer to 3%. Leaving infants on a mild restricted diet for 12 months is a mistake,” she added.
The Gastrointestinal Microbiome & Proctocolitis (GMAP) study enrolled 700 infants seen at a single general practice pediatric practice in suburban Massachusetts at the time of their first well-baby visit, at a median age of 8 days. During 2 years of follow-up, the researchers collected stool specimens from the enrolled children at each of up to five scheduled visits during the first 4 months. They also kept track of when children received a CMPA diagnosis confirmed by at least one bloody stool.
Analysis of CMPA correlates showed that, among infants who developed it, 17% had not received any breastfeeding soon after birth, while among infants who did not develop CMPA, 8% did not undergo early breastfeeding. The incidence of CMPA was roughly similar among infants who received an early combination of breast milk and formula and in those who received exclusively breast milk during the first days of life, showing that even partial breastfeeding is better than no breastfeeding, Dr. Martin noted.
Her analysis also includes initial results from microbial assessment of the collected serial stool specimens from a subgroup of 24 infants who developed CMPA and 23 who did not, with a total of 223 total specimens evaluated. These studies showed that the infants who developed CMPA significantly lagged in their colonization with Bifidobacteria, had significantly higher colonization levels with Enterobacteriaceae, and that in infants who did develop CMPA, their gut level of Clostridia significantly increased as their proctocolitis resolved.
Dr. Martin had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – The incidence of cow’s milk protein allergy during the first few months of life may be much more common than suggested by published studies, based on what was found is a prospective study with 700 infants seen regularly at a single, general pediatrics practice in suburban Massachusetts.
Among the 700 infants enrolled in this series, 105 (15%) were diagnosed with cow’s milk protein allergy (CMPA) when they were 5-163 days old, with a median age at diagnosis of 33 days, Victoria J. Martin, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. She and her associates confirmed that all these infants had true CMPA episodes of proctocolitis by requiring detection of blood in the stool of affected children.
The study results also suggested a protective effect against CMPA when infants received some amount of early breastfeeding, and a pilot substudy run in 47 of the enrolled infants also suggested a link between development of CMPA and abnormalities in the microbiome composition of affected infants, she reported.
While the 15% incidence rate was unexpectedly high, it “absolutely feels like what we see in routine clinical practice,” Dr. Martin said in an interview. She chalked up the much-lower figure cited in the pediatric literature as relying on strict follow-up confirmation by rechallenge of the child with cow’s milk, a step often not taken by busy clinicians. Deferring formal confirmation also often means delayed reintroduction of cow’s milk into the infant’s diet, with restriction often continuing for perhaps a year following the index episode of CMPA. Although such unnecessarily long delays in milk reintroduction have largely been considered benign, recent findings from the Learning Early About Peanut Allergy (LEAP) trial that withholding peanut exposure can increase development of peanut allergies suggests that children also might receive long-term benefit from quicker reintroduction of milk in terms of better development of the immune system and microbiome, she said.
“If we rechallenged all these infants after 1 month, I think we’d find a CMPA rate closer to 3%. Leaving infants on a mild restricted diet for 12 months is a mistake,” she added.
The Gastrointestinal Microbiome & Proctocolitis (GMAP) study enrolled 700 infants seen at a single general practice pediatric practice in suburban Massachusetts at the time of their first well-baby visit, at a median age of 8 days. During 2 years of follow-up, the researchers collected stool specimens from the enrolled children at each of up to five scheduled visits during the first 4 months. They also kept track of when children received a CMPA diagnosis confirmed by at least one bloody stool.
Analysis of CMPA correlates showed that, among infants who developed it, 17% had not received any breastfeeding soon after birth, while among infants who did not develop CMPA, 8% did not undergo early breastfeeding. The incidence of CMPA was roughly similar among infants who received an early combination of breast milk and formula and in those who received exclusively breast milk during the first days of life, showing that even partial breastfeeding is better than no breastfeeding, Dr. Martin noted.
Her analysis also includes initial results from microbial assessment of the collected serial stool specimens from a subgroup of 24 infants who developed CMPA and 23 who did not, with a total of 223 total specimens evaluated. These studies showed that the infants who developed CMPA significantly lagged in their colonization with Bifidobacteria, had significantly higher colonization levels with Enterobacteriaceae, and that in infants who did develop CMPA, their gut level of Clostridia significantly increased as their proctocolitis resolved.
Dr. Martin had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – The incidence of cow’s milk protein allergy during the first few months of life may be much more common than suggested by published studies, based on what was found is a prospective study with 700 infants seen regularly at a single, general pediatrics practice in suburban Massachusetts.
Among the 700 infants enrolled in this series, 105 (15%) were diagnosed with cow’s milk protein allergy (CMPA) when they were 5-163 days old, with a median age at diagnosis of 33 days, Victoria J. Martin, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. She and her associates confirmed that all these infants had true CMPA episodes of proctocolitis by requiring detection of blood in the stool of affected children.
The study results also suggested a protective effect against CMPA when infants received some amount of early breastfeeding, and a pilot substudy run in 47 of the enrolled infants also suggested a link between development of CMPA and abnormalities in the microbiome composition of affected infants, she reported.
While the 15% incidence rate was unexpectedly high, it “absolutely feels like what we see in routine clinical practice,” Dr. Martin said in an interview. She chalked up the much-lower figure cited in the pediatric literature as relying on strict follow-up confirmation by rechallenge of the child with cow’s milk, a step often not taken by busy clinicians. Deferring formal confirmation also often means delayed reintroduction of cow’s milk into the infant’s diet, with restriction often continuing for perhaps a year following the index episode of CMPA. Although such unnecessarily long delays in milk reintroduction have largely been considered benign, recent findings from the Learning Early About Peanut Allergy (LEAP) trial that withholding peanut exposure can increase development of peanut allergies suggests that children also might receive long-term benefit from quicker reintroduction of milk in terms of better development of the immune system and microbiome, she said.
“If we rechallenged all these infants after 1 month, I think we’d find a CMPA rate closer to 3%. Leaving infants on a mild restricted diet for 12 months is a mistake,” she added.
The Gastrointestinal Microbiome & Proctocolitis (GMAP) study enrolled 700 infants seen at a single general practice pediatric practice in suburban Massachusetts at the time of their first well-baby visit, at a median age of 8 days. During 2 years of follow-up, the researchers collected stool specimens from the enrolled children at each of up to five scheduled visits during the first 4 months. They also kept track of when children received a CMPA diagnosis confirmed by at least one bloody stool.
Analysis of CMPA correlates showed that, among infants who developed it, 17% had not received any breastfeeding soon after birth, while among infants who did not develop CMPA, 8% did not undergo early breastfeeding. The incidence of CMPA was roughly similar among infants who received an early combination of breast milk and formula and in those who received exclusively breast milk during the first days of life, showing that even partial breastfeeding is better than no breastfeeding, Dr. Martin noted.
Her analysis also includes initial results from microbial assessment of the collected serial stool specimens from a subgroup of 24 infants who developed CMPA and 23 who did not, with a total of 223 total specimens evaluated. These studies showed that the infants who developed CMPA significantly lagged in their colonization with Bifidobacteria, had significantly higher colonization levels with Enterobacteriaceae, and that in infants who did develop CMPA, their gut level of Clostridia significantly increased as their proctocolitis resolved.
Dr. Martin had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Among 700 enrolled well infants, aged 5-163 days, 105 (15%) developed proctocolitis linked with cow’s milk.
Data source: Prospective observational study of 700 healthy neonates seen at a single U.S. pediatric practice.
Disclosures: Dr. Martin had no relevant financial disclosures.
VIDEO: Harvoni shows safety, efficacy in adolescents for hepatitis C
MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.
“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.
Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.
The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.
Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.
Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.
“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.
“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.
Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.
The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.
Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.
Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.
“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.
“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.
Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.
The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.
Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.
Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.
“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Hepatitis C virus was undetectable after 12 weeks of treatment in 98%; the remaining two patients were lost to follow-up.
Data source: A multicenter, open-label study with 100 patients, aged 12-17 years old, and chronically infected with hepatitis C genotype 1.
Disclosures: The study was sponsored by Gilead, the company that markets ledipasvir/sofosbuvir (Harvoni). Dr. Murray has received research support from Gilead and is a shareholder in Merck.