Pediatrics

Two studies published in Pediatrics add new information on potential therapies as adjuncts to intravenous immunoglobulin to treat coronary artery abnormalities in pediatric Kawasaki disease patients.

Marija Stepanovic/iStock/Getty Images Plus

In the phase 3, randomized, placebo-controlled EATAK (Etanercept as Adjunctive Treatment for Acute Kawasaki Disease) trial, Michael A. Portman, MD, and his colleagues examine the effects of adding etanercept to intravenous immunoglobulin (IVIg) to study IVIg resistance in children with Kawasaki disease.

The researchers enrolled 201 participants from eight pediatric centers who received an IVIg infusion followed immediately by either subcutaneous etanercept (0.8 mg/kg; n = 100) or placebo (n = 101) and then received two more weekly doses. They performed a subgroup analysis based on age, gender, and race. The participants were between 2 months and 18 years old with incomplete (10 etanercept, 12 placebo) or complete Kawasaki disease as determined by American Heart Association criteria and American Academy of Pediatrics 2004 criteria.

Of the 35 patients who showed IVIg resistance and received a second dose, the IVIg resistance rate for participants receiving etanercept was 13%, compared with 22% in the placebo group. The overall odds ratio for IVIg resistance was 0.54. While etanercept did not lower the rate of IVIg resistance in participants younger than 1 year old, it significantly reduced IVIg resistance in those older than 1 year.

IVIg fever response significantly differed by race, which ranged from Asian participants having a 7% resistance rate to African Americans having a resistance rate of 57%.

Forty-five of all participants had greater than 2.5 baseline coronary z scores, 23 in the etanercept group and 22 in the placebo group. While etanercept reduced change in coronary z score among participants with baseline dilation (P = .04) and without baseline dilation (P = .001), there was no improvement among participants in the placebo group. Etanercept additionally reduced progression of dilation, compared with the placebo group (P = .03). The researchers noted etanercept had a good safety profile, and there were no differences between the groups receiving the intervention or placebo.

“With these considerations, EATAK results reveal a reasonable risk/benefit profile for etanercept,” Dr. Portman of Seattle Children’s Research Institute, and his colleagues concluded. “Future clinical trials, conducted in these subgroups or stratified according to patient demographics or genotypes, will be necessary to validate our findings before wide clinical adoption.”

In a second study, Audrey Dionne, MD, of Boston Children’s Hospital, and her colleagues explored how corticosteroids or infliximab together with IVIg can reduce the progression of coronary artery aneurysms (CAA). They performed a retrospective study of 121 children (73% boys; median age, 3 years) with Kawasaki disease and CAA at three different centers who received corticosteroid and IVIg therapy (n = 30), infliximab and IVIg therapy (n = 58), or IVIg alone (n = 33). The children had a coronary z score greater than or equal to 2.5 and less than 10, and there were no significant differences between median z scores among the treatment groups (P = .39).

The researchers found that patients who received corticosteroids with IVIg therapy were protected against coronary size progression (coefficient, −1.31); in addition, those patients who received infliximab and IVIg therapy were protected against coronary size progression at follow-up (coefficient, −1.07), the researchers said. Those on placebo were not.

“Our data suggest that adjunctive treatment at the time of diagnosis may be beneficial in patients with CAA,” Dr. Dionne and colleagues concluded. “Future adequately powered, prospective randomized trials are needed to determine the best adjunctive treatment of patients with KD [Kawasaki disease] who present with coronary changes.”

The EATAK trial was funded by the Food and Drug Administration Office of Orphan Product Development, Amgen, and the National Institutes of Health. Dr. Portman and colleagues reported no relevant financial disclosures. The study from Dionne et al. received funding from the McCance Family Foundation and the Vella Fund. One of the authors reported being a paid expert witness for missed diagnoses of Kawasaki disease, which was unrelated to the study. The other authors said they had no conflicts of interest.

SOURCES: Portman MA et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3675; Dionne A et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3341.

Two studies published in Pediatrics add new information on potential therapies as adjuncts to intravenous immunoglobulin to treat coronary artery abnormalities in pediatric Kawasaki disease patients.

Marija Stepanovic/iStock/Getty Images Plus

In the phase 3, randomized, placebo-controlled EATAK (Etanercept as Adjunctive Treatment for Acute Kawasaki Disease) trial, Michael A. Portman, MD, and his colleagues examine the effects of adding etanercept to intravenous immunoglobulin (IVIg) to study IVIg resistance in children with Kawasaki disease.

The researchers enrolled 201 participants from eight pediatric centers who received an IVIg infusion followed immediately by either subcutaneous etanercept (0.8 mg/kg; n = 100) or placebo (n = 101) and then received two more weekly doses. They performed a subgroup analysis based on age, gender, and race. The participants were between 2 months and 18 years old with incomplete (10 etanercept, 12 placebo) or complete Kawasaki disease as determined by American Heart Association criteria and American Academy of Pediatrics 2004 criteria.

Of the 35 patients who showed IVIg resistance and received a second dose, the IVIg resistance rate for participants receiving etanercept was 13%, compared with 22% in the placebo group. The overall odds ratio for IVIg resistance was 0.54. While etanercept did not lower the rate of IVIg resistance in participants younger than 1 year old, it significantly reduced IVIg resistance in those older than 1 year.

IVIg fever response significantly differed by race, which ranged from Asian participants having a 7% resistance rate to African Americans having a resistance rate of 57%.

Forty-five of all participants had greater than 2.5 baseline coronary z scores, 23 in the etanercept group and 22 in the placebo group. While etanercept reduced change in coronary z score among participants with baseline dilation (P = .04) and without baseline dilation (P = .001), there was no improvement among participants in the placebo group. Etanercept additionally reduced progression of dilation, compared with the placebo group (P = .03). The researchers noted etanercept had a good safety profile, and there were no differences between the groups receiving the intervention or placebo.

“With these considerations, EATAK results reveal a reasonable risk/benefit profile for etanercept,” Dr. Portman of Seattle Children’s Research Institute, and his colleagues concluded. “Future clinical trials, conducted in these subgroups or stratified according to patient demographics or genotypes, will be necessary to validate our findings before wide clinical adoption.”

In a second study, Audrey Dionne, MD, of Boston Children’s Hospital, and her colleagues explored how corticosteroids or infliximab together with IVIg can reduce the progression of coronary artery aneurysms (CAA). They performed a retrospective study of 121 children (73% boys; median age, 3 years) with Kawasaki disease and CAA at three different centers who received corticosteroid and IVIg therapy (n = 30), infliximab and IVIg therapy (n = 58), or IVIg alone (n = 33). The children had a coronary z score greater than or equal to 2.5 and less than 10, and there were no significant differences between median z scores among the treatment groups (P = .39).

The researchers found that patients who received corticosteroids with IVIg therapy were protected against coronary size progression (coefficient, −1.31); in addition, those patients who received infliximab and IVIg therapy were protected against coronary size progression at follow-up (coefficient, −1.07), the researchers said. Those on placebo were not.

“Our data suggest that adjunctive treatment at the time of diagnosis may be beneficial in patients with CAA,” Dr. Dionne and colleagues concluded. “Future adequately powered, prospective randomized trials are needed to determine the best adjunctive treatment of patients with KD [Kawasaki disease] who present with coronary changes.”

The EATAK trial was funded by the Food and Drug Administration Office of Orphan Product Development, Amgen, and the National Institutes of Health. Dr. Portman and colleagues reported no relevant financial disclosures. The study from Dionne et al. received funding from the McCance Family Foundation and the Vella Fund. One of the authors reported being a paid expert witness for missed diagnoses of Kawasaki disease, which was unrelated to the study. The other authors said they had no conflicts of interest.

SOURCES: Portman MA et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3675; Dionne A et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3341.

Two studies published in Pediatrics add new information on potential therapies as adjuncts to intravenous immunoglobulin to treat coronary artery abnormalities in pediatric Kawasaki disease patients.

Marija Stepanovic/iStock/Getty Images Plus

In the phase 3, randomized, placebo-controlled EATAK (Etanercept as Adjunctive Treatment for Acute Kawasaki Disease) trial, Michael A. Portman, MD, and his colleagues examine the effects of adding etanercept to intravenous immunoglobulin (IVIg) to study IVIg resistance in children with Kawasaki disease.

The researchers enrolled 201 participants from eight pediatric centers who received an IVIg infusion followed immediately by either subcutaneous etanercept (0.8 mg/kg; n = 100) or placebo (n = 101) and then received two more weekly doses. They performed a subgroup analysis based on age, gender, and race. The participants were between 2 months and 18 years old with incomplete (10 etanercept, 12 placebo) or complete Kawasaki disease as determined by American Heart Association criteria and American Academy of Pediatrics 2004 criteria.

Of the 35 patients who showed IVIg resistance and received a second dose, the IVIg resistance rate for participants receiving etanercept was 13%, compared with 22% in the placebo group. The overall odds ratio for IVIg resistance was 0.54. While etanercept did not lower the rate of IVIg resistance in participants younger than 1 year old, it significantly reduced IVIg resistance in those older than 1 year.

IVIg fever response significantly differed by race, which ranged from Asian participants having a 7% resistance rate to African Americans having a resistance rate of 57%.

Forty-five of all participants had greater than 2.5 baseline coronary z scores, 23 in the etanercept group and 22 in the placebo group. While etanercept reduced change in coronary z score among participants with baseline dilation (P = .04) and without baseline dilation (P = .001), there was no improvement among participants in the placebo group. Etanercept additionally reduced progression of dilation, compared with the placebo group (P = .03). The researchers noted etanercept had a good safety profile, and there were no differences between the groups receiving the intervention or placebo.

“With these considerations, EATAK results reveal a reasonable risk/benefit profile for etanercept,” Dr. Portman of Seattle Children’s Research Institute, and his colleagues concluded. “Future clinical trials, conducted in these subgroups or stratified according to patient demographics or genotypes, will be necessary to validate our findings before wide clinical adoption.”

In a second study, Audrey Dionne, MD, of Boston Children’s Hospital, and her colleagues explored how corticosteroids or infliximab together with IVIg can reduce the progression of coronary artery aneurysms (CAA). They performed a retrospective study of 121 children (73% boys; median age, 3 years) with Kawasaki disease and CAA at three different centers who received corticosteroid and IVIg therapy (n = 30), infliximab and IVIg therapy (n = 58), or IVIg alone (n = 33). The children had a coronary z score greater than or equal to 2.5 and less than 10, and there were no significant differences between median z scores among the treatment groups (P = .39).

The researchers found that patients who received corticosteroids with IVIg therapy were protected against coronary size progression (coefficient, −1.31); in addition, those patients who received infliximab and IVIg therapy were protected against coronary size progression at follow-up (coefficient, −1.07), the researchers said. Those on placebo were not.

“Our data suggest that adjunctive treatment at the time of diagnosis may be beneficial in patients with CAA,” Dr. Dionne and colleagues concluded. “Future adequately powered, prospective randomized trials are needed to determine the best adjunctive treatment of patients with KD [Kawasaki disease] who present with coronary changes.”

The EATAK trial was funded by the Food and Drug Administration Office of Orphan Product Development, Amgen, and the National Institutes of Health. Dr. Portman and colleagues reported no relevant financial disclosures. The study from Dionne et al. received funding from the McCance Family Foundation and the Vella Fund. One of the authors reported being a paid expert witness for missed diagnoses of Kawasaki disease, which was unrelated to the study. The other authors said they had no conflicts of interest.

SOURCES: Portman MA et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3675; Dionne A et al. Pediatrics. 2019. doi: 10.1542/peds.2018-3341.

How many minutes do you spend each day trying to coax new parents off the guilt train? They have delayed their childbearing until they felt comfortable economically and emotionally ready to raise a child. Convinced that up to this point they have done enough correctly to be considered successful, they see no reason that they won’t be able to tackle parenthood just as easily. Their black lab is a model of obedience. Housebreaking him was a breeze. They are skilled at using the Internet and social media to gather the information they will need for raising a child.

Jaimie Duplass/Fotolia.com

However, at some point in the first 72 hours after the birth of their child, most parents are going to hit the wall of reality. It may be that breastfeeding doesn’t work as well their cousin told them it would or simply that babies cry, often for no discernible reason. Desperately wanting to do what’s right for their child, guilt creeps in as the little failures and fatigue begin to accumulate.

In their search for answers, new parents naturally come to us as pediatricians and family practitioners for the facts, but they also will search the Internet, talk to lactation consultants, and be bombarded by unsolicited advice from family members and neighbors. Every source they turn to, including physicians, will be filtered through its own bias.

I recently came across the most sensible advice for new parents I have read in a long time, and it came not from a pediatrician but from an economics professor at Brown University. Emily Oster, PhD, writing in the New York Times, examines the available data on the topics of breastfeeding, sleep training, and parents working out of the home with the objectivity of an economist and the sensitivity of a mother who has been there and done that (“The Data All Guilt-Ridden Parents Need,” New York Times, April 19, 2019).

For example, she observes that many of the benefits of breastfeeding are supported by some evidence, “just not always especially good evidence. And even when the evidence is good, the benefits are smaller than many people realize.” She points out that “most studies of breastfeeding are biased by the fact that women who breastfeed are typically different from those who do not.” I will leave it to you to read her full discussion that includes a comparison of random trials versus observational studies. But she concludes that, if one relies on only good evidence, the only demonstrable benefit of breastfeeding is for mothers who nurse longer than 12 months who may have a 20%-30% decrease in breast cancer risk.

Using the same kind of careful analysis, Dr. Oster finds that sleep training may have a short-term benefit for parents who will have improved sleep and less maternal depression, but in the long run children who were sleep trained were no different than those that weren’t.

She also finds that, when it comes to the “optimal configuration of adult work hours” for a household, there is “no compelling evidence that proves that having a stay-at-home parent affects child outcomes, positively or negatively.” It is up to each household what works best for all it members, not just the child.

I urge you to read Dr. Oster’s article of advice on breastfeeding, sleep training or not, and working outside the home, and recommend it to struggling parents. I found it particularly helpful as a practitioner who has often felt shackled, or at least disadvantaged, by the American Academy of Pediatrics’ overly simplistic and sometimes biased recommendations on issues that send my patients’ parents on unfortunate and avoidable guilt trips.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

How many minutes do you spend each day trying to coax new parents off the guilt train? They have delayed their childbearing until they felt comfortable economically and emotionally ready to raise a child. Convinced that up to this point they have done enough correctly to be considered successful, they see no reason that they won’t be able to tackle parenthood just as easily. Their black lab is a model of obedience. Housebreaking him was a breeze. They are skilled at using the Internet and social media to gather the information they will need for raising a child.

Jaimie Duplass/Fotolia.com

However, at some point in the first 72 hours after the birth of their child, most parents are going to hit the wall of reality. It may be that breastfeeding doesn’t work as well their cousin told them it would or simply that babies cry, often for no discernible reason. Desperately wanting to do what’s right for their child, guilt creeps in as the little failures and fatigue begin to accumulate.

In their search for answers, new parents naturally come to us as pediatricians and family practitioners for the facts, but they also will search the Internet, talk to lactation consultants, and be bombarded by unsolicited advice from family members and neighbors. Every source they turn to, including physicians, will be filtered through its own bias.

I recently came across the most sensible advice for new parents I have read in a long time, and it came not from a pediatrician but from an economics professor at Brown University. Emily Oster, PhD, writing in the New York Times, examines the available data on the topics of breastfeeding, sleep training, and parents working out of the home with the objectivity of an economist and the sensitivity of a mother who has been there and done that (“The Data All Guilt-Ridden Parents Need,” New York Times, April 19, 2019).

For example, she observes that many of the benefits of breastfeeding are supported by some evidence, “just not always especially good evidence. And even when the evidence is good, the benefits are smaller than many people realize.” She points out that “most studies of breastfeeding are biased by the fact that women who breastfeed are typically different from those who do not.” I will leave it to you to read her full discussion that includes a comparison of random trials versus observational studies. But she concludes that, if one relies on only good evidence, the only demonstrable benefit of breastfeeding is for mothers who nurse longer than 12 months who may have a 20%-30% decrease in breast cancer risk.

Using the same kind of careful analysis, Dr. Oster finds that sleep training may have a short-term benefit for parents who will have improved sleep and less maternal depression, but in the long run children who were sleep trained were no different than those that weren’t.

She also finds that, when it comes to the “optimal configuration of adult work hours” for a household, there is “no compelling evidence that proves that having a stay-at-home parent affects child outcomes, positively or negatively.” It is up to each household what works best for all it members, not just the child.

I urge you to read Dr. Oster’s article of advice on breastfeeding, sleep training or not, and working outside the home, and recommend it to struggling parents. I found it particularly helpful as a practitioner who has often felt shackled, or at least disadvantaged, by the American Academy of Pediatrics’ overly simplistic and sometimes biased recommendations on issues that send my patients’ parents on unfortunate and avoidable guilt trips.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

How many minutes do you spend each day trying to coax new parents off the guilt train? They have delayed their childbearing until they felt comfortable economically and emotionally ready to raise a child. Convinced that up to this point they have done enough correctly to be considered successful, they see no reason that they won’t be able to tackle parenthood just as easily. Their black lab is a model of obedience. Housebreaking him was a breeze. They are skilled at using the Internet and social media to gather the information they will need for raising a child.

Jaimie Duplass/Fotolia.com

However, at some point in the first 72 hours after the birth of their child, most parents are going to hit the wall of reality. It may be that breastfeeding doesn’t work as well their cousin told them it would or simply that babies cry, often for no discernible reason. Desperately wanting to do what’s right for their child, guilt creeps in as the little failures and fatigue begin to accumulate.

In their search for answers, new parents naturally come to us as pediatricians and family practitioners for the facts, but they also will search the Internet, talk to lactation consultants, and be bombarded by unsolicited advice from family members and neighbors. Every source they turn to, including physicians, will be filtered through its own bias.

I recently came across the most sensible advice for new parents I have read in a long time, and it came not from a pediatrician but from an economics professor at Brown University. Emily Oster, PhD, writing in the New York Times, examines the available data on the topics of breastfeeding, sleep training, and parents working out of the home with the objectivity of an economist and the sensitivity of a mother who has been there and done that (“The Data All Guilt-Ridden Parents Need,” New York Times, April 19, 2019).

For example, she observes that many of the benefits of breastfeeding are supported by some evidence, “just not always especially good evidence. And even when the evidence is good, the benefits are smaller than many people realize.” She points out that “most studies of breastfeeding are biased by the fact that women who breastfeed are typically different from those who do not.” I will leave it to you to read her full discussion that includes a comparison of random trials versus observational studies. But she concludes that, if one relies on only good evidence, the only demonstrable benefit of breastfeeding is for mothers who nurse longer than 12 months who may have a 20%-30% decrease in breast cancer risk.

Using the same kind of careful analysis, Dr. Oster finds that sleep training may have a short-term benefit for parents who will have improved sleep and less maternal depression, but in the long run children who were sleep trained were no different than those that weren’t.

She also finds that, when it comes to the “optimal configuration of adult work hours” for a household, there is “no compelling evidence that proves that having a stay-at-home parent affects child outcomes, positively or negatively.” It is up to each household what works best for all it members, not just the child.

I urge you to read Dr. Oster’s article of advice on breastfeeding, sleep training or not, and working outside the home, and recommend it to struggling parents. I found it particularly helpful as a practitioner who has often felt shackled, or at least disadvantaged, by the American Academy of Pediatrics’ overly simplistic and sometimes biased recommendations on issues that send my patients’ parents on unfortunate and avoidable guilt trips.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

The United States put 75 new cases of measles on the board last week, bringing the total for the year to 839 as of May 10, according to the Centers for Disease Control and Prevention.

There are 10 states dealing with ongoing outbreaks now that Pennsylvania has been added to the list, the CDC reported May 13. The state has had five cases so far, all in Allegheny County. New York City continued to have the most active outbreak, adding 43 more cases in Brooklyn last week for a total of 410 in the city since the beginning of 2019, NYC Health said.

Several of this year’s outbreaks were predicted in an analysis published in the Lancet Infectious Diseases (2019 May 9. doi: 10.1016/S1473-3099(19)30231-2). Investigators identified the 25 counties most likely to experience a measles outbreak in 2019 – a list that includes Queens, N.Y. (adjacent to Brooklyn), Multnomah, Ore. (adjacent to Clark County, Wash., where 71 people were infected earlier this year), and San Mateo, Calif., where 4 cases have been reported.


“We recommend that public health officials and policymakers prioritize monitoring the counties we identify to be at high risk that have not yet reported cases, especially those that lie adjacent to counties with ongoing outbreaks and those that house large international airports,” senior author Lauren Gardner of Johns Hopkins University, Baltimore, said in a written statement.

The outbreak in Clark County was declared over in late April, but Gov. Jay Inslee signed a bill on May 10 that removes the personal/philosophical exemption for the MMR vaccine from the state’s school and child care immunization requirements. “We must step up our leadership to educate the public about the critical role vaccines have in keeping us healthy and safe, and continue working with communities to improve vaccination rates,” Washington State Secretary of Health John Wiesman said in a written statement.

In Oregon, a bill that would eliminate religious and philosophical exemptions to child vaccination requirements passed the state house of representatives by a 35-25 vote and is moving to the senate. Gov. Kate Brown has said that she plans to sign the bill, according to OregonLive.com.

The United States put 75 new cases of measles on the board last week, bringing the total for the year to 839 as of May 10, according to the Centers for Disease Control and Prevention.

There are 10 states dealing with ongoing outbreaks now that Pennsylvania has been added to the list, the CDC reported May 13. The state has had five cases so far, all in Allegheny County. New York City continued to have the most active outbreak, adding 43 more cases in Brooklyn last week for a total of 410 in the city since the beginning of 2019, NYC Health said.

Several of this year’s outbreaks were predicted in an analysis published in the Lancet Infectious Diseases (2019 May 9. doi: 10.1016/S1473-3099(19)30231-2). Investigators identified the 25 counties most likely to experience a measles outbreak in 2019 – a list that includes Queens, N.Y. (adjacent to Brooklyn), Multnomah, Ore. (adjacent to Clark County, Wash., where 71 people were infected earlier this year), and San Mateo, Calif., where 4 cases have been reported.


“We recommend that public health officials and policymakers prioritize monitoring the counties we identify to be at high risk that have not yet reported cases, especially those that lie adjacent to counties with ongoing outbreaks and those that house large international airports,” senior author Lauren Gardner of Johns Hopkins University, Baltimore, said in a written statement.

The outbreak in Clark County was declared over in late April, but Gov. Jay Inslee signed a bill on May 10 that removes the personal/philosophical exemption for the MMR vaccine from the state’s school and child care immunization requirements. “We must step up our leadership to educate the public about the critical role vaccines have in keeping us healthy and safe, and continue working with communities to improve vaccination rates,” Washington State Secretary of Health John Wiesman said in a written statement.

In Oregon, a bill that would eliminate religious and philosophical exemptions to child vaccination requirements passed the state house of representatives by a 35-25 vote and is moving to the senate. Gov. Kate Brown has said that she plans to sign the bill, according to OregonLive.com.

The United States put 75 new cases of measles on the board last week, bringing the total for the year to 839 as of May 10, according to the Centers for Disease Control and Prevention.

There are 10 states dealing with ongoing outbreaks now that Pennsylvania has been added to the list, the CDC reported May 13. The state has had five cases so far, all in Allegheny County. New York City continued to have the most active outbreak, adding 43 more cases in Brooklyn last week for a total of 410 in the city since the beginning of 2019, NYC Health said.

Several of this year’s outbreaks were predicted in an analysis published in the Lancet Infectious Diseases (2019 May 9. doi: 10.1016/S1473-3099(19)30231-2). Investigators identified the 25 counties most likely to experience a measles outbreak in 2019 – a list that includes Queens, N.Y. (adjacent to Brooklyn), Multnomah, Ore. (adjacent to Clark County, Wash., where 71 people were infected earlier this year), and San Mateo, Calif., where 4 cases have been reported.


“We recommend that public health officials and policymakers prioritize monitoring the counties we identify to be at high risk that have not yet reported cases, especially those that lie adjacent to counties with ongoing outbreaks and those that house large international airports,” senior author Lauren Gardner of Johns Hopkins University, Baltimore, said in a written statement.

The outbreak in Clark County was declared over in late April, but Gov. Jay Inslee signed a bill on May 10 that removes the personal/philosophical exemption for the MMR vaccine from the state’s school and child care immunization requirements. “We must step up our leadership to educate the public about the critical role vaccines have in keeping us healthy and safe, and continue working with communities to improve vaccination rates,” Washington State Secretary of Health John Wiesman said in a written statement.

In Oregon, a bill that would eliminate religious and philosophical exemptions to child vaccination requirements passed the state house of representatives by a 35-25 vote and is moving to the senate. Gov. Kate Brown has said that she plans to sign the bill, according to OregonLive.com.

BALTIMORE – Most pediatricians do not discuss proper tampon use and safety with their adolescent female patients, and a remarkably high proportion of them lack adequate knowledge themselves about the topic, a new survey-based study found.

Rawpixel/Thinkstock

“Significant knowledge gaps [were] noted, for instance, [such as] the maximum time a tampon can safely remain in the body,” Miriam Singer of Cohen Children’s Medical Center of New York told attendees of the Pediatric Academic Societies annual meeting.

More than 80% of females aged 17-21 years have used tampons by themselves or with pads, Ms. Singer noted in her background information, yet many teens have low knowledge about their use and safety.

Past research has found that only 35% of high school junior and senior girls heard about tampon use from their mothers, yet many of these mothers showed low knowledge about proper tampon use as well. That same research found that less than 15% of girls aged 10-19 years reported getting information from a health professional about products for menstruation despite recommendations from the American Academy of Pediatrics to instruct girls on feminine hygiene product usage.

Other research has found minimal to no education about menstruation in schools “due to time constraints and stigma associated with menstruation,” Ms. Singer said.

She and her colleagues emailed 2,500 AAP members in November-December 2018 a 53-question online questionnaire about their self-rated and measured knowledge of proper tampon usage and safety and how frequently they discussed tampons with their female adolescent patients. The survey included questions asking pediatricians to self-rate their knowledge about tampon use and safety on a Likert scale of 1 (not at all knowledgeable) to 5 (extremely knowledgeable).

Two incentives provided for completing the survey were a Feminine Hygiene Fact Sheet offered in the first email and an ADHD Medication Guide offered in the third and final email.

Among the 518 pediatricians who responded (21% response rate), 462 met the inclusion criteria of being a primary care pediatrician currently practicing in the United States. Most were women (79%) and white (79%). Just over half of the pediatricians worked only in private practice (54%) and in a suburban area (52%). About a quarter (26%) were in an urban area and 20% in a rural area. Distribution of years in practice (from 1-5 years to over 25 years in 5-year increments) was fairly even across respondents.

Only 9% of respondents reported they very often or almost always talk to their female adolescent patients about how to insert a tampon. The most common tampon-related conversation pediatricians reported was how often to change tampons, which only 35% of respondents said they very often or almost always do.

Yet a similar proportion, 36%, rarely or almost never discuss how often to change tampons, and 62% said they rarely or almost never discuss how to insert a tampon or talk about using tampons while sleeping. Half of respondents (51%) almost never discuss using tampons while swimming (only 21% very often or almost always do), and 77% have not discussed how tampons might affect the hymen with their patients.

More pediatricians (36%) reported almost never discussing the risks of tampon use with female teens than those who sometimes (32%) or very often/almost always (31%) discussed risks.

Respondents also were generally much more willing to discuss tampons with older adolescents than younger ones. Only 18% of respondents said they were highly likely to discuss them with 12- and 13-year-olds, compared with almost twice as many (33%) who would discuss tampons with 16- and 17-year-olds (P less than .001).

Male pediatricians were significantly less likely to discuss any of these topics with their female adolescent patients than female pediatricians (P less than .001 for all questions except risks [P = .01] and hymen [P = .04]). They also rated their knowledge about tampons as significantly lower than self ratings by female pediatricians (P less than .001). Less than half of pediatricians (43%) rated their knowledge about tampons as high or very high, and one in five (20%) rated it as low.

Actual measured knowledge reflected the self-ratings, but still revealed substantial gaps in knowledge among male and female providers. Just over half of male pediatricians (52%) answered all questions about tampon use and safety correctly; however, female pediatricians were only slightly better, with 71% answering all questions correctly (P less than .001). Less than half of male and female pediatricians knew the maximum time a tampon could stay in before it should be removed to reduce risk of toxic shock syndrome (8 hours).

The only two questions that more than half of male pediatricians answered correctly were that girls can swim in the ocean while wearing a tampon and that it can, rarely but not typically, tear the hymen. Less than half knew girls could sleep while wearing a tampon and that a girl could start using a tampon with her first menstruation.

More than half of female pediatricians answered all these questions correctly, although only about two-thirds gave correct answers on how tampons can affect the hymen (the only question that more male pediatricians than female answered correctly), whether a girl can sleep in a tampon, and that patients should use the lowest effective absorbency tampon to minimize toxic shock syndrome risk.

Although the study is limited by a nonvalidated knowledge assessment instrument, self-reporting and potential selection bias means the study may not accurately represent U.S. primary care pediatricians nationwide; however, the findings still demonstrate notably low self-rated and measured knowledge about tampons.

“Given the AAP’s recommendation that pediatricians instruct girls on the use of feminine products, pediatricians must take steps to ensure they are educating patients about tampons,” Ms. Singer said. She also recommended the development of web-based resources targeting the improvement of pediatrician knowledge about tampon use and safety, and the need for the AAP to raise awareness about the importance of discussing tampons with female adolescent patients.

The study did not use external funding, and the authors reported no relevant financial disclosures.

BALTIMORE – Most pediatricians do not discuss proper tampon use and safety with their adolescent female patients, and a remarkably high proportion of them lack adequate knowledge themselves about the topic, a new survey-based study found.

Rawpixel/Thinkstock

“Significant knowledge gaps [were] noted, for instance, [such as] the maximum time a tampon can safely remain in the body,” Miriam Singer of Cohen Children’s Medical Center of New York told attendees of the Pediatric Academic Societies annual meeting.

More than 80% of females aged 17-21 years have used tampons by themselves or with pads, Ms. Singer noted in her background information, yet many teens have low knowledge about their use and safety.

Past research has found that only 35% of high school junior and senior girls heard about tampon use from their mothers, yet many of these mothers showed low knowledge about proper tampon use as well. That same research found that less than 15% of girls aged 10-19 years reported getting information from a health professional about products for menstruation despite recommendations from the American Academy of Pediatrics to instruct girls on feminine hygiene product usage.

Other research has found minimal to no education about menstruation in schools “due to time constraints and stigma associated with menstruation,” Ms. Singer said.

She and her colleagues emailed 2,500 AAP members in November-December 2018 a 53-question online questionnaire about their self-rated and measured knowledge of proper tampon usage and safety and how frequently they discussed tampons with their female adolescent patients. The survey included questions asking pediatricians to self-rate their knowledge about tampon use and safety on a Likert scale of 1 (not at all knowledgeable) to 5 (extremely knowledgeable).

Two incentives provided for completing the survey were a Feminine Hygiene Fact Sheet offered in the first email and an ADHD Medication Guide offered in the third and final email.

Among the 518 pediatricians who responded (21% response rate), 462 met the inclusion criteria of being a primary care pediatrician currently practicing in the United States. Most were women (79%) and white (79%). Just over half of the pediatricians worked only in private practice (54%) and in a suburban area (52%). About a quarter (26%) were in an urban area and 20% in a rural area. Distribution of years in practice (from 1-5 years to over 25 years in 5-year increments) was fairly even across respondents.

Only 9% of respondents reported they very often or almost always talk to their female adolescent patients about how to insert a tampon. The most common tampon-related conversation pediatricians reported was how often to change tampons, which only 35% of respondents said they very often or almost always do.

Yet a similar proportion, 36%, rarely or almost never discuss how often to change tampons, and 62% said they rarely or almost never discuss how to insert a tampon or talk about using tampons while sleeping. Half of respondents (51%) almost never discuss using tampons while swimming (only 21% very often or almost always do), and 77% have not discussed how tampons might affect the hymen with their patients.

More pediatricians (36%) reported almost never discussing the risks of tampon use with female teens than those who sometimes (32%) or very often/almost always (31%) discussed risks.

Respondents also were generally much more willing to discuss tampons with older adolescents than younger ones. Only 18% of respondents said they were highly likely to discuss them with 12- and 13-year-olds, compared with almost twice as many (33%) who would discuss tampons with 16- and 17-year-olds (P less than .001).

Male pediatricians were significantly less likely to discuss any of these topics with their female adolescent patients than female pediatricians (P less than .001 for all questions except risks [P = .01] and hymen [P = .04]). They also rated their knowledge about tampons as significantly lower than self ratings by female pediatricians (P less than .001). Less than half of pediatricians (43%) rated their knowledge about tampons as high or very high, and one in five (20%) rated it as low.

Actual measured knowledge reflected the self-ratings, but still revealed substantial gaps in knowledge among male and female providers. Just over half of male pediatricians (52%) answered all questions about tampon use and safety correctly; however, female pediatricians were only slightly better, with 71% answering all questions correctly (P less than .001). Less than half of male and female pediatricians knew the maximum time a tampon could stay in before it should be removed to reduce risk of toxic shock syndrome (8 hours).

The only two questions that more than half of male pediatricians answered correctly were that girls can swim in the ocean while wearing a tampon and that it can, rarely but not typically, tear the hymen. Less than half knew girls could sleep while wearing a tampon and that a girl could start using a tampon with her first menstruation.

More than half of female pediatricians answered all these questions correctly, although only about two-thirds gave correct answers on how tampons can affect the hymen (the only question that more male pediatricians than female answered correctly), whether a girl can sleep in a tampon, and that patients should use the lowest effective absorbency tampon to minimize toxic shock syndrome risk.

Although the study is limited by a nonvalidated knowledge assessment instrument, self-reporting and potential selection bias means the study may not accurately represent U.S. primary care pediatricians nationwide; however, the findings still demonstrate notably low self-rated and measured knowledge about tampons.

“Given the AAP’s recommendation that pediatricians instruct girls on the use of feminine products, pediatricians must take steps to ensure they are educating patients about tampons,” Ms. Singer said. She also recommended the development of web-based resources targeting the improvement of pediatrician knowledge about tampon use and safety, and the need for the AAP to raise awareness about the importance of discussing tampons with female adolescent patients.

The study did not use external funding, and the authors reported no relevant financial disclosures.

BALTIMORE – Most pediatricians do not discuss proper tampon use and safety with their adolescent female patients, and a remarkably high proportion of them lack adequate knowledge themselves about the topic, a new survey-based study found.

Rawpixel/Thinkstock

“Significant knowledge gaps [were] noted, for instance, [such as] the maximum time a tampon can safely remain in the body,” Miriam Singer of Cohen Children’s Medical Center of New York told attendees of the Pediatric Academic Societies annual meeting.

More than 80% of females aged 17-21 years have used tampons by themselves or with pads, Ms. Singer noted in her background information, yet many teens have low knowledge about their use and safety.

Past research has found that only 35% of high school junior and senior girls heard about tampon use from their mothers, yet many of these mothers showed low knowledge about proper tampon use as well. That same research found that less than 15% of girls aged 10-19 years reported getting information from a health professional about products for menstruation despite recommendations from the American Academy of Pediatrics to instruct girls on feminine hygiene product usage.

Other research has found minimal to no education about menstruation in schools “due to time constraints and stigma associated with menstruation,” Ms. Singer said.

She and her colleagues emailed 2,500 AAP members in November-December 2018 a 53-question online questionnaire about their self-rated and measured knowledge of proper tampon usage and safety and how frequently they discussed tampons with their female adolescent patients. The survey included questions asking pediatricians to self-rate their knowledge about tampon use and safety on a Likert scale of 1 (not at all knowledgeable) to 5 (extremely knowledgeable).

Two incentives provided for completing the survey were a Feminine Hygiene Fact Sheet offered in the first email and an ADHD Medication Guide offered in the third and final email.

Among the 518 pediatricians who responded (21% response rate), 462 met the inclusion criteria of being a primary care pediatrician currently practicing in the United States. Most were women (79%) and white (79%). Just over half of the pediatricians worked only in private practice (54%) and in a suburban area (52%). About a quarter (26%) were in an urban area and 20% in a rural area. Distribution of years in practice (from 1-5 years to over 25 years in 5-year increments) was fairly even across respondents.

Only 9% of respondents reported they very often or almost always talk to their female adolescent patients about how to insert a tampon. The most common tampon-related conversation pediatricians reported was how often to change tampons, which only 35% of respondents said they very often or almost always do.

Yet a similar proportion, 36%, rarely or almost never discuss how often to change tampons, and 62% said they rarely or almost never discuss how to insert a tampon or talk about using tampons while sleeping. Half of respondents (51%) almost never discuss using tampons while swimming (only 21% very often or almost always do), and 77% have not discussed how tampons might affect the hymen with their patients.

More pediatricians (36%) reported almost never discussing the risks of tampon use with female teens than those who sometimes (32%) or very often/almost always (31%) discussed risks.

Respondents also were generally much more willing to discuss tampons with older adolescents than younger ones. Only 18% of respondents said they were highly likely to discuss them with 12- and 13-year-olds, compared with almost twice as many (33%) who would discuss tampons with 16- and 17-year-olds (P less than .001).

Male pediatricians were significantly less likely to discuss any of these topics with their female adolescent patients than female pediatricians (P less than .001 for all questions except risks [P = .01] and hymen [P = .04]). They also rated their knowledge about tampons as significantly lower than self ratings by female pediatricians (P less than .001). Less than half of pediatricians (43%) rated their knowledge about tampons as high or very high, and one in five (20%) rated it as low.

Actual measured knowledge reflected the self-ratings, but still revealed substantial gaps in knowledge among male and female providers. Just over half of male pediatricians (52%) answered all questions about tampon use and safety correctly; however, female pediatricians were only slightly better, with 71% answering all questions correctly (P less than .001). Less than half of male and female pediatricians knew the maximum time a tampon could stay in before it should be removed to reduce risk of toxic shock syndrome (8 hours).

The only two questions that more than half of male pediatricians answered correctly were that girls can swim in the ocean while wearing a tampon and that it can, rarely but not typically, tear the hymen. Less than half knew girls could sleep while wearing a tampon and that a girl could start using a tampon with her first menstruation.

More than half of female pediatricians answered all these questions correctly, although only about two-thirds gave correct answers on how tampons can affect the hymen (the only question that more male pediatricians than female answered correctly), whether a girl can sleep in a tampon, and that patients should use the lowest effective absorbency tampon to minimize toxic shock syndrome risk.

Although the study is limited by a nonvalidated knowledge assessment instrument, self-reporting and potential selection bias means the study may not accurately represent U.S. primary care pediatricians nationwide; however, the findings still demonstrate notably low self-rated and measured knowledge about tampons.

“Given the AAP’s recommendation that pediatricians instruct girls on the use of feminine products, pediatricians must take steps to ensure they are educating patients about tampons,” Ms. Singer said. She also recommended the development of web-based resources targeting the improvement of pediatrician knowledge about tampon use and safety, and the need for the AAP to raise awareness about the importance of discussing tampons with female adolescent patients.

The study did not use external funding, and the authors reported no relevant financial disclosures.

CHICAGO – Topical gentamicin counters the nonsense mutations that inhibit production of laminin 332 in infants with Herlitz junctional epidermolysis bullosa (H-JEB) to allow lesion healing, according to results of a small clinical study presented at the annual meeting of the Society for Investigative Dermatology.

“All of the children treated so far have responded,” reported Andrew Kwong, who will soon graduate from the Keck School of Medicine at the University of Southern California, Los Angeles.

H-JEB is an inherited blistering skin disease associated with nonsense mutations in the LAMA3, LAMB3, or LAMC2 genes that result in impaired production of functional laminin 332, an essential protein for epidermal-dermal adherence. At this time there are no effective therapies, and the disease is fatal.

The small clinical study was initiated after in vitro studies demonstrated that gentamicin restored functional laminin 332 in cultured keratinocytes from infants with H-JEB. The dose-dependent effect was credited to the ability of gentamicin to induce readthrough of premature stop codons that block production of laminin 332.

Data were presented on the first three infants with H-JEB treated with oral gentamicin. In each child, lesions were treated with topical 0.5% gentamicin twice daily for two weeks. Biopsies were taken prior to the initiation of treatment and at one and three months after treatment. The primary outcome was change in laminin 332, but clinical improvement was also monitored.

Although none of the infants had measurable laminin 332 prior to treatment, all lesions treated with topical gentamicin developed localized laminin 332 at the dermal-epidermal junction of the skin, Mr. Kwong reported. This expression, which was about 40% to 60% of that seen in normal skin, still persisted when evaluated three months after treatment.

The expression was associated with resolution of existing lesions and a reduced risk of developing new lesions, according to Mr. Kwong. In lesions that went untreated, there was no change.

Other molecular changes in the skin, such as increased expression and polarization of beta-4 integrin, were consistent with the ability of gentamicin to address the underlying pathophysiology of H-JEB. There were no adverse events observed.

By restoring functional laminin 332 in the skin, topical gentamicin appears to address the underlying cause of the bullae associated with H-JEB, but Mr. Kwong said that the next step is to determine whether intravenous gentamicin can address the systemic effects. If so, this treatment has the potential to improve survival. He reported that an infant with H-JEB was recently started on intravenous treatment, and initial results were encouraging.

Asked whether he would recommend topical gentamicin on the basis of these findings, Mr. Kwong cautioned that the case series remains very small, but he noted that the uniformity of the positive response is encouraging. He expects that off-label use of this novel and low-cost approach might be warranted in a population that has very limited therapeutic options.

SOURCE: Kwong A. SID 2019;S102, Abstract 594. Annual meeting of the Society for Investigative Dermatology.

CHICAGO – Topical gentamicin counters the nonsense mutations that inhibit production of laminin 332 in infants with Herlitz junctional epidermolysis bullosa (H-JEB) to allow lesion healing, according to results of a small clinical study presented at the annual meeting of the Society for Investigative Dermatology.

“All of the children treated so far have responded,” reported Andrew Kwong, who will soon graduate from the Keck School of Medicine at the University of Southern California, Los Angeles.

H-JEB is an inherited blistering skin disease associated with nonsense mutations in the LAMA3, LAMB3, or LAMC2 genes that result in impaired production of functional laminin 332, an essential protein for epidermal-dermal adherence. At this time there are no effective therapies, and the disease is fatal.

The small clinical study was initiated after in vitro studies demonstrated that gentamicin restored functional laminin 332 in cultured keratinocytes from infants with H-JEB. The dose-dependent effect was credited to the ability of gentamicin to induce readthrough of premature stop codons that block production of laminin 332.

Data were presented on the first three infants with H-JEB treated with oral gentamicin. In each child, lesions were treated with topical 0.5% gentamicin twice daily for two weeks. Biopsies were taken prior to the initiation of treatment and at one and three months after treatment. The primary outcome was change in laminin 332, but clinical improvement was also monitored.

Although none of the infants had measurable laminin 332 prior to treatment, all lesions treated with topical gentamicin developed localized laminin 332 at the dermal-epidermal junction of the skin, Mr. Kwong reported. This expression, which was about 40% to 60% of that seen in normal skin, still persisted when evaluated three months after treatment.

The expression was associated with resolution of existing lesions and a reduced risk of developing new lesions, according to Mr. Kwong. In lesions that went untreated, there was no change.

Other molecular changes in the skin, such as increased expression and polarization of beta-4 integrin, were consistent with the ability of gentamicin to address the underlying pathophysiology of H-JEB. There were no adverse events observed.

By restoring functional laminin 332 in the skin, topical gentamicin appears to address the underlying cause of the bullae associated with H-JEB, but Mr. Kwong said that the next step is to determine whether intravenous gentamicin can address the systemic effects. If so, this treatment has the potential to improve survival. He reported that an infant with H-JEB was recently started on intravenous treatment, and initial results were encouraging.

Asked whether he would recommend topical gentamicin on the basis of these findings, Mr. Kwong cautioned that the case series remains very small, but he noted that the uniformity of the positive response is encouraging. He expects that off-label use of this novel and low-cost approach might be warranted in a population that has very limited therapeutic options.

SOURCE: Kwong A. SID 2019;S102, Abstract 594. Annual meeting of the Society for Investigative Dermatology.

CHICAGO – Topical gentamicin counters the nonsense mutations that inhibit production of laminin 332 in infants with Herlitz junctional epidermolysis bullosa (H-JEB) to allow lesion healing, according to results of a small clinical study presented at the annual meeting of the Society for Investigative Dermatology.

“All of the children treated so far have responded,” reported Andrew Kwong, who will soon graduate from the Keck School of Medicine at the University of Southern California, Los Angeles.

H-JEB is an inherited blistering skin disease associated with nonsense mutations in the LAMA3, LAMB3, or LAMC2 genes that result in impaired production of functional laminin 332, an essential protein for epidermal-dermal adherence. At this time there are no effective therapies, and the disease is fatal.

The small clinical study was initiated after in vitro studies demonstrated that gentamicin restored functional laminin 332 in cultured keratinocytes from infants with H-JEB. The dose-dependent effect was credited to the ability of gentamicin to induce readthrough of premature stop codons that block production of laminin 332.

Data were presented on the first three infants with H-JEB treated with oral gentamicin. In each child, lesions were treated with topical 0.5% gentamicin twice daily for two weeks. Biopsies were taken prior to the initiation of treatment and at one and three months after treatment. The primary outcome was change in laminin 332, but clinical improvement was also monitored.

Although none of the infants had measurable laminin 332 prior to treatment, all lesions treated with topical gentamicin developed localized laminin 332 at the dermal-epidermal junction of the skin, Mr. Kwong reported. This expression, which was about 40% to 60% of that seen in normal skin, still persisted when evaluated three months after treatment.

The expression was associated with resolution of existing lesions and a reduced risk of developing new lesions, according to Mr. Kwong. In lesions that went untreated, there was no change.

Other molecular changes in the skin, such as increased expression and polarization of beta-4 integrin, were consistent with the ability of gentamicin to address the underlying pathophysiology of H-JEB. There were no adverse events observed.

By restoring functional laminin 332 in the skin, topical gentamicin appears to address the underlying cause of the bullae associated with H-JEB, but Mr. Kwong said that the next step is to determine whether intravenous gentamicin can address the systemic effects. If so, this treatment has the potential to improve survival. He reported that an infant with H-JEB was recently started on intravenous treatment, and initial results were encouraging.

Asked whether he would recommend topical gentamicin on the basis of these findings, Mr. Kwong cautioned that the case series remains very small, but he noted that the uniformity of the positive response is encouraging. He expects that off-label use of this novel and low-cost approach might be warranted in a population that has very limited therapeutic options.

SOURCE: Kwong A. SID 2019;S102, Abstract 594. Annual meeting of the Society for Investigative Dermatology.

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

[email protected]

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

[email protected]

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

[email protected]

BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.

Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.

“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.

Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.

The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.

The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.

Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.

To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.

Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.

Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.

These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”

Dr. Chauhan did not have any disclosures. No funding source was mentioned.

[email protected]

SOURCE: Chauhan A et al. PAS 2019. Abstract 306

BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.

Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.

“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.

Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.

The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.

The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.

Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.

To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.

Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.

Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.

These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”

Dr. Chauhan did not have any disclosures. No funding source was mentioned.

[email protected]

SOURCE: Chauhan A et al. PAS 2019. Abstract 306

BALTIMORE – Over the past 2 years, Northwell Health, a large medical system in the metropolitan New York area, increased cytomegalovirus screening for infants who fail hearing tests from 6.6% to 95% at five of its birth hospitals, according to a presentation at the Pediatric Academic Societies annual meeting.

Three cases of congenital cytomegalovirus (CMV) have been picked up so far. The plan is to roll the program out to all 10 of the system’s birth hospitals, where over 40,000 children are born each year.

“We feel very satisfied and proud” of the progress that’s been made at Northwell in such a short time, said Alia Chauhan, MD, a Northwell pediatrician who presented the findings.

Northwell launched its “Hearing Plus” program in 2017 to catch the infection before infants leave the hospital. Several other health systems around the country have launched similar programs, and a handful of states – including New York – now require CMV screening for infants who fail mandated hearing tests.

The issue is gaining traction because hearing loss is often the only sign of congenital CMV, so it’s a bellwether for infection. Screening children with hearing loss is an easy way to pick it up early, so steps can be taken to prevent problems down the road. As it is, congenital CMV is the leading nongenetic cause of hearing loss in infants, accounting for at least 10% of cases.

The Northwell program kicked off with an education campaign to build consensus among pediatricians, hospitalists, and nurses. A flyer was made about CMV screening for moms whose infants fail hearing tests, printed in both English and Spanish.

Initially, the program used urine PCR [polymerase chain reaction] to screen for CMV, but waiting for infants to produce a sample often delayed discharge, so a switch was soon made to saliva swab PCRs, which take seconds, with urine PCR held in reserve to confirm positive swabs.

To streamline the process, a standing order was added to the electronic records system so nurses could order saliva PCRs without having to get physician approval. “I think [that] was one of the biggest things that’s helped us,” Dr. Chauhan said.

Children who test positive must have urine confirmation within 21 days of birth; most are long gone from the hospital by then and have to be called back in. “We haven’t lost anyone to follow-up, but it can be stressful trying to get someone to come back,” she said.

Six of 449 infants have screened positive on saliva – three were false positives with negative urine screens. Of the three confirmed cases, two infants later turned out to have normal hearing on repeat testing and were otherwise asymptomatic.

These days, Dr. Chauhan said, if children have a positive saliva PCR but later turn out to have normal hearing, and are otherwise free of symptoms with no CMV risk factors, “we are not confirming with urine.”

Dr. Chauhan did not have any disclosures. No funding source was mentioned.

[email protected]

SOURCE: Chauhan A et al. PAS 2019. Abstract 306

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

[email protected]

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

[email protected]

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

[email protected]

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

Two new guidelines from the American College of Rheumatology provide updated recommendations for patients with juvenile idiopathic arthritis and JIA-associated uveitis while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.

The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.

“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.

These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”

“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”

As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.

Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.

Recommendations on JIA with associated uveitis

The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.

“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.

Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.

They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.

“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.

“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.

These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.

“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.

Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.

SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .

Two new guidelines from the American College of Rheumatology provide updated recommendations for patients with juvenile idiopathic arthritis and JIA-associated uveitis while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.

The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.

“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.

These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”

“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”

As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.

Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.

Recommendations on JIA with associated uveitis

The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.

“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.

Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.

They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.

“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.

“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.

These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.

“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.

Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.

SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .

Two new guidelines from the American College of Rheumatology provide updated recommendations for patients with juvenile idiopathic arthritis and JIA-associated uveitis while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.

The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.

“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.

These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”

“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”

As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.

Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.

Recommendations on JIA with associated uveitis

The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.

“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.

Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.

They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.

“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.

“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.

These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.

“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.

Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.

SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .

A Food and Drug Administration Advisory Committee voted that the benefit-risk profile of an inhaled treatment for cystic fibrosis merits approval of the drug – dry powder mannitol (DPM).

Mannitol is a naturally occurring sugar alcohol that is used as a low-calorie sweetener; it is generally recognized as safe when taken enterically. Inhaled DPM, marketed as Aridol, is currently approved as a bronchoprovocation agent. For the current indication, DPM is given as 10x40-mg capsules twice daily.

In a 9-7 vote, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) decided that DPM’s modest potential to improve pulmonary function in adults with cystic fibrosis (CF) outweighed a potential signal for increased exacerbations seen in clinical trials.

Chiesi USA Inc. is seeking approval of DPM for the management of cystic fibrosis to improve pulmonary function in patients 18 years of age and older in conjunction with standard therapies. It plans to market DPM as Bronchitol.

Some committee members who voted against approval, including PADAC chair David H. Au, MD, worried that DPM’s ease of use might prompt patients and caregivers to substitute it for inhaled hypertonic saline, a medication that’s more burdensome to use but has a longer track record for efficacy and safety. While hypertonic saline requires cumbersome equipment and cleaning regimens and takes 20-30 minutes to administer, DPM is administered over about 5 minutes via a series of capsules inserted into a small inhaler device.

“I was very impressed by conversations that we heard from the community that this will be viewed as a substitute drug [for hypertonic saline],” said Dr. Au, professor of medicine at the University of Washington, Seattle. “Before we make that leap of faith ... we have to better understand how it has to be used.” He also acknowledged that making the call for DPM was “challenging.”

Other committee members were reassured by the fact that DPM is approved for adult use in 35 countries; it’s been in use since 2011 in Australia for adults and children.

Some members also noted an unmet need in CF therapies and placed confidence in those treating CF patients to find ways to use DPM safely and effectively. “I’m really counting on the cystic fibrosis clinicians who do this for a living to figure out where to use this in their armamentarium,” said John M. Kelso, MD, an allergist at Scripps Clinic, San Diego.

In 2012, the initial new drug application submitted by Pharmaxis, which then held marketing rights to DPM, resulted in a “no” vote for approval from PADAC, and eventual FDA denial of approval. The initial submission was supported by two phase 3 clinical trials, 301 and 302, that included pediatric patients. In the pediatric population, there was concern for increased hemoptysis with DPM, so the FDA advised the drug’s marketers to consider seeking approval for an adult population only in its reapplication. The current submission followed a new double-blind, randomized, placebo-controlled trial, study 303, that included adults with CF aged 18 or over.

All three studies had similar designs, tracking change from baseline in forced expiratory volume in one second (FEV₁) from baseline to the end of the 26-week study period. In addition to this primary endpoint, secondary endpoints included other pulmonary function measures, as well as the number of protocol-defined pulmonary exacerbations (PDPEs). Participants also reported quality of life and symptom measures on the Cystic Fibrosis Questionnaire–Revised (CFQ-R).

In study 301, the dropout rate approached one in three participants with higher discontinuation in the intervention than the control arm, causing significant statistical problems in dealing with missing data. Thus, said the FDA’s Robert Lim, MD, though this study had positive results for FEV₁, it was not “statistically robust.”

The second study, 302, did not meet its primary endpoint, and there was “no support from secondary endpoints” for efficacy, said Dr. Lim, a clinical team leader in the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products.

The current submission was also supported by a new post hoc subgroup analysis of adults in studies 301 and 302. A total of 414 patients receiving DPM and 347 receiving placebo (DPM at a nontherapeutic level) were included in the integrated analysis of patients from all three studies. Studies 301 and 302 both had open-label extension arms, allowing more patients to be included in safety data.

The problems caused by the missing data from study 301 were addressed in the design of study 303 by encouraging patients who discontinued the study drug to continue data collection efforts for the study. Dropout rates were lower overall in study 303 and balanced between arms.

Over the 26-week duration of study 303, investigators saw a statistically significant improvement in FEV₁ of about 50 mL, according to the FDA’s analysis. Post hoc analyses of studies 301 and 302 showed point estimate increases of approximately 80 mL, according to Dr. Lim.

In its presentations, Chiesi USA presented its integrated analysis of adult data from the three clinical trials. The analysis showed an increase in FEV₁ from baseline of 73 mL for the DPM group, compared with an increase of 7 mL for the control group, using an intention-to-treat population (P less than .001). The committee heard evidence that in adults with CF, pulmonary function typically decreases by 1%-3% annually.

The PDPE rate was slightly higher in the DPM group than in the control group in studies 302 and 303, but the differences were not statistically significant. These findings have a backdrop of an overall low rate of PDPEs ranging from 0.221 to 0.995 per year, according to Chiesi presenter Scott Donaldson, MD, a pulmonologist who directs the adult cystic fibrosis center at the University of North Carolina at Chapel Hill.

When looking at the subgroup of United States study participants, the DPM integrated cohort included more patients with a history of prior pulmonary exacerbations. In the DPM group, 45% of U.S. participants had at least one exacerbation in the prior year, and 20% had two or more exacerbations, compared with 38% and 14%, respectively, in the control group. Chiesi argued that this imbalance was likely responsible for the increased exacerbation rate.

The sponsor and the FDA used different imputation methods to account for missing data from the earlier studies, complicating interpretation of the potential signal for increased exacerbations.

Quality of life data were similar between groups across the studies.

In the end, the view of the “yes” voters was encapsulated by James M. Tracy, DO, an allergist in private practice in Omaha, Neb. “This is not a drug for everybody; but absolutely, it’s a drug for somebody. Ultimately we have to make that decision – I do think that we study populations, but we really take care of people.”

The FDA usually follows the recommendations of its advisory panels.

[email protected]

A Food and Drug Administration Advisory Committee voted that the benefit-risk profile of an inhaled treatment for cystic fibrosis merits approval of the drug – dry powder mannitol (DPM).

Mannitol is a naturally occurring sugar alcohol that is used as a low-calorie sweetener; it is generally recognized as safe when taken enterically. Inhaled DPM, marketed as Aridol, is currently approved as a bronchoprovocation agent. For the current indication, DPM is given as 10x40-mg capsules twice daily.

In a 9-7 vote, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) decided that DPM’s modest potential to improve pulmonary function in adults with cystic fibrosis (CF) outweighed a potential signal for increased exacerbations seen in clinical trials.

Chiesi USA Inc. is seeking approval of DPM for the management of cystic fibrosis to improve pulmonary function in patients 18 years of age and older in conjunction with standard therapies. It plans to market DPM as Bronchitol.

Some committee members who voted against approval, including PADAC chair David H. Au, MD, worried that DPM’s ease of use might prompt patients and caregivers to substitute it for inhaled hypertonic saline, a medication that’s more burdensome to use but has a longer track record for efficacy and safety. While hypertonic saline requires cumbersome equipment and cleaning regimens and takes 20-30 minutes to administer, DPM is administered over about 5 minutes via a series of capsules inserted into a small inhaler device.

“I was very impressed by conversations that we heard from the community that this will be viewed as a substitute drug [for hypertonic saline],” said Dr. Au, professor of medicine at the University of Washington, Seattle. “Before we make that leap of faith ... we have to better understand how it has to be used.” He also acknowledged that making the call for DPM was “challenging.”

Other committee members were reassured by the fact that DPM is approved for adult use in 35 countries; it’s been in use since 2011 in Australia for adults and children.

Some members also noted an unmet need in CF therapies and placed confidence in those treating CF patients to find ways to use DPM safely and effectively. “I’m really counting on the cystic fibrosis clinicians who do this for a living to figure out where to use this in their armamentarium,” said John M. Kelso, MD, an allergist at Scripps Clinic, San Diego.

In 2012, the initial new drug application submitted by Pharmaxis, which then held marketing rights to DPM, resulted in a “no” vote for approval from PADAC, and eventual FDA denial of approval. The initial submission was supported by two phase 3 clinical trials, 301 and 302, that included pediatric patients. In the pediatric population, there was concern for increased hemoptysis with DPM, so the FDA advised the drug’s marketers to consider seeking approval for an adult population only in its reapplication. The current submission followed a new double-blind, randomized, placebo-controlled trial, study 303, that included adults with CF aged 18 or over.

All three studies had similar designs, tracking change from baseline in forced expiratory volume in one second (FEV₁) from baseline to the end of the 26-week study period. In addition to this primary endpoint, secondary endpoints included other pulmonary function measures, as well as the number of protocol-defined pulmonary exacerbations (PDPEs). Participants also reported quality of life and symptom measures on the Cystic Fibrosis Questionnaire–Revised (CFQ-R).

In study 301, the dropout rate approached one in three participants with higher discontinuation in the intervention than the control arm, causing significant statistical problems in dealing with missing data. Thus, said the FDA’s Robert Lim, MD, though this study had positive results for FEV₁, it was not “statistically robust.”

The second study, 302, did not meet its primary endpoint, and there was “no support from secondary endpoints” for efficacy, said Dr. Lim, a clinical team leader in the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products.

The current submission was also supported by a new post hoc subgroup analysis of adults in studies 301 and 302. A total of 414 patients receiving DPM and 347 receiving placebo (DPM at a nontherapeutic level) were included in the integrated analysis of patients from all three studies. Studies 301 and 302 both had open-label extension arms, allowing more patients to be included in safety data.

The problems caused by the missing data from study 301 were addressed in the design of study 303 by encouraging patients who discontinued the study drug to continue data collection efforts for the study. Dropout rates were lower overall in study 303 and balanced between arms.

Over the 26-week duration of study 303, investigators saw a statistically significant improvement in FEV₁ of about 50 mL, according to the FDA’s analysis. Post hoc analyses of studies 301 and 302 showed point estimate increases of approximately 80 mL, according to Dr. Lim.

In its presentations, Chiesi USA presented its integrated analysis of adult data from the three clinical trials. The analysis showed an increase in FEV₁ from baseline of 73 mL for the DPM group, compared with an increase of 7 mL for the control group, using an intention-to-treat population (P less than .001). The committee heard evidence that in adults with CF, pulmonary function typically decreases by 1%-3% annually.

The PDPE rate was slightly higher in the DPM group than in the control group in studies 302 and 303, but the differences were not statistically significant. These findings have a backdrop of an overall low rate of PDPEs ranging from 0.221 to 0.995 per year, according to Chiesi presenter Scott Donaldson, MD, a pulmonologist who directs the adult cystic fibrosis center at the University of North Carolina at Chapel Hill.

When looking at the subgroup of United States study participants, the DPM integrated cohort included more patients with a history of prior pulmonary exacerbations. In the DPM group, 45% of U.S. participants had at least one exacerbation in the prior year, and 20% had two or more exacerbations, compared with 38% and 14%, respectively, in the control group. Chiesi argued that this imbalance was likely responsible for the increased exacerbation rate.

The sponsor and the FDA used different imputation methods to account for missing data from the earlier studies, complicating interpretation of the potential signal for increased exacerbations.

Quality of life data were similar between groups across the studies.

In the end, the view of the “yes” voters was encapsulated by James M. Tracy, DO, an allergist in private practice in Omaha, Neb. “This is not a drug for everybody; but absolutely, it’s a drug for somebody. Ultimately we have to make that decision – I do think that we study populations, but we really take care of people.”

The FDA usually follows the recommendations of its advisory panels.

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A Food and Drug Administration Advisory Committee voted that the benefit-risk profile of an inhaled treatment for cystic fibrosis merits approval of the drug – dry powder mannitol (DPM).

Mannitol is a naturally occurring sugar alcohol that is used as a low-calorie sweetener; it is generally recognized as safe when taken enterically. Inhaled DPM, marketed as Aridol, is currently approved as a bronchoprovocation agent. For the current indication, DPM is given as 10x40-mg capsules twice daily.

In a 9-7 vote, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) decided that DPM’s modest potential to improve pulmonary function in adults with cystic fibrosis (CF) outweighed a potential signal for increased exacerbations seen in clinical trials.

Chiesi USA Inc. is seeking approval of DPM for the management of cystic fibrosis to improve pulmonary function in patients 18 years of age and older in conjunction with standard therapies. It plans to market DPM as Bronchitol.

Some committee members who voted against approval, including PADAC chair David H. Au, MD, worried that DPM’s ease of use might prompt patients and caregivers to substitute it for inhaled hypertonic saline, a medication that’s more burdensome to use but has a longer track record for efficacy and safety. While hypertonic saline requires cumbersome equipment and cleaning regimens and takes 20-30 minutes to administer, DPM is administered over about 5 minutes via a series of capsules inserted into a small inhaler device.

“I was very impressed by conversations that we heard from the community that this will be viewed as a substitute drug [for hypertonic saline],” said Dr. Au, professor of medicine at the University of Washington, Seattle. “Before we make that leap of faith ... we have to better understand how it has to be used.” He also acknowledged that making the call for DPM was “challenging.”

Other committee members were reassured by the fact that DPM is approved for adult use in 35 countries; it’s been in use since 2011 in Australia for adults and children.

Some members also noted an unmet need in CF therapies and placed confidence in those treating CF patients to find ways to use DPM safely and effectively. “I’m really counting on the cystic fibrosis clinicians who do this for a living to figure out where to use this in their armamentarium,” said John M. Kelso, MD, an allergist at Scripps Clinic, San Diego.

In 2012, the initial new drug application submitted by Pharmaxis, which then held marketing rights to DPM, resulted in a “no” vote for approval from PADAC, and eventual FDA denial of approval. The initial submission was supported by two phase 3 clinical trials, 301 and 302, that included pediatric patients. In the pediatric population, there was concern for increased hemoptysis with DPM, so the FDA advised the drug’s marketers to consider seeking approval for an adult population only in its reapplication. The current submission followed a new double-blind, randomized, placebo-controlled trial, study 303, that included adults with CF aged 18 or over.

All three studies had similar designs, tracking change from baseline in forced expiratory volume in one second (FEV₁) from baseline to the end of the 26-week study period. In addition to this primary endpoint, secondary endpoints included other pulmonary function measures, as well as the number of protocol-defined pulmonary exacerbations (PDPEs). Participants also reported quality of life and symptom measures on the Cystic Fibrosis Questionnaire–Revised (CFQ-R).

In study 301, the dropout rate approached one in three participants with higher discontinuation in the intervention than the control arm, causing significant statistical problems in dealing with missing data. Thus, said the FDA’s Robert Lim, MD, though this study had positive results for FEV₁, it was not “statistically robust.”

The second study, 302, did not meet its primary endpoint, and there was “no support from secondary endpoints” for efficacy, said Dr. Lim, a clinical team leader in the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products.

The current submission was also supported by a new post hoc subgroup analysis of adults in studies 301 and 302. A total of 414 patients receiving DPM and 347 receiving placebo (DPM at a nontherapeutic level) were included in the integrated analysis of patients from all three studies. Studies 301 and 302 both had open-label extension arms, allowing more patients to be included in safety data.

The problems caused by the missing data from study 301 were addressed in the design of study 303 by encouraging patients who discontinued the study drug to continue data collection efforts for the study. Dropout rates were lower overall in study 303 and balanced between arms.

Over the 26-week duration of study 303, investigators saw a statistically significant improvement in FEV₁ of about 50 mL, according to the FDA’s analysis. Post hoc analyses of studies 301 and 302 showed point estimate increases of approximately 80 mL, according to Dr. Lim.

In its presentations, Chiesi USA presented its integrated analysis of adult data from the three clinical trials. The analysis showed an increase in FEV₁ from baseline of 73 mL for the DPM group, compared with an increase of 7 mL for the control group, using an intention-to-treat population (P less than .001). The committee heard evidence that in adults with CF, pulmonary function typically decreases by 1%-3% annually.

The PDPE rate was slightly higher in the DPM group than in the control group in studies 302 and 303, but the differences were not statistically significant. These findings have a backdrop of an overall low rate of PDPEs ranging from 0.221 to 0.995 per year, according to Chiesi presenter Scott Donaldson, MD, a pulmonologist who directs the adult cystic fibrosis center at the University of North Carolina at Chapel Hill.

When looking at the subgroup of United States study participants, the DPM integrated cohort included more patients with a history of prior pulmonary exacerbations. In the DPM group, 45% of U.S. participants had at least one exacerbation in the prior year, and 20% had two or more exacerbations, compared with 38% and 14%, respectively, in the control group. Chiesi argued that this imbalance was likely responsible for the increased exacerbation rate.

The sponsor and the FDA used different imputation methods to account for missing data from the earlier studies, complicating interpretation of the potential signal for increased exacerbations.

Quality of life data were similar between groups across the studies.

In the end, the view of the “yes” voters was encapsulated by James M. Tracy, DO, an allergist in private practice in Omaha, Neb. “This is not a drug for everybody; but absolutely, it’s a drug for somebody. Ultimately we have to make that decision – I do think that we study populations, but we really take care of people.”

The FDA usually follows the recommendations of its advisory panels.

[email protected]