Heidi Splete

The use of compounded bioidentical hormone therapies should be limited to patients who are not able to use a hormone therapy product approved by the Food and Drug Administration for reasons of allergy or dosage, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

yacobchuk/Getty Images

In recent years, compounded bioidentical hormone therapies (cBHTs) have been “marketed as a personalized and natural approach to enhanced wellness using tailored preparations that address a myriad of symptoms, including those associated with menopause and aging,” wrote Donald R. Mattison, MD, of the University of Ottawa, and chair of the committee charged with producing the report, and colleagues.

Although both cBHTs and bioidentical hormone therapies (BHTs) contain hormones that are structurally and chemically identical to those in the human body, cBHTs have not undergone the safety, efficacy, and quality control tests of approved FDA products, according to the report.

In addition, cBHTs have no standardization when it comes to medication doses, and the products often are available in topicals such as creams or ointments, as well as pills or pellets. The lack of standards in dosing or form can contribute to the risk of overdose, the report emphasized.

Various cBTH products continue to be marketed to the public for age-related hormone symptoms including hot flashes associated with menopause and decreased muscle mass associated with decreased testosterone. However, cBHTs are not approved by the FDA in part because the individually mixed products are not tested to verify the amount of hormone that may be absorbed.

In response to the increased use of cBHTs, the National Academies convened a Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy and commissioned a report.

The two typical reasons to prescribe cBHT are either to provide a medication in an alternate dose not available in approved products or to omit components of a medication to which a patient is allergic, according to the report.

The report includes an algorithm to help guide clinicians in prescribing FDA-approved products, including off-label use of approved products, before cBHT products. “There is a dearth of high-quality evidence ... available to establish whether cBHT preparations are safe or efficacious for their prescribed uses,” the report states.

Of note, the committee also found no guidelines to recommend the use of cBHT products as a substitute for off-label use of FDA-approved BHT products for patients with female sexual dysfunction or gender dysphoria, two conditions for which no FDA-approved BHT products exist.

“The North American Menopause Society applauds the efforts of the National Academies of Sciences, Engineering, and Medicine (NASEM) and endorses their recommendations on compounded bioidentical hormone therapy,” Stephanie S. Faubion, MD, medical director of The North American Menopause Society, wrote in a statement. “As a society, we remain committed to improving the care of midlife women through the promotion of evidence-based research, education, and clinical care.”

A report on the use of cBHTs was important at this time because of the widespread and largely unregulated use of these products with little data to support their safety and efficacy, Dr. Faubion said in an interview.

“There are no indications for use of custom compounded hormone therapy aside from an allergy to a component in the FDA-approved products or lack of availability of the needed dose, which would be exceedingly rare given the variety of forms and doses available with FDA-approved products,” she said.

Main concerns regarding the use of cBHTs are the lack of safety and efficacy data, Dr. Faubion emphasized. “Women believe these products are safer than FDA-approved products because they do not receive a package insert outlining potential risks as they do with FDA-approved products.” A lack of data and safety monitoring of cBHTs means that adverse effects are not monitored and reported, she said. Also, safety concerns persist regarding some forms of cBHTs such as pellets, which were specifically highlighted in the report.

Dr. Faubion said that she “absolutely” agrees with the report’s limited circumstances in which the used of cBHTs would be appropriate. “There are very few reasons why women would need to use compounded hormones instead of the FDA-approved versions, which are regulated for quality, efficacy and safety, readily available in the local pharmacy, and often covered by insurance.”

In terms of the future, “we need more education for women as consumers and for medical providers on this topic,” Dr. Faubion noted. Also, “clearly, there is a dearth of research on the true efficacy and safety of these compounded hormone therapy products.”

The statement from the National Academies crystallizes what experts have been saying for decades, according to Lubna Pal, MBBS, director of the menopause program at Yale University, New Haven, Conn.

The formal recommendations to limit the use of cBHTs “are not novel, but certainly needed,” and the statement “offers guidance regardless of your specialty,” Dr. Pal said in an interview.

There is often a disconnect between consumers’ understanding of compounding and the reality of safety concerns, she said. “We are in a tabloid era,” and education is key to guiding patients toward the FDA-approved treatments with safety data and demonstrated effectiveness, she said. “Safety should be the driving factor.” In compounded products, “there is no consistency that what you get today is the same as what you get tomorrow,” and the lack of standardization of cBHTs increases the risk for adverse events, she emphasized.

For patients with special needs such as allergies or other specialized dosing requirements, as noted in the National Academies statement, clinicians should discuss the options with patients and monitor them regularly to head off potential adverse events such as the development of uterine cancer, said Dr. Pal, who is a member of the Ob.Gyn. News editorial advisory board.

The research involved in creating the report was supported by the Food and Drug Administration.

Dr. Faubion had no financial conflicts to disclose. Dr. Pal had no relevant financial disclosures.

obnews@mdedge.com

SOURCE: Mattison DR et al.; National Academies of Sciences, Engineering, and Medicine. The clinical utility of compounded bioidentical hormone therapy: A review of safety, effectiveness, and use. (Washington, DC: The National Academies Press. 2020.)

The use of compounded bioidentical hormone therapies should be limited to patients who are not able to use a hormone therapy product approved by the Food and Drug Administration for reasons of allergy or dosage, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

yacobchuk/Getty Images

In recent years, compounded bioidentical hormone therapies (cBHTs) have been “marketed as a personalized and natural approach to enhanced wellness using tailored preparations that address a myriad of symptoms, including those associated with menopause and aging,” wrote Donald R. Mattison, MD, of the University of Ottawa, and chair of the committee charged with producing the report, and colleagues.

Although both cBHTs and bioidentical hormone therapies (BHTs) contain hormones that are structurally and chemically identical to those in the human body, cBHTs have not undergone the safety, efficacy, and quality control tests of approved FDA products, according to the report.

In addition, cBHTs have no standardization when it comes to medication doses, and the products often are available in topicals such as creams or ointments, as well as pills or pellets. The lack of standards in dosing or form can contribute to the risk of overdose, the report emphasized.

Various cBTH products continue to be marketed to the public for age-related hormone symptoms including hot flashes associated with menopause and decreased muscle mass associated with decreased testosterone. However, cBHTs are not approved by the FDA in part because the individually mixed products are not tested to verify the amount of hormone that may be absorbed.

In response to the increased use of cBHTs, the National Academies convened a Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy and commissioned a report.

The two typical reasons to prescribe cBHT are either to provide a medication in an alternate dose not available in approved products or to omit components of a medication to which a patient is allergic, according to the report.

The report includes an algorithm to help guide clinicians in prescribing FDA-approved products, including off-label use of approved products, before cBHT products. “There is a dearth of high-quality evidence ... available to establish whether cBHT preparations are safe or efficacious for their prescribed uses,” the report states.

Of note, the committee also found no guidelines to recommend the use of cBHT products as a substitute for off-label use of FDA-approved BHT products for patients with female sexual dysfunction or gender dysphoria, two conditions for which no FDA-approved BHT products exist.

“The North American Menopause Society applauds the efforts of the National Academies of Sciences, Engineering, and Medicine (NASEM) and endorses their recommendations on compounded bioidentical hormone therapy,” Stephanie S. Faubion, MD, medical director of The North American Menopause Society, wrote in a statement. “As a society, we remain committed to improving the care of midlife women through the promotion of evidence-based research, education, and clinical care.”

A report on the use of cBHTs was important at this time because of the widespread and largely unregulated use of these products with little data to support their safety and efficacy, Dr. Faubion said in an interview.

“There are no indications for use of custom compounded hormone therapy aside from an allergy to a component in the FDA-approved products or lack of availability of the needed dose, which would be exceedingly rare given the variety of forms and doses available with FDA-approved products,” she said.

Main concerns regarding the use of cBHTs are the lack of safety and efficacy data, Dr. Faubion emphasized. “Women believe these products are safer than FDA-approved products because they do not receive a package insert outlining potential risks as they do with FDA-approved products.” A lack of data and safety monitoring of cBHTs means that adverse effects are not monitored and reported, she said. Also, safety concerns persist regarding some forms of cBHTs such as pellets, which were specifically highlighted in the report.

Dr. Faubion said that she “absolutely” agrees with the report’s limited circumstances in which the used of cBHTs would be appropriate. “There are very few reasons why women would need to use compounded hormones instead of the FDA-approved versions, which are regulated for quality, efficacy and safety, readily available in the local pharmacy, and often covered by insurance.”

In terms of the future, “we need more education for women as consumers and for medical providers on this topic,” Dr. Faubion noted. Also, “clearly, there is a dearth of research on the true efficacy and safety of these compounded hormone therapy products.”

The statement from the National Academies crystallizes what experts have been saying for decades, according to Lubna Pal, MBBS, director of the menopause program at Yale University, New Haven, Conn.

The formal recommendations to limit the use of cBHTs “are not novel, but certainly needed,” and the statement “offers guidance regardless of your specialty,” Dr. Pal said in an interview.

There is often a disconnect between consumers’ understanding of compounding and the reality of safety concerns, she said. “We are in a tabloid era,” and education is key to guiding patients toward the FDA-approved treatments with safety data and demonstrated effectiveness, she said. “Safety should be the driving factor.” In compounded products, “there is no consistency that what you get today is the same as what you get tomorrow,” and the lack of standardization of cBHTs increases the risk for adverse events, she emphasized.

For patients with special needs such as allergies or other specialized dosing requirements, as noted in the National Academies statement, clinicians should discuss the options with patients and monitor them regularly to head off potential adverse events such as the development of uterine cancer, said Dr. Pal, who is a member of the Ob.Gyn. News editorial advisory board.

The research involved in creating the report was supported by the Food and Drug Administration.

Dr. Faubion had no financial conflicts to disclose. Dr. Pal had no relevant financial disclosures.

obnews@mdedge.com

SOURCE: Mattison DR et al.; National Academies of Sciences, Engineering, and Medicine. The clinical utility of compounded bioidentical hormone therapy: A review of safety, effectiveness, and use. (Washington, DC: The National Academies Press. 2020.)

The use of compounded bioidentical hormone therapies should be limited to patients who are not able to use a hormone therapy product approved by the Food and Drug Administration for reasons of allergy or dosage, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

yacobchuk/Getty Images

In recent years, compounded bioidentical hormone therapies (cBHTs) have been “marketed as a personalized and natural approach to enhanced wellness using tailored preparations that address a myriad of symptoms, including those associated with menopause and aging,” wrote Donald R. Mattison, MD, of the University of Ottawa, and chair of the committee charged with producing the report, and colleagues.

Although both cBHTs and bioidentical hormone therapies (BHTs) contain hormones that are structurally and chemically identical to those in the human body, cBHTs have not undergone the safety, efficacy, and quality control tests of approved FDA products, according to the report.

In addition, cBHTs have no standardization when it comes to medication doses, and the products often are available in topicals such as creams or ointments, as well as pills or pellets. The lack of standards in dosing or form can contribute to the risk of overdose, the report emphasized.

Various cBTH products continue to be marketed to the public for age-related hormone symptoms including hot flashes associated with menopause and decreased muscle mass associated with decreased testosterone. However, cBHTs are not approved by the FDA in part because the individually mixed products are not tested to verify the amount of hormone that may be absorbed.

In response to the increased use of cBHTs, the National Academies convened a Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy and commissioned a report.

The two typical reasons to prescribe cBHT are either to provide a medication in an alternate dose not available in approved products or to omit components of a medication to which a patient is allergic, according to the report.

The report includes an algorithm to help guide clinicians in prescribing FDA-approved products, including off-label use of approved products, before cBHT products. “There is a dearth of high-quality evidence ... available to establish whether cBHT preparations are safe or efficacious for their prescribed uses,” the report states.

Of note, the committee also found no guidelines to recommend the use of cBHT products as a substitute for off-label use of FDA-approved BHT products for patients with female sexual dysfunction or gender dysphoria, two conditions for which no FDA-approved BHT products exist.

“The North American Menopause Society applauds the efforts of the National Academies of Sciences, Engineering, and Medicine (NASEM) and endorses their recommendations on compounded bioidentical hormone therapy,” Stephanie S. Faubion, MD, medical director of The North American Menopause Society, wrote in a statement. “As a society, we remain committed to improving the care of midlife women through the promotion of evidence-based research, education, and clinical care.”

A report on the use of cBHTs was important at this time because of the widespread and largely unregulated use of these products with little data to support their safety and efficacy, Dr. Faubion said in an interview.

“There are no indications for use of custom compounded hormone therapy aside from an allergy to a component in the FDA-approved products or lack of availability of the needed dose, which would be exceedingly rare given the variety of forms and doses available with FDA-approved products,” she said.

Main concerns regarding the use of cBHTs are the lack of safety and efficacy data, Dr. Faubion emphasized. “Women believe these products are safer than FDA-approved products because they do not receive a package insert outlining potential risks as they do with FDA-approved products.” A lack of data and safety monitoring of cBHTs means that adverse effects are not monitored and reported, she said. Also, safety concerns persist regarding some forms of cBHTs such as pellets, which were specifically highlighted in the report.

Dr. Faubion said that she “absolutely” agrees with the report’s limited circumstances in which the used of cBHTs would be appropriate. “There are very few reasons why women would need to use compounded hormones instead of the FDA-approved versions, which are regulated for quality, efficacy and safety, readily available in the local pharmacy, and often covered by insurance.”

In terms of the future, “we need more education for women as consumers and for medical providers on this topic,” Dr. Faubion noted. Also, “clearly, there is a dearth of research on the true efficacy and safety of these compounded hormone therapy products.”

The statement from the National Academies crystallizes what experts have been saying for decades, according to Lubna Pal, MBBS, director of the menopause program at Yale University, New Haven, Conn.

The formal recommendations to limit the use of cBHTs “are not novel, but certainly needed,” and the statement “offers guidance regardless of your specialty,” Dr. Pal said in an interview.

There is often a disconnect between consumers’ understanding of compounding and the reality of safety concerns, she said. “We are in a tabloid era,” and education is key to guiding patients toward the FDA-approved treatments with safety data and demonstrated effectiveness, she said. “Safety should be the driving factor.” In compounded products, “there is no consistency that what you get today is the same as what you get tomorrow,” and the lack of standardization of cBHTs increases the risk for adverse events, she emphasized.

For patients with special needs such as allergies or other specialized dosing requirements, as noted in the National Academies statement, clinicians should discuss the options with patients and monitor them regularly to head off potential adverse events such as the development of uterine cancer, said Dr. Pal, who is a member of the Ob.Gyn. News editorial advisory board.

The research involved in creating the report was supported by the Food and Drug Administration.

Dr. Faubion had no financial conflicts to disclose. Dr. Pal had no relevant financial disclosures.

obnews@mdedge.com

SOURCE: Mattison DR et al.; National Academies of Sciences, Engineering, and Medicine. The clinical utility of compounded bioidentical hormone therapy: A review of safety, effectiveness, and use. (Washington, DC: The National Academies Press. 2020.)

Physicians have been slow to embrace biosimilar versions of infliximab, but are more likely to prescribe it to new patients, based on data from a review of nearly 50,000 infliximab claims through Medicare in the first 2 years that biosimilars were available in the United States.

“Although biosimilar versions are as safe and effective as the biologic, patients and physicians may be more reluctant to switch from a working biologic regimen in a chronic setting than an acute one,” wrote Alice J. Chen, PhD, of the University of Southern California, Los Angeles, and colleagues.

In a research letter published in JAMA Internal Medicine, the investigators examined prescribing patterns of physicians switching between the originator infliximab (Remicade) and two of its biosimilars (Inflectra and Renflexis).

They reviewed infliximab use and reimbursement in the 100% Medicare Part B quarterly claims database from Jan. 1, 2017, to Dec. 31, 2018. The study population included Medicare patients classified as new if they had no infliximab claims in the prior 6 months; those with claims were considered returning patients.

In a comparison of claims reflecting 49,771 patients and 4,289 physicians in 2018, a total of 1,418 new patients (17.4%) and 4,495 (10.8%) returning patients used a biosimilar. “Of returning patients, half used the biosimilar version exclusively, whereas the other half switched between biologic and biosimilar versions,” the researchers noted.

Of the 4,289 physicians who prescribed infliximab, 3,124 prescribed no biosimilars, 1,015 prescribed both biologics and biosimilars, and 150 prescribed biosimilars only. Of the physicians who prescribed both, approximately 61% switched some patients from the biologic to the biosimilar; “the remainder kept individual patients on only 1 version of the drug but treated patients with both versions,” the researchers wrote.

The adoption of biosimilars may be slower for chronic vs. acute conditions, the researchers noted. “Prescribers may hesitate to switch clinically stable chronic patients from biologic regimens if they are unfamiliar with the biosimilar or face financial disincentives from prescribing it.”

The study findings were limited by several factors including the use of only 2 years of data and a focus only on Medicare Part B. Switching medications may have been influenced by factors such as lower copays for patients and rebates or discounts for physicians; however, “further research is needed to better understand biosimilar pricing dynamics and the barriers to adopting biosimilars for chronic conditions,” they concluded.

The study was supported by the Leonard D. Schaeffer Center for Health Policy & Economics at the University of Southern California, Los Angeles, and the National Institute on Aging. Lead author Dr. Chen also disclosed receiving personal fees from Amgen outside of the current study.

SOURCE: Chen AJ et al. JAMA Intern Med. 2020 July 20. doi: 10.1001/jamainternmed.2020.3188.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at www.gastro.org/biosimilars.

Physicians have been slow to embrace biosimilar versions of infliximab, but are more likely to prescribe it to new patients, based on data from a review of nearly 50,000 infliximab claims through Medicare in the first 2 years that biosimilars were available in the United States.

“Although biosimilar versions are as safe and effective as the biologic, patients and physicians may be more reluctant to switch from a working biologic regimen in a chronic setting than an acute one,” wrote Alice J. Chen, PhD, of the University of Southern California, Los Angeles, and colleagues.

In a research letter published in JAMA Internal Medicine, the investigators examined prescribing patterns of physicians switching between the originator infliximab (Remicade) and two of its biosimilars (Inflectra and Renflexis).

They reviewed infliximab use and reimbursement in the 100% Medicare Part B quarterly claims database from Jan. 1, 2017, to Dec. 31, 2018. The study population included Medicare patients classified as new if they had no infliximab claims in the prior 6 months; those with claims were considered returning patients.

In a comparison of claims reflecting 49,771 patients and 4,289 physicians in 2018, a total of 1,418 new patients (17.4%) and 4,495 (10.8%) returning patients used a biosimilar. “Of returning patients, half used the biosimilar version exclusively, whereas the other half switched between biologic and biosimilar versions,” the researchers noted.

Of the 4,289 physicians who prescribed infliximab, 3,124 prescribed no biosimilars, 1,015 prescribed both biologics and biosimilars, and 150 prescribed biosimilars only. Of the physicians who prescribed both, approximately 61% switched some patients from the biologic to the biosimilar; “the remainder kept individual patients on only 1 version of the drug but treated patients with both versions,” the researchers wrote.

The adoption of biosimilars may be slower for chronic vs. acute conditions, the researchers noted. “Prescribers may hesitate to switch clinically stable chronic patients from biologic regimens if they are unfamiliar with the biosimilar or face financial disincentives from prescribing it.”

The study findings were limited by several factors including the use of only 2 years of data and a focus only on Medicare Part B. Switching medications may have been influenced by factors such as lower copays for patients and rebates or discounts for physicians; however, “further research is needed to better understand biosimilar pricing dynamics and the barriers to adopting biosimilars for chronic conditions,” they concluded.

The study was supported by the Leonard D. Schaeffer Center for Health Policy & Economics at the University of Southern California, Los Angeles, and the National Institute on Aging. Lead author Dr. Chen also disclosed receiving personal fees from Amgen outside of the current study.

SOURCE: Chen AJ et al. JAMA Intern Med. 2020 July 20. doi: 10.1001/jamainternmed.2020.3188.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at www.gastro.org/biosimilars.

Physicians have been slow to embrace biosimilar versions of infliximab, but are more likely to prescribe it to new patients, based on data from a review of nearly 50,000 infliximab claims through Medicare in the first 2 years that biosimilars were available in the United States.

“Although biosimilar versions are as safe and effective as the biologic, patients and physicians may be more reluctant to switch from a working biologic regimen in a chronic setting than an acute one,” wrote Alice J. Chen, PhD, of the University of Southern California, Los Angeles, and colleagues.

In a research letter published in JAMA Internal Medicine, the investigators examined prescribing patterns of physicians switching between the originator infliximab (Remicade) and two of its biosimilars (Inflectra and Renflexis).

They reviewed infliximab use and reimbursement in the 100% Medicare Part B quarterly claims database from Jan. 1, 2017, to Dec. 31, 2018. The study population included Medicare patients classified as new if they had no infliximab claims in the prior 6 months; those with claims were considered returning patients.

In a comparison of claims reflecting 49,771 patients and 4,289 physicians in 2018, a total of 1,418 new patients (17.4%) and 4,495 (10.8%) returning patients used a biosimilar. “Of returning patients, half used the biosimilar version exclusively, whereas the other half switched between biologic and biosimilar versions,” the researchers noted.

Of the 4,289 physicians who prescribed infliximab, 3,124 prescribed no biosimilars, 1,015 prescribed both biologics and biosimilars, and 150 prescribed biosimilars only. Of the physicians who prescribed both, approximately 61% switched some patients from the biologic to the biosimilar; “the remainder kept individual patients on only 1 version of the drug but treated patients with both versions,” the researchers wrote.

The adoption of biosimilars may be slower for chronic vs. acute conditions, the researchers noted. “Prescribers may hesitate to switch clinically stable chronic patients from biologic regimens if they are unfamiliar with the biosimilar or face financial disincentives from prescribing it.”

The study findings were limited by several factors including the use of only 2 years of data and a focus only on Medicare Part B. Switching medications may have been influenced by factors such as lower copays for patients and rebates or discounts for physicians; however, “further research is needed to better understand biosimilar pricing dynamics and the barriers to adopting biosimilars for chronic conditions,” they concluded.

The study was supported by the Leonard D. Schaeffer Center for Health Policy & Economics at the University of Southern California, Los Angeles, and the National Institute on Aging. Lead author Dr. Chen also disclosed receiving personal fees from Amgen outside of the current study.

SOURCE: Chen AJ et al. JAMA Intern Med. 2020 July 20. doi: 10.1001/jamainternmed.2020.3188.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at www.gastro.org/biosimilars.

Physicians have been slow to embrace biosimilar versions of infliximab, but are more likely to prescribe it to new patients, based on data from a review of nearly 50,000 infliximab claims through Medicare in the first 2 years that biosimilars were available in the United States.

“Although biosimilar versions are as safe and effective as the biologic, patients and physicians may be more reluctant to switch from a working biologic regimen in a chronic setting than an acute one,” wrote Alice J. Chen, PhD, of the University of Southern California, Los Angeles, and colleagues.

In a research letter published in JAMA Internal Medicine, the investigators examined prescribing patterns of physicians switching between the originator infliximab (Remicade) and two of its biosimilars (Inflectra and Renflexis).

They reviewed infliximab use and reimbursement in the 100% Medicare Part B quarterly claims database from Jan. 1, 2017, to Dec. 31, 2018. The study population included Medicare patients classified as new if they had no infliximab claims in the prior 6 months; those with claims were considered returning patients.

In a comparison of claims reflecting 49,771 patients and 4,289 physicians in 2018, a total of 1,418 new patients (17.4%) and 4,495 (10.8%) returning patients used a biosimilar. “Of returning patients, half used the biosimilar version exclusively, whereas the other half switched between biologic and biosimilar versions,” the researchers noted.

Of the 4,289 physicians who prescribed infliximab, 3,124 prescribed no biosimilars, 1,015 prescribed both biologics and biosimilars, and 150 prescribed biosimilars only. Of the physicians who prescribed both, approximately 61% switched some patients from the biologic to the biosimilar; “the remainder kept individual patients on only 1 version of the drug but treated patients with both versions,” the researchers wrote.

The adoption of biosimilars may be slower for chronic vs. acute conditions, the researchers noted. “Prescribers may hesitate to switch clinically stable chronic patients from biologic regimens if they are unfamiliar with the biosimilar or face financial disincentives from prescribing it.”

The study findings were limited by several factors including the use of only 2 years of data and a focus only on Medicare Part B. Switching medications may have been influenced by factors such as lower copays for patients and rebates or discounts for physicians; however, “further research is needed to better understand biosimilar pricing dynamics and the barriers to adopting biosimilars for chronic conditions,” they concluded.

The study was supported by the Leonard D. Schaeffer Center for Health Policy & Economics at the University of Southern California, Los Angeles, and the National Institute on Aging. Lead author Dr. Chen also disclosed receiving personal fees from Amgen outside of the current study.

SOURCE: Chen AJ et al. JAMA Intern Med. 2020 July 20. doi: 10.1001/jamainternmed.2020.3188.

Physicians have been slow to embrace biosimilar versions of infliximab, but are more likely to prescribe it to new patients, based on data from a review of nearly 50,000 infliximab claims through Medicare in the first 2 years that biosimilars were available in the United States.

“Although biosimilar versions are as safe and effective as the biologic, patients and physicians may be more reluctant to switch from a working biologic regimen in a chronic setting than an acute one,” wrote Alice J. Chen, PhD, of the University of Southern California, Los Angeles, and colleagues.

In a research letter published in JAMA Internal Medicine, the investigators examined prescribing patterns of physicians switching between the originator infliximab (Remicade) and two of its biosimilars (Inflectra and Renflexis).

They reviewed infliximab use and reimbursement in the 100% Medicare Part B quarterly claims database from Jan. 1, 2017, to Dec. 31, 2018. The study population included Medicare patients classified as new if they had no infliximab claims in the prior 6 months; those with claims were considered returning patients.

In a comparison of claims reflecting 49,771 patients and 4,289 physicians in 2018, a total of 1,418 new patients (17.4%) and 4,495 (10.8%) returning patients used a biosimilar. “Of returning patients, half used the biosimilar version exclusively, whereas the other half switched between biologic and biosimilar versions,” the researchers noted.

Of the 4,289 physicians who prescribed infliximab, 3,124 prescribed no biosimilars, 1,015 prescribed both biologics and biosimilars, and 150 prescribed biosimilars only. Of the physicians who prescribed both, approximately 61% switched some patients from the biologic to the biosimilar; “the remainder kept individual patients on only 1 version of the drug but treated patients with both versions,” the researchers wrote.

The adoption of biosimilars may be slower for chronic vs. acute conditions, the researchers noted. “Prescribers may hesitate to switch clinically stable chronic patients from biologic regimens if they are unfamiliar with the biosimilar or face financial disincentives from prescribing it.”

The study findings were limited by several factors including the use of only 2 years of data and a focus only on Medicare Part B. Switching medications may have been influenced by factors such as lower copays for patients and rebates or discounts for physicians; however, “further research is needed to better understand biosimilar pricing dynamics and the barriers to adopting biosimilars for chronic conditions,” they concluded.

The study was supported by the Leonard D. Schaeffer Center for Health Policy & Economics at the University of Southern California, Los Angeles, and the National Institute on Aging. Lead author Dr. Chen also disclosed receiving personal fees from Amgen outside of the current study.

SOURCE: Chen AJ et al. JAMA Intern Med. 2020 July 20. doi: 10.1001/jamainternmed.2020.3188.

Physicians have been slow to embrace biosimilar versions of infliximab, but are more likely to prescribe it to new patients, based on data from a review of nearly 50,000 infliximab claims through Medicare in the first 2 years that biosimilars were available in the United States.

“Although biosimilar versions are as safe and effective as the biologic, patients and physicians may be more reluctant to switch from a working biologic regimen in a chronic setting than an acute one,” wrote Alice J. Chen, PhD, of the University of Southern California, Los Angeles, and colleagues.

In a research letter published in JAMA Internal Medicine, the investigators examined prescribing patterns of physicians switching between the originator infliximab (Remicade) and two of its biosimilars (Inflectra and Renflexis).

They reviewed infliximab use and reimbursement in the 100% Medicare Part B quarterly claims database from Jan. 1, 2017, to Dec. 31, 2018. The study population included Medicare patients classified as new if they had no infliximab claims in the prior 6 months; those with claims were considered returning patients.

In a comparison of claims reflecting 49,771 patients and 4,289 physicians in 2018, a total of 1,418 new patients (17.4%) and 4,495 (10.8%) returning patients used a biosimilar. “Of returning patients, half used the biosimilar version exclusively, whereas the other half switched between biologic and biosimilar versions,” the researchers noted.

Of the 4,289 physicians who prescribed infliximab, 3,124 prescribed no biosimilars, 1,015 prescribed both biologics and biosimilars, and 150 prescribed biosimilars only. Of the physicians who prescribed both, approximately 61% switched some patients from the biologic to the biosimilar; “the remainder kept individual patients on only 1 version of the drug but treated patients with both versions,” the researchers wrote.

The adoption of biosimilars may be slower for chronic vs. acute conditions, the researchers noted. “Prescribers may hesitate to switch clinically stable chronic patients from biologic regimens if they are unfamiliar with the biosimilar or face financial disincentives from prescribing it.”

The study findings were limited by several factors including the use of only 2 years of data and a focus only on Medicare Part B. Switching medications may have been influenced by factors such as lower copays for patients and rebates or discounts for physicians; however, “further research is needed to better understand biosimilar pricing dynamics and the barriers to adopting biosimilars for chronic conditions,” they concluded.

The study was supported by the Leonard D. Schaeffer Center for Health Policy & Economics at the University of Southern California, Los Angeles, and the National Institute on Aging. Lead author Dr. Chen also disclosed receiving personal fees from Amgen outside of the current study.

SOURCE: Chen AJ et al. JAMA Intern Med. 2020 July 20. doi: 10.1001/jamainternmed.2020.3188.

The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.

However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.

In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.

Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.

Dr. Nuzzo suggested that schools should prioritize students who will benefit most from in-person learning, such as younger children and those with special needs. Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.

None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”

At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.

Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:

• Core academics
• SARS-CoV-2 protection
• Before and after school programs
• School access and transportation
• Student health services
• Food and nutrition.

Ethics/equity categories include the following:

• Parent choice
• Teacher and staff choice
• Children of poverty and systemic disadvantage
• Children with special needs/English as second language/gifted and twice exceptional
• Privacy
• Engagement and transparency.

As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.

School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.

Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.

In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.

The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.

The briefing participants had no relevant financial conflicts to disclose.

The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.

However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.

In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.

Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.

Dr. Nuzzo suggested that schools should prioritize students who will benefit most from in-person learning, such as younger children and those with special needs. Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.

None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”

At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.

Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:

• Core academics
• SARS-CoV-2 protection
• Before and after school programs
• School access and transportation
• Student health services
• Food and nutrition.

Ethics/equity categories include the following:

• Parent choice
• Teacher and staff choice
• Children of poverty and systemic disadvantage
• Children with special needs/English as second language/gifted and twice exceptional
• Privacy
• Engagement and transparency.

As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.

School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.

Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.

In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.

The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.

The briefing participants had no relevant financial conflicts to disclose.

The absence of in-person school has harmed children in ways beyond loss of academic learning, according to Josh Sharfstein, MD, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health, Baltimore. In addition to learning, school is a place where many children receive breakfast and lunch every day, as well as support services and the benefits of being in a safe and secure environment, Dr. Sharfstein said in a press briefing sponsored by Johns Hopkins University.

However, although it is an important priority for children to return to school, “we are in the midst of a pandemic that poses real risk,” he said.

In the press briefing, several experts shared ideas and considerations for safely reopening K-12 schools in the fall of 2020.

Data from other countries where schools have reopened, notably Austria and Denmark, have been reassuring about the lack of transmission of SARS-CoV-2 among children in a school setting, said Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins Center for Health Security. However, other countries where schools have reopened successfully have reported low levels of viral transmission locally, and a responsible strategy for school reopening in the United States should follow a similar plan, she said. In areas where transmission and infection rates are increasing “it may not be safe to reopen,” but in areas where rates are declining or stable, schools could potentially reopen if they follow safety measures.

Dr. Nuzzo suggested that schools should prioritize students who will benefit most from in-person learning, such as younger children and those with special needs. Considerations include protocols for handwashing and sanitation, and maintaining physical distance by creative use of outdoor classrooms (weather permitting) or other spaces within school buildings. Transportation to and from school also will be an issue to address, she noted.

None of the strategies being considered will completely eliminate risk of SARS-CoV-2 infection in school settings, so allowing parents and students to opt out and choose distance learning will be important as well, said Dr. Nuzzo. In addition, schools may need to consider alternative roles for teachers and staff who don’t feel comfortable being in contact with students and fellow staff members. “All of these things are going to be hard,” Dr. Nuzzo acknowledged. “Hard should not be a deterrent,” to reopening schools, but “we acknowledge the resources that schools will need in order to do this.”

At present, all 50 states and the District of Columbia have released some type of plan for reopening schools, said Megan Collins, MD, MPH, codirector the Johns Hopkins Consortium for School-Based Health Solutions.

Dr. Collins and colleagues have developed a school reopening tracker, which is “a national snapshot of current reopening plans that have been released,” she said. The tracker is being updated continuously as plans evolve. The eSchool+ K-12 School Reopening Tracker identifies 12 reopening categories that states could potentially address in the plans. These categories are divided into Operational and Ethics/Equity. The operational categories include:

• Core academics
• SARS-CoV-2 protection
• Before and after school programs
• School access and transportation
• Student health services
• Food and nutrition.

Ethics/equity categories include the following:

• Parent choice
• Teacher and staff choice
• Children of poverty and systemic disadvantage
• Children with special needs/English as second language/gifted and twice exceptional
• Privacy
• Engagement and transparency.

As of July 15, 2020, 16 states (Arizona, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, North Carolina, North Dakota, Ohio, Rhode Island, Tennessee, Texas, Virginia, Washington, and Wisconsin) had addressed all 12 categories in their reopening plans, Dr. Collins said.

School reopening plans must take equity issues into account, said Annette Anderson, PhD, of the Johns Hopkins University School of Education.

Specifically, developing learning plans for special education students and others at the most risk for learning loss will be essential. “The digital divide has become a digital canyon” in some areas, Dr. Anderson noted, and schools need to rethink eligibility and work to provide access to devices for online learning for all students.

In addition, schools need to convince parents that schools are safe. She recommended that schools consider inviting parents and families to visit buildings in advance of reopening so they can see the safety measures, such as space between desks, cleaning stations, and other protective strategies.

The message to pediatricians and health care professionals when counseling families about returning individual children to school is to consider the risk to the child and the family directly in the context of the local plans, Dr. Sharfstein said during a question and answer session. “One school system’s plan is one school system’s plan,” he said, and added that families who are concerned about the risk should have an online option. However, “if you see a thoughtful approach” to reopening, with safety steps taken and parents informed, with protocols such as keeping small groups of children together to reduce transmission, “it is a pretty good trade-off,” and that is why the American Academy of Pediatrics currently favors children returning to school, he said.

The briefing participants had no relevant financial conflicts to disclose.

A trio of international expert recommendations mainly agree on essentials for the diagnosis and treatment of polycystic ovary syndrome in adolescents, but some confusion persists, according to Robert L. Rosenfield, MD, of the University of California, San Francisco.

In a commentary published in the Journal of Pediatric & Adolescent Gynecology, Dr. Rosenfield, who convened one of the three conferences at which guidance was developed, noted that the three recommendations – published by the Pediatric Endocrine Society, the International Consortium of Paediatric Endocrinology, and the International PCOS Network in 2015, 2017, and 2018, respectively – “are fairly dense” and reviews have suggested a lack of agreement. His comments offer perspective and practice suggestions that follow the consensus of the recommendations.

“All the documents agree on the core diagnostic criteria for adolescent PCOS: otherwise unexplained evidence of ovulatory dysfunction, as indicated by menstrual abnormalities based on stage-appropriate standards, and evidence of an androgen excess disorder,” Dr. Rosenfield said.

The main differences among the recommendations from the three groups reflect tension between the value of an early diagnosis and the liabilities of a mistaken diagnosis in the context of attitudes about adolescent contraception. “These are issues not likely to be resolved easily, yet they are matters for every physician to consider in management of each case,” he said.

Dr. Rosenfield emphasized that clinicians must consider PCOS “in the general context of all causes of adolescent menstrual disturbances,” when evaluating a girl within 1-2 years of menarche who presents with a menstrual abnormality, hirsutism, and/or acne that has been resistant to topical treatment.

A key point on which the recommendations differ is whether further assessment is needed if the menstrual abnormality has persisted for 1 year (the 2018 recommendations) or 2 years (the 2015 and 2017 recommendations), Dr. Rosenfield explained. “What the conferees struggled with is differentiating how long after menarche a menstrual abnormality should persist to avoid confusing PCOS with normal immaturity of the menstrual cycle,” known as physiologic adolescent anovulation (PAA). “The degree of certainty is improved only modestly by waiting 2 years rather than 1 year to make a diagnosis.”

However, the three documents agree that girls suspected of having PCOS within the first 1-2 years after menarche should be evaluated at that time, and followed with a diagnosis of “at risk for PCOS” if the early test results are consistent with a PCOS diagnosis, he said.

Another point of difference among the groups is the extent to which hirsutism and acne represent clinical evidence of hyperandrogenism that justifies testing for biochemical hyperandrogenism, Dr. Rosenfield said.

“All three sets of adolescent PCOS recommendations agree that investigation for biochemical hyperandrogenism be initiated by measuring serum total and/or free testosterone by specialty assays with well-defined reference ranges,” he said.

However, “documentation of biochemical hyperandrogenism has been problematic because standard platform assays of testosterone give grossly inaccurate results.”

As for the management of PCOS in teens, “different perspectives about pharmacologic treatment [reflect] the multicultural views about adolescent contraception,” said Dr. Rosenfield. Guidelines in the United States favor estrogen-progestin combined oral contraceptives as first-line therapy, while the international guidelines support contraceptives if contraception also is desired; otherwise the 2017 guidelines recommend metformin as a first-line treatment.

“Agreement is uniform that healthy lifestyle management is first-line therapy for management of the associated obesity and metabolic disturbances, i.e., prior to and/or in conjunction with metformin therapy,” he noted.

In general, Dr. Rosenfield acknowledged that front-line clinicians cannot easily evaluate all early postmenarcheal girls for abnormal menstrual cycles. Instead, he advocated a “middle ground” approach between early diagnosis and potentially labeling a girl with a false positive diagnosis.

Postmenarcheal girls who are amenorrheic for 2 months could be assessed for signs of PCOS or pregnancy, and whether she is generally in good health, he said. “However, for example, if she remains amenorrheic for more than 90 days or if two successive periods are more than 2 months apart, laboratory screening would be reasonable.”

PCOS is “a diagnosis of exclusion for which referral to a specialist is advisable” to rule out other conditions such as non-classic congenital adrenal hyperplasia, hyperprolactinemia, endogenous Cushing syndrome, thyroid dysfunction, and virilizing tumors, said Dr. Rosenfield.

However, PCOS accounts for most cases of adolescent hyperandrogenism. The symptomatic treatment of early postmenarcheal girls at risk of PCOS is recommended to manage menstrual abnormality, hirsutism, acne, or obesity, and these girls should be reassessed by the time they finish high school after a 3-month treatment withdrawal period, he emphasized.

Dr. Rosenfield had no relevant financial conflicts to disclose.

SOURCE: Rosenfield RL. J Pediatr Adolesc Gynecol. 2020 June 29. doi: 10.1016/j.jpag.2020.06.017.

A trio of international expert recommendations mainly agree on essentials for the diagnosis and treatment of polycystic ovary syndrome in adolescents, but some confusion persists, according to Robert L. Rosenfield, MD, of the University of California, San Francisco.

In a commentary published in the Journal of Pediatric & Adolescent Gynecology, Dr. Rosenfield, who convened one of the three conferences at which guidance was developed, noted that the three recommendations – published by the Pediatric Endocrine Society, the International Consortium of Paediatric Endocrinology, and the International PCOS Network in 2015, 2017, and 2018, respectively – “are fairly dense” and reviews have suggested a lack of agreement. His comments offer perspective and practice suggestions that follow the consensus of the recommendations.

“All the documents agree on the core diagnostic criteria for adolescent PCOS: otherwise unexplained evidence of ovulatory dysfunction, as indicated by menstrual abnormalities based on stage-appropriate standards, and evidence of an androgen excess disorder,” Dr. Rosenfield said.

The main differences among the recommendations from the three groups reflect tension between the value of an early diagnosis and the liabilities of a mistaken diagnosis in the context of attitudes about adolescent contraception. “These are issues not likely to be resolved easily, yet they are matters for every physician to consider in management of each case,” he said.

Dr. Rosenfield emphasized that clinicians must consider PCOS “in the general context of all causes of adolescent menstrual disturbances,” when evaluating a girl within 1-2 years of menarche who presents with a menstrual abnormality, hirsutism, and/or acne that has been resistant to topical treatment.

A key point on which the recommendations differ is whether further assessment is needed if the menstrual abnormality has persisted for 1 year (the 2018 recommendations) or 2 years (the 2015 and 2017 recommendations), Dr. Rosenfield explained. “What the conferees struggled with is differentiating how long after menarche a menstrual abnormality should persist to avoid confusing PCOS with normal immaturity of the menstrual cycle,” known as physiologic adolescent anovulation (PAA). “The degree of certainty is improved only modestly by waiting 2 years rather than 1 year to make a diagnosis.”

However, the three documents agree that girls suspected of having PCOS within the first 1-2 years after menarche should be evaluated at that time, and followed with a diagnosis of “at risk for PCOS” if the early test results are consistent with a PCOS diagnosis, he said.

Another point of difference among the groups is the extent to which hirsutism and acne represent clinical evidence of hyperandrogenism that justifies testing for biochemical hyperandrogenism, Dr. Rosenfield said.

“All three sets of adolescent PCOS recommendations agree that investigation for biochemical hyperandrogenism be initiated by measuring serum total and/or free testosterone by specialty assays with well-defined reference ranges,” he said.

However, “documentation of biochemical hyperandrogenism has been problematic because standard platform assays of testosterone give grossly inaccurate results.”

As for the management of PCOS in teens, “different perspectives about pharmacologic treatment [reflect] the multicultural views about adolescent contraception,” said Dr. Rosenfield. Guidelines in the United States favor estrogen-progestin combined oral contraceptives as first-line therapy, while the international guidelines support contraceptives if contraception also is desired; otherwise the 2017 guidelines recommend metformin as a first-line treatment.

“Agreement is uniform that healthy lifestyle management is first-line therapy for management of the associated obesity and metabolic disturbances, i.e., prior to and/or in conjunction with metformin therapy,” he noted.

In general, Dr. Rosenfield acknowledged that front-line clinicians cannot easily evaluate all early postmenarcheal girls for abnormal menstrual cycles. Instead, he advocated a “middle ground” approach between early diagnosis and potentially labeling a girl with a false positive diagnosis.

Postmenarcheal girls who are amenorrheic for 2 months could be assessed for signs of PCOS or pregnancy, and whether she is generally in good health, he said. “However, for example, if she remains amenorrheic for more than 90 days or if two successive periods are more than 2 months apart, laboratory screening would be reasonable.”

PCOS is “a diagnosis of exclusion for which referral to a specialist is advisable” to rule out other conditions such as non-classic congenital adrenal hyperplasia, hyperprolactinemia, endogenous Cushing syndrome, thyroid dysfunction, and virilizing tumors, said Dr. Rosenfield.

However, PCOS accounts for most cases of adolescent hyperandrogenism. The symptomatic treatment of early postmenarcheal girls at risk of PCOS is recommended to manage menstrual abnormality, hirsutism, acne, or obesity, and these girls should be reassessed by the time they finish high school after a 3-month treatment withdrawal period, he emphasized.

Dr. Rosenfield had no relevant financial conflicts to disclose.

SOURCE: Rosenfield RL. J Pediatr Adolesc Gynecol. 2020 June 29. doi: 10.1016/j.jpag.2020.06.017.

A trio of international expert recommendations mainly agree on essentials for the diagnosis and treatment of polycystic ovary syndrome in adolescents, but some confusion persists, according to Robert L. Rosenfield, MD, of the University of California, San Francisco.

In a commentary published in the Journal of Pediatric & Adolescent Gynecology, Dr. Rosenfield, who convened one of the three conferences at which guidance was developed, noted that the three recommendations – published by the Pediatric Endocrine Society, the International Consortium of Paediatric Endocrinology, and the International PCOS Network in 2015, 2017, and 2018, respectively – “are fairly dense” and reviews have suggested a lack of agreement. His comments offer perspective and practice suggestions that follow the consensus of the recommendations.

“All the documents agree on the core diagnostic criteria for adolescent PCOS: otherwise unexplained evidence of ovulatory dysfunction, as indicated by menstrual abnormalities based on stage-appropriate standards, and evidence of an androgen excess disorder,” Dr. Rosenfield said.

The main differences among the recommendations from the three groups reflect tension between the value of an early diagnosis and the liabilities of a mistaken diagnosis in the context of attitudes about adolescent contraception. “These are issues not likely to be resolved easily, yet they are matters for every physician to consider in management of each case,” he said.

Dr. Rosenfield emphasized that clinicians must consider PCOS “in the general context of all causes of adolescent menstrual disturbances,” when evaluating a girl within 1-2 years of menarche who presents with a menstrual abnormality, hirsutism, and/or acne that has been resistant to topical treatment.

A key point on which the recommendations differ is whether further assessment is needed if the menstrual abnormality has persisted for 1 year (the 2018 recommendations) or 2 years (the 2015 and 2017 recommendations), Dr. Rosenfield explained. “What the conferees struggled with is differentiating how long after menarche a menstrual abnormality should persist to avoid confusing PCOS with normal immaturity of the menstrual cycle,” known as physiologic adolescent anovulation (PAA). “The degree of certainty is improved only modestly by waiting 2 years rather than 1 year to make a diagnosis.”

However, the three documents agree that girls suspected of having PCOS within the first 1-2 years after menarche should be evaluated at that time, and followed with a diagnosis of “at risk for PCOS” if the early test results are consistent with a PCOS diagnosis, he said.

Another point of difference among the groups is the extent to which hirsutism and acne represent clinical evidence of hyperandrogenism that justifies testing for biochemical hyperandrogenism, Dr. Rosenfield said.

“All three sets of adolescent PCOS recommendations agree that investigation for biochemical hyperandrogenism be initiated by measuring serum total and/or free testosterone by specialty assays with well-defined reference ranges,” he said.

However, “documentation of biochemical hyperandrogenism has been problematic because standard platform assays of testosterone give grossly inaccurate results.”

As for the management of PCOS in teens, “different perspectives about pharmacologic treatment [reflect] the multicultural views about adolescent contraception,” said Dr. Rosenfield. Guidelines in the United States favor estrogen-progestin combined oral contraceptives as first-line therapy, while the international guidelines support contraceptives if contraception also is desired; otherwise the 2017 guidelines recommend metformin as a first-line treatment.

“Agreement is uniform that healthy lifestyle management is first-line therapy for management of the associated obesity and metabolic disturbances, i.e., prior to and/or in conjunction with metformin therapy,” he noted.

In general, Dr. Rosenfield acknowledged that front-line clinicians cannot easily evaluate all early postmenarcheal girls for abnormal menstrual cycles. Instead, he advocated a “middle ground” approach between early diagnosis and potentially labeling a girl with a false positive diagnosis.

Postmenarcheal girls who are amenorrheic for 2 months could be assessed for signs of PCOS or pregnancy, and whether she is generally in good health, he said. “However, for example, if she remains amenorrheic for more than 90 days or if two successive periods are more than 2 months apart, laboratory screening would be reasonable.”

PCOS is “a diagnosis of exclusion for which referral to a specialist is advisable” to rule out other conditions such as non-classic congenital adrenal hyperplasia, hyperprolactinemia, endogenous Cushing syndrome, thyroid dysfunction, and virilizing tumors, said Dr. Rosenfield.

However, PCOS accounts for most cases of adolescent hyperandrogenism. The symptomatic treatment of early postmenarcheal girls at risk of PCOS is recommended to manage menstrual abnormality, hirsutism, acne, or obesity, and these girls should be reassessed by the time they finish high school after a 3-month treatment withdrawal period, he emphasized.

Dr. Rosenfield had no relevant financial conflicts to disclose.

SOURCE: Rosenfield RL. J Pediatr Adolesc Gynecol. 2020 June 29. doi: 10.1016/j.jpag.2020.06.017.

Women have a lower risk of nonalcoholic fatty liver disease compared with men, but those who do develop the disease are significantly more likely than are men to develop advanced fibrosis, according to data from a meta-analysis of more than 62,000 individuals.

Sex disparity persists in most chronic liver diseases, with more cases and risk of progression reported in men, but the effect of sex on nonalcoholic fatty liver disease (NAFLD) remains unclear, wrote Maya Balakrishnan, MD, of Baylor College of Medicine, Houston, and colleagues. “Knowing whether and how [sex] influences the risk and severity of NAFLD is important for risk stratification, risk modification as well as prognostication,” they said.

In a study published in Clinical Gastroenterology and Hepatology, the researchers conducted a review and meta-analysis of 54 studies, including data from 62,239 patients with NAFLD, 5,428 with nonalcoholic steatohepatitis (NASH), and 6,444 with advanced NAFLD fibrosis.

Overall, women had a 19% lower risk of developing NAFLD compared with men (pooled risk ratio 0.81), a similar risk to men of developing NASH (RR, 1.00), and a 37% increased risk of advanced fibrosis (RR, 1.37) compared with men.

The risk of more severe disease in women increased with age. Among women aged 50 years and older, the risks of NASH and advanced fibrosis were significantly higher, at 17% and 56%, respectively (RR, 1.17 and RR, 1.56). The sex-specific prevalence of advanced fibrosis was not significantly different in patients younger than 50 years.

“Our findings of an increased prevalence of severe phenotypes of NAFLD – NASH and advanced fibrosis – among older women fits well into the current understanding of disease pathogenesis,” the researchers noted.

The findings were limited by several factors, including the cross-sectional nature and heterogeneity of the included studies and lack of data on possible contributions to NASH and NAFLD such as polycystic ovarian syndrome, cumulative use of hormone therapy, and pregnancy, the researchers noted.

However, the results were strengthened by the large patient population. “Given the higher risk of advanced fibrosis observed among women compared to men with NAFLD in our meta-analysis, it is plausible that cirrhosis and its complications may occur with greater frequency among women than in men,” the researchers said. Consequently, women older than 50 years with NAFLD should be evaluated frequently for advanced disease, they noted. In addition, “more focused and intensified efforts may be warranted to target lifestyle modifications and weight loss among young women with NAFLD, particularly in the presence of NASH and/or advanced fibrosis,” the researchers concluded.

Conducting the study at this time was important because of conjectures of sex-based differences in NAFLD prevalence and NAFLD progression, Dr. Balakrishnan said in an interview. “However, the findings from studies conducted across different study populations have been disparate. Therefore, it was important to perform a systematic review and meta-analysis to determine whether there are differences in NAFLD and NAFLD severity risk between the [sexes],” she said.

Dr. Balakrishnan said she was surprised by the higher risk of severe NASH fibrosis in women compared with men once NAFLD is established. “This was surprising and sets NAFLD apart from other highly prevalent chronic liver disease etiologies,” she said. “Other common liver diseases, for example hepatitis B and hepatitis C, tend to be more common among men and tend to progress more rapidly, and tend to be more severe among men compared to women,” she noted.

The take-home message for clinicians is that NAFLD is at least equally, if not more, aggressive in women compared with men, and should be evaluated with equal aggressiveness, Dr. Balakrishnan emphasized. “Moreover, in the future we may expect to see the burden of cirrhosis distributed more equally among women and men than we have to date. This has implications for liver disease screening and women’s health,” she said. The next steps for research are to determine the specific reasons for the higher risk of NAFLD fibrosis in women compared with men, she added.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

SOURCE: Balakrishnan M et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.067.

AGA offers education on the latest challenges, trends and solutions for diagnosing and managing nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) at http://ow.ly/Bz1Q30qYMw0. Help your patients better understand their risk of NASH and NAFLD by sharing AGA patient education at http://ow.ly/GoY630qYOmY.

Women have a lower risk of nonalcoholic fatty liver disease compared with men, but those who do develop the disease are significantly more likely than are men to develop advanced fibrosis, according to data from a meta-analysis of more than 62,000 individuals.

Sex disparity persists in most chronic liver diseases, with more cases and risk of progression reported in men, but the effect of sex on nonalcoholic fatty liver disease (NAFLD) remains unclear, wrote Maya Balakrishnan, MD, of Baylor College of Medicine, Houston, and colleagues. “Knowing whether and how [sex] influences the risk and severity of NAFLD is important for risk stratification, risk modification as well as prognostication,” they said.

In a study published in Clinical Gastroenterology and Hepatology, the researchers conducted a review and meta-analysis of 54 studies, including data from 62,239 patients with NAFLD, 5,428 with nonalcoholic steatohepatitis (NASH), and 6,444 with advanced NAFLD fibrosis.

Overall, women had a 19% lower risk of developing NAFLD compared with men (pooled risk ratio 0.81), a similar risk to men of developing NASH (RR, 1.00), and a 37% increased risk of advanced fibrosis (RR, 1.37) compared with men.

The risk of more severe disease in women increased with age. Among women aged 50 years and older, the risks of NASH and advanced fibrosis were significantly higher, at 17% and 56%, respectively (RR, 1.17 and RR, 1.56). The sex-specific prevalence of advanced fibrosis was not significantly different in patients younger than 50 years.

“Our findings of an increased prevalence of severe phenotypes of NAFLD – NASH and advanced fibrosis – among older women fits well into the current understanding of disease pathogenesis,” the researchers noted.

The findings were limited by several factors, including the cross-sectional nature and heterogeneity of the included studies and lack of data on possible contributions to NASH and NAFLD such as polycystic ovarian syndrome, cumulative use of hormone therapy, and pregnancy, the researchers noted.

However, the results were strengthened by the large patient population. “Given the higher risk of advanced fibrosis observed among women compared to men with NAFLD in our meta-analysis, it is plausible that cirrhosis and its complications may occur with greater frequency among women than in men,” the researchers said. Consequently, women older than 50 years with NAFLD should be evaluated frequently for advanced disease, they noted. In addition, “more focused and intensified efforts may be warranted to target lifestyle modifications and weight loss among young women with NAFLD, particularly in the presence of NASH and/or advanced fibrosis,” the researchers concluded.

Conducting the study at this time was important because of conjectures of sex-based differences in NAFLD prevalence and NAFLD progression, Dr. Balakrishnan said in an interview. “However, the findings from studies conducted across different study populations have been disparate. Therefore, it was important to perform a systematic review and meta-analysis to determine whether there are differences in NAFLD and NAFLD severity risk between the [sexes],” she said.

Dr. Balakrishnan said she was surprised by the higher risk of severe NASH fibrosis in women compared with men once NAFLD is established. “This was surprising and sets NAFLD apart from other highly prevalent chronic liver disease etiologies,” she said. “Other common liver diseases, for example hepatitis B and hepatitis C, tend to be more common among men and tend to progress more rapidly, and tend to be more severe among men compared to women,” she noted.

The take-home message for clinicians is that NAFLD is at least equally, if not more, aggressive in women compared with men, and should be evaluated with equal aggressiveness, Dr. Balakrishnan emphasized. “Moreover, in the future we may expect to see the burden of cirrhosis distributed more equally among women and men than we have to date. This has implications for liver disease screening and women’s health,” she said. The next steps for research are to determine the specific reasons for the higher risk of NAFLD fibrosis in women compared with men, she added.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

SOURCE: Balakrishnan M et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.067.

AGA offers education on the latest challenges, trends and solutions for diagnosing and managing nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) at http://ow.ly/Bz1Q30qYMw0. Help your patients better understand their risk of NASH and NAFLD by sharing AGA patient education at http://ow.ly/GoY630qYOmY.

Women have a lower risk of nonalcoholic fatty liver disease compared with men, but those who do develop the disease are significantly more likely than are men to develop advanced fibrosis, according to data from a meta-analysis of more than 62,000 individuals.

Sex disparity persists in most chronic liver diseases, with more cases and risk of progression reported in men, but the effect of sex on nonalcoholic fatty liver disease (NAFLD) remains unclear, wrote Maya Balakrishnan, MD, of Baylor College of Medicine, Houston, and colleagues. “Knowing whether and how [sex] influences the risk and severity of NAFLD is important for risk stratification, risk modification as well as prognostication,” they said.

In a study published in Clinical Gastroenterology and Hepatology, the researchers conducted a review and meta-analysis of 54 studies, including data from 62,239 patients with NAFLD, 5,428 with nonalcoholic steatohepatitis (NASH), and 6,444 with advanced NAFLD fibrosis.

Overall, women had a 19% lower risk of developing NAFLD compared with men (pooled risk ratio 0.81), a similar risk to men of developing NASH (RR, 1.00), and a 37% increased risk of advanced fibrosis (RR, 1.37) compared with men.

The risk of more severe disease in women increased with age. Among women aged 50 years and older, the risks of NASH and advanced fibrosis were significantly higher, at 17% and 56%, respectively (RR, 1.17 and RR, 1.56). The sex-specific prevalence of advanced fibrosis was not significantly different in patients younger than 50 years.

“Our findings of an increased prevalence of severe phenotypes of NAFLD – NASH and advanced fibrosis – among older women fits well into the current understanding of disease pathogenesis,” the researchers noted.

The findings were limited by several factors, including the cross-sectional nature and heterogeneity of the included studies and lack of data on possible contributions to NASH and NAFLD such as polycystic ovarian syndrome, cumulative use of hormone therapy, and pregnancy, the researchers noted.

However, the results were strengthened by the large patient population. “Given the higher risk of advanced fibrosis observed among women compared to men with NAFLD in our meta-analysis, it is plausible that cirrhosis and its complications may occur with greater frequency among women than in men,” the researchers said. Consequently, women older than 50 years with NAFLD should be evaluated frequently for advanced disease, they noted. In addition, “more focused and intensified efforts may be warranted to target lifestyle modifications and weight loss among young women with NAFLD, particularly in the presence of NASH and/or advanced fibrosis,” the researchers concluded.

Conducting the study at this time was important because of conjectures of sex-based differences in NAFLD prevalence and NAFLD progression, Dr. Balakrishnan said in an interview. “However, the findings from studies conducted across different study populations have been disparate. Therefore, it was important to perform a systematic review and meta-analysis to determine whether there are differences in NAFLD and NAFLD severity risk between the [sexes],” she said.

Dr. Balakrishnan said she was surprised by the higher risk of severe NASH fibrosis in women compared with men once NAFLD is established. “This was surprising and sets NAFLD apart from other highly prevalent chronic liver disease etiologies,” she said. “Other common liver diseases, for example hepatitis B and hepatitis C, tend to be more common among men and tend to progress more rapidly, and tend to be more severe among men compared to women,” she noted.

The take-home message for clinicians is that NAFLD is at least equally, if not more, aggressive in women compared with men, and should be evaluated with equal aggressiveness, Dr. Balakrishnan emphasized. “Moreover, in the future we may expect to see the burden of cirrhosis distributed more equally among women and men than we have to date. This has implications for liver disease screening and women’s health,” she said. The next steps for research are to determine the specific reasons for the higher risk of NAFLD fibrosis in women compared with men, she added.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

SOURCE: Balakrishnan M et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.067.

AGA offers education on the latest challenges, trends and solutions for diagnosing and managing nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) at http://ow.ly/Bz1Q30qYMw0. Help your patients better understand their risk of NASH and NAFLD by sharing AGA patient education at http://ow.ly/GoY630qYOmY.

Women have a lower risk of nonalcoholic fatty liver disease compared with men, but those who do develop the disease are significantly more likely than are men to develop advanced fibrosis, according to data from a meta-analysis of more than 62,000 individuals.

Sex disparity persists in most chronic liver diseases, with more cases and risk of progression reported in men, but the effect of sex on nonalcoholic fatty liver disease (NAFLD) remains unclear, wrote Maya Balakrishnan, MD, of Baylor College of Medicine, Houston, and colleagues. “Knowing whether and how [sex] influences the risk and severity of NAFLD is important for risk stratification, risk modification as well as prognostication,” they said.

In a study published in Clinical Gastroenterology and Hepatology, the researchers conducted a review and meta-analysis of 54 studies, including data from 62,239 patients with NAFLD, 5,428 with nonalcoholic steatohepatitis (NASH), and 6,444 with advanced NAFLD fibrosis.

Overall, women had a 19% lower risk of developing NAFLD compared with men (pooled risk ratio 0.81), a similar risk to men of developing NASH (RR, 1.00), and a 37% increased risk of advanced fibrosis (RR, 1.37) compared with men.

The risk of more severe disease in women increased with age. Among women aged 50 years and older, the risks of NASH and advanced fibrosis were significantly higher, at 17% and 56%, respectively (RR, 1.17 and RR, 1.56). The sex-specific prevalence of advanced fibrosis was not significantly different in patients younger than 50 years.

“Our findings of an increased prevalence of severe phenotypes of NAFLD – NASH and advanced fibrosis – among older women fits well into the current understanding of disease pathogenesis,” the researchers noted.

The findings were limited by several factors, including the cross-sectional nature and heterogeneity of the included studies and lack of data on possible contributions to NASH and NAFLD such as polycystic ovarian syndrome, cumulative use of hormone therapy, and pregnancy, the researchers noted.

However, the results were strengthened by the large patient population. “Given the higher risk of advanced fibrosis observed among women compared to men with NAFLD in our meta-analysis, it is plausible that cirrhosis and its complications may occur with greater frequency among women than in men,” the researchers said. Consequently, women older than 50 years with NAFLD should be evaluated frequently for advanced disease, they noted. In addition, “more focused and intensified efforts may be warranted to target lifestyle modifications and weight loss among young women with NAFLD, particularly in the presence of NASH and/or advanced fibrosis,” the researchers concluded.

Conducting the study at this time was important because of conjectures of sex-based differences in NAFLD prevalence and NAFLD progression, Dr. Balakrishnan said in an interview. “However, the findings from studies conducted across different study populations have been disparate. Therefore, it was important to perform a systematic review and meta-analysis to determine whether there are differences in NAFLD and NAFLD severity risk between the [sexes],” she said.

Dr. Balakrishnan said she was surprised by the higher risk of severe NASH fibrosis in women compared with men once NAFLD is established. “This was surprising and sets NAFLD apart from other highly prevalent chronic liver disease etiologies,” she said. “Other common liver diseases, for example hepatitis B and hepatitis C, tend to be more common among men and tend to progress more rapidly, and tend to be more severe among men compared to women,” she noted.

The take-home message for clinicians is that NAFLD is at least equally, if not more, aggressive in women compared with men, and should be evaluated with equal aggressiveness, Dr. Balakrishnan emphasized. “Moreover, in the future we may expect to see the burden of cirrhosis distributed more equally among women and men than we have to date. This has implications for liver disease screening and women’s health,” she said. The next steps for research are to determine the specific reasons for the higher risk of NAFLD fibrosis in women compared with men, she added.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

SOURCE: Balakrishnan M et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.067.

Women have a lower risk of nonalcoholic fatty liver disease compared with men, but those who do develop the disease are significantly more likely than are men to develop advanced fibrosis, according to data from a meta-analysis of more than 62,000 individuals.

Sex disparity persists in most chronic liver diseases, with more cases and risk of progression reported in men, but the effect of sex on nonalcoholic fatty liver disease (NAFLD) remains unclear, wrote Maya Balakrishnan, MD, of Baylor College of Medicine, Houston, and colleagues. “Knowing whether and how [sex] influences the risk and severity of NAFLD is important for risk stratification, risk modification as well as prognostication,” they said.

In a study published in Clinical Gastroenterology and Hepatology, the researchers conducted a review and meta-analysis of 54 studies, including data from 62,239 patients with NAFLD, 5,428 with nonalcoholic steatohepatitis (NASH), and 6,444 with advanced NAFLD fibrosis.

Overall, women had a 19% lower risk of developing NAFLD compared with men (pooled risk ratio 0.81), a similar risk to men of developing NASH (RR, 1.00), and a 37% increased risk of advanced fibrosis (RR, 1.37) compared with men.

The risk of more severe disease in women increased with age. Among women aged 50 years and older, the risks of NASH and advanced fibrosis were significantly higher, at 17% and 56%, respectively (RR, 1.17 and RR, 1.56). The sex-specific prevalence of advanced fibrosis was not significantly different in patients younger than 50 years.

“Our findings of an increased prevalence of severe phenotypes of NAFLD – NASH and advanced fibrosis – among older women fits well into the current understanding of disease pathogenesis,” the researchers noted.

The findings were limited by several factors, including the cross-sectional nature and heterogeneity of the included studies and lack of data on possible contributions to NASH and NAFLD such as polycystic ovarian syndrome, cumulative use of hormone therapy, and pregnancy, the researchers noted.

However, the results were strengthened by the large patient population. “Given the higher risk of advanced fibrosis observed among women compared to men with NAFLD in our meta-analysis, it is plausible that cirrhosis and its complications may occur with greater frequency among women than in men,” the researchers said. Consequently, women older than 50 years with NAFLD should be evaluated frequently for advanced disease, they noted. In addition, “more focused and intensified efforts may be warranted to target lifestyle modifications and weight loss among young women with NAFLD, particularly in the presence of NASH and/or advanced fibrosis,” the researchers concluded.

Conducting the study at this time was important because of conjectures of sex-based differences in NAFLD prevalence and NAFLD progression, Dr. Balakrishnan said in an interview. “However, the findings from studies conducted across different study populations have been disparate. Therefore, it was important to perform a systematic review and meta-analysis to determine whether there are differences in NAFLD and NAFLD severity risk between the [sexes],” she said.

Dr. Balakrishnan said she was surprised by the higher risk of severe NASH fibrosis in women compared with men once NAFLD is established. “This was surprising and sets NAFLD apart from other highly prevalent chronic liver disease etiologies,” she said. “Other common liver diseases, for example hepatitis B and hepatitis C, tend to be more common among men and tend to progress more rapidly, and tend to be more severe among men compared to women,” she noted.

The take-home message for clinicians is that NAFLD is at least equally, if not more, aggressive in women compared with men, and should be evaluated with equal aggressiveness, Dr. Balakrishnan emphasized. “Moreover, in the future we may expect to see the burden of cirrhosis distributed more equally among women and men than we have to date. This has implications for liver disease screening and women’s health,” she said. The next steps for research are to determine the specific reasons for the higher risk of NAFLD fibrosis in women compared with men, she added.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

SOURCE: Balakrishnan M et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.067.

Women have a lower risk of nonalcoholic fatty liver disease compared with men, but those who do develop the disease are significantly more likely than are men to develop advanced fibrosis, according to data from a meta-analysis of more than 62,000 individuals.

Sex disparity persists in most chronic liver diseases, with more cases and risk of progression reported in men, but the effect of sex on nonalcoholic fatty liver disease (NAFLD) remains unclear, wrote Maya Balakrishnan, MD, of Baylor College of Medicine, Houston, and colleagues. “Knowing whether and how [sex] influences the risk and severity of NAFLD is important for risk stratification, risk modification as well as prognostication,” they said.

In a study published in Clinical Gastroenterology and Hepatology, the researchers conducted a review and meta-analysis of 54 studies, including data from 62,239 patients with NAFLD, 5,428 with nonalcoholic steatohepatitis (NASH), and 6,444 with advanced NAFLD fibrosis.

Overall, women had a 19% lower risk of developing NAFLD compared with men (pooled risk ratio 0.81), a similar risk to men of developing NASH (RR, 1.00), and a 37% increased risk of advanced fibrosis (RR, 1.37) compared with men.

The risk of more severe disease in women increased with age. Among women aged 50 years and older, the risks of NASH and advanced fibrosis were significantly higher, at 17% and 56%, respectively (RR, 1.17 and RR, 1.56). The sex-specific prevalence of advanced fibrosis was not significantly different in patients younger than 50 years.

“Our findings of an increased prevalence of severe phenotypes of NAFLD – NASH and advanced fibrosis – among older women fits well into the current understanding of disease pathogenesis,” the researchers noted.

The findings were limited by several factors, including the cross-sectional nature and heterogeneity of the included studies and lack of data on possible contributions to NASH and NAFLD such as polycystic ovarian syndrome, cumulative use of hormone therapy, and pregnancy, the researchers noted.

However, the results were strengthened by the large patient population. “Given the higher risk of advanced fibrosis observed among women compared to men with NAFLD in our meta-analysis, it is plausible that cirrhosis and its complications may occur with greater frequency among women than in men,” the researchers said. Consequently, women older than 50 years with NAFLD should be evaluated frequently for advanced disease, they noted. In addition, “more focused and intensified efforts may be warranted to target lifestyle modifications and weight loss among young women with NAFLD, particularly in the presence of NASH and/or advanced fibrosis,” the researchers concluded.

Conducting the study at this time was important because of conjectures of sex-based differences in NAFLD prevalence and NAFLD progression, Dr. Balakrishnan said in an interview. “However, the findings from studies conducted across different study populations have been disparate. Therefore, it was important to perform a systematic review and meta-analysis to determine whether there are differences in NAFLD and NAFLD severity risk between the [sexes],” she said.

Dr. Balakrishnan said she was surprised by the higher risk of severe NASH fibrosis in women compared with men once NAFLD is established. “This was surprising and sets NAFLD apart from other highly prevalent chronic liver disease etiologies,” she said. “Other common liver diseases, for example hepatitis B and hepatitis C, tend to be more common among men and tend to progress more rapidly, and tend to be more severe among men compared to women,” she noted.

The take-home message for clinicians is that NAFLD is at least equally, if not more, aggressive in women compared with men, and should be evaluated with equal aggressiveness, Dr. Balakrishnan emphasized. “Moreover, in the future we may expect to see the burden of cirrhosis distributed more equally among women and men than we have to date. This has implications for liver disease screening and women’s health,” she said. The next steps for research are to determine the specific reasons for the higher risk of NAFLD fibrosis in women compared with men, she added.

The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.

SOURCE: Balakrishnan M et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.067.

Adding subcutaneous nemolizumab to topical treatments for atopic dermatitis patients significantly improved their itching, compared with a placebo, in a phase 3 study of 215 patients in Japan.

Controlling the pruritus associated with atopic dermatitis (AD) can have a significant impact on patients’ quality of life, wrote Kenji Kabashima, MD, PhD, of the department of dermatology at Kyoto University, and coauthors. Frequent scratching can cause not only mechanical skin damage, but also may enhance inflammatory reactions and contribute to sleep problems.

In earlier phase studies, nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A, showed efficacy in reducing pruritus in patients with AD, but has not been well studied in patients who are also using topical agents, they wrote.

In the study published in the New England Journal of Medicine, the researchers randomized 143 patients with AD and moderate to severe pruritus to 60 mg of subcutaneous nemolizumab and 72 patients to a placebo every 4 weeks for 16 weeks. All patients were aged 13 years and older with a confirmed AD diagnosis and a history of inadequate response to or inability to use treatments, including topical glucocorticoids and oral antihistamines. Their average age was 40 years, approximately two-thirds were male, and the average disease duration was approximately 30 years. Topical treatments included a medium potency glucocorticoid in 97% of patients in both groups, and a topical calcineurin inhibitor in 41% of those on nemolizumab, and 40% of those on placebo; almost 90% of the patients in both groups were on oral antihistamines.

At 16 weeks, scores on the visual analog scale for pruritus (the primary outcome) significantly improved from baseline in the nemolizumab group, compared with the placebo group (a mean change of –42.8% and –21.4%, respectively, P < .001).

In addition, more patients in the nemolizumab group, compared with the placebo group (40% vs. 22%) achieved a score of 4 or less on the Dermatology Life Quality Index, with lower scores reflecting less impact of disease on daily life. In addition, more patients in the nemolizumab group, compared with the placebo group (55% vs. 21%) achieved a score of 7 or less on the Insomnia Severity Index.

During the study, 71% of the patients in each group reported adverse events, most were mild or moderate. The most common adverse event was worsening AD, reported by 24% of the nemolizumab patients and 21% of the placebo patients. Reactions related to the injection occurred in 8% of nemolizumab patients and 3% of placebo patients. Cytokine abnormalities, which included an increased level of thymus and activation regulated chemokine, were reported in 10 (7%) of the patients on nemolizumab, none of which occurred in those on placebo. “Most were not accompanied by a worsening of signs of or the extent of atopic dermatitis,” the authors wrote.

Severe adverse events were reported in three patients (2%) in the nemolizumab group, which were Meniere’s disease, acute pancreatitis, and AD in one patient each. No severe adverse events were reported in the placebo group. In addition, three patients in the nemolizumab group experienced four treatment-related adverse events that led them to discontinue treatment: AD, Meniere’s disease, alopecia, and peripheral edema.

The study findings were limited by several factors including the relatively short treatment period, inclusion only of Japanese patients, inclusion of patients aged as young as 13 years, and the inability to draw conclusions from the secondary endpoints such as quality of life and sleep issues, the researchers noted.

However, the results suggest that “nemolizumab plus topical agents may ameliorate both pruritus and signs of eczema and may lessen the severity of atopic dermatitis by disrupting the itch-scratch cycle,” they added.

“Novel therapies [for AD] are needed, as there are still patients who need better disease control despite current therapies, and AD is a heterogeneous disease that may need different treatment approaches,” Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview.

Dr. Simpson, who was not an investigator in this study, said that he was somewhat surprised that the itch reduction was lower in the current study, compared with previous studies by the same group. Also surprising was the increase in cytokine abnormalities in the nemolizumab group, which “needs further study.”

Overall, the data “provide support that blockade of the IL-31 receptor improves itch in AD and appears to have some effect on inflammation,” Dr. Simpson said.

One challenge to the clinical use of nemolizumab will be identifying “where this type of drug fits into the treatment paradigm,” and determining whether specific patients whose disease is driven more by this neuroimmune pathway could benefit more than with the traditional IL-4 or IL-13 blockade, he said.

The study was supported by Maruho. Dr. Kabashima disclosed consulting fees from Maruho and two coauthors were Maruho employees. Dr. Simpson had no financial conflicts relevant to this study, but he reported receiving research grants and other financial relationships with manufacturers of AD therapies.

SOURCE: Kabashima K et al. N Engl J Med. 2020 Jul 9. doi: 10.1056/NEJMoa1917006.

Adding subcutaneous nemolizumab to topical treatments for atopic dermatitis patients significantly improved their itching, compared with a placebo, in a phase 3 study of 215 patients in Japan.

Controlling the pruritus associated with atopic dermatitis (AD) can have a significant impact on patients’ quality of life, wrote Kenji Kabashima, MD, PhD, of the department of dermatology at Kyoto University, and coauthors. Frequent scratching can cause not only mechanical skin damage, but also may enhance inflammatory reactions and contribute to sleep problems.

In earlier phase studies, nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A, showed efficacy in reducing pruritus in patients with AD, but has not been well studied in patients who are also using topical agents, they wrote.

In the study published in the New England Journal of Medicine, the researchers randomized 143 patients with AD and moderate to severe pruritus to 60 mg of subcutaneous nemolizumab and 72 patients to a placebo every 4 weeks for 16 weeks. All patients were aged 13 years and older with a confirmed AD diagnosis and a history of inadequate response to or inability to use treatments, including topical glucocorticoids and oral antihistamines. Their average age was 40 years, approximately two-thirds were male, and the average disease duration was approximately 30 years. Topical treatments included a medium potency glucocorticoid in 97% of patients in both groups, and a topical calcineurin inhibitor in 41% of those on nemolizumab, and 40% of those on placebo; almost 90% of the patients in both groups were on oral antihistamines.

At 16 weeks, scores on the visual analog scale for pruritus (the primary outcome) significantly improved from baseline in the nemolizumab group, compared with the placebo group (a mean change of –42.8% and –21.4%, respectively, P < .001).

In addition, more patients in the nemolizumab group, compared with the placebo group (40% vs. 22%) achieved a score of 4 or less on the Dermatology Life Quality Index, with lower scores reflecting less impact of disease on daily life. In addition, more patients in the nemolizumab group, compared with the placebo group (55% vs. 21%) achieved a score of 7 or less on the Insomnia Severity Index.

During the study, 71% of the patients in each group reported adverse events, most were mild or moderate. The most common adverse event was worsening AD, reported by 24% of the nemolizumab patients and 21% of the placebo patients. Reactions related to the injection occurred in 8% of nemolizumab patients and 3% of placebo patients. Cytokine abnormalities, which included an increased level of thymus and activation regulated chemokine, were reported in 10 (7%) of the patients on nemolizumab, none of which occurred in those on placebo. “Most were not accompanied by a worsening of signs of or the extent of atopic dermatitis,” the authors wrote.

Severe adverse events were reported in three patients (2%) in the nemolizumab group, which were Meniere’s disease, acute pancreatitis, and AD in one patient each. No severe adverse events were reported in the placebo group. In addition, three patients in the nemolizumab group experienced four treatment-related adverse events that led them to discontinue treatment: AD, Meniere’s disease, alopecia, and peripheral edema.

The study findings were limited by several factors including the relatively short treatment period, inclusion only of Japanese patients, inclusion of patients aged as young as 13 years, and the inability to draw conclusions from the secondary endpoints such as quality of life and sleep issues, the researchers noted.

However, the results suggest that “nemolizumab plus topical agents may ameliorate both pruritus and signs of eczema and may lessen the severity of atopic dermatitis by disrupting the itch-scratch cycle,” they added.

“Novel therapies [for AD] are needed, as there are still patients who need better disease control despite current therapies, and AD is a heterogeneous disease that may need different treatment approaches,” Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview.

Dr. Simpson, who was not an investigator in this study, said that he was somewhat surprised that the itch reduction was lower in the current study, compared with previous studies by the same group. Also surprising was the increase in cytokine abnormalities in the nemolizumab group, which “needs further study.”

Overall, the data “provide support that blockade of the IL-31 receptor improves itch in AD and appears to have some effect on inflammation,” Dr. Simpson said.

One challenge to the clinical use of nemolizumab will be identifying “where this type of drug fits into the treatment paradigm,” and determining whether specific patients whose disease is driven more by this neuroimmune pathway could benefit more than with the traditional IL-4 or IL-13 blockade, he said.

The study was supported by Maruho. Dr. Kabashima disclosed consulting fees from Maruho and two coauthors were Maruho employees. Dr. Simpson had no financial conflicts relevant to this study, but he reported receiving research grants and other financial relationships with manufacturers of AD therapies.

SOURCE: Kabashima K et al. N Engl J Med. 2020 Jul 9. doi: 10.1056/NEJMoa1917006.

Adding subcutaneous nemolizumab to topical treatments for atopic dermatitis patients significantly improved their itching, compared with a placebo, in a phase 3 study of 215 patients in Japan.

Controlling the pruritus associated with atopic dermatitis (AD) can have a significant impact on patients’ quality of life, wrote Kenji Kabashima, MD, PhD, of the department of dermatology at Kyoto University, and coauthors. Frequent scratching can cause not only mechanical skin damage, but also may enhance inflammatory reactions and contribute to sleep problems.

In earlier phase studies, nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A, showed efficacy in reducing pruritus in patients with AD, but has not been well studied in patients who are also using topical agents, they wrote.

In the study published in the New England Journal of Medicine, the researchers randomized 143 patients with AD and moderate to severe pruritus to 60 mg of subcutaneous nemolizumab and 72 patients to a placebo every 4 weeks for 16 weeks. All patients were aged 13 years and older with a confirmed AD diagnosis and a history of inadequate response to or inability to use treatments, including topical glucocorticoids and oral antihistamines. Their average age was 40 years, approximately two-thirds were male, and the average disease duration was approximately 30 years. Topical treatments included a medium potency glucocorticoid in 97% of patients in both groups, and a topical calcineurin inhibitor in 41% of those on nemolizumab, and 40% of those on placebo; almost 90% of the patients in both groups were on oral antihistamines.

At 16 weeks, scores on the visual analog scale for pruritus (the primary outcome) significantly improved from baseline in the nemolizumab group, compared with the placebo group (a mean change of –42.8% and –21.4%, respectively, P < .001).

In addition, more patients in the nemolizumab group, compared with the placebo group (40% vs. 22%) achieved a score of 4 or less on the Dermatology Life Quality Index, with lower scores reflecting less impact of disease on daily life. In addition, more patients in the nemolizumab group, compared with the placebo group (55% vs. 21%) achieved a score of 7 or less on the Insomnia Severity Index.

During the study, 71% of the patients in each group reported adverse events, most were mild or moderate. The most common adverse event was worsening AD, reported by 24% of the nemolizumab patients and 21% of the placebo patients. Reactions related to the injection occurred in 8% of nemolizumab patients and 3% of placebo patients. Cytokine abnormalities, which included an increased level of thymus and activation regulated chemokine, were reported in 10 (7%) of the patients on nemolizumab, none of which occurred in those on placebo. “Most were not accompanied by a worsening of signs of or the extent of atopic dermatitis,” the authors wrote.

Severe adverse events were reported in three patients (2%) in the nemolizumab group, which were Meniere’s disease, acute pancreatitis, and AD in one patient each. No severe adverse events were reported in the placebo group. In addition, three patients in the nemolizumab group experienced four treatment-related adverse events that led them to discontinue treatment: AD, Meniere’s disease, alopecia, and peripheral edema.

The study findings were limited by several factors including the relatively short treatment period, inclusion only of Japanese patients, inclusion of patients aged as young as 13 years, and the inability to draw conclusions from the secondary endpoints such as quality of life and sleep issues, the researchers noted.

However, the results suggest that “nemolizumab plus topical agents may ameliorate both pruritus and signs of eczema and may lessen the severity of atopic dermatitis by disrupting the itch-scratch cycle,” they added.

“Novel therapies [for AD] are needed, as there are still patients who need better disease control despite current therapies, and AD is a heterogeneous disease that may need different treatment approaches,” Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview.

Dr. Simpson, who was not an investigator in this study, said that he was somewhat surprised that the itch reduction was lower in the current study, compared with previous studies by the same group. Also surprising was the increase in cytokine abnormalities in the nemolizumab group, which “needs further study.”

Overall, the data “provide support that blockade of the IL-31 receptor improves itch in AD and appears to have some effect on inflammation,” Dr. Simpson said.

One challenge to the clinical use of nemolizumab will be identifying “where this type of drug fits into the treatment paradigm,” and determining whether specific patients whose disease is driven more by this neuroimmune pathway could benefit more than with the traditional IL-4 or IL-13 blockade, he said.

The study was supported by Maruho. Dr. Kabashima disclosed consulting fees from Maruho and two coauthors were Maruho employees. Dr. Simpson had no financial conflicts relevant to this study, but he reported receiving research grants and other financial relationships with manufacturers of AD therapies.

SOURCE: Kabashima K et al. N Engl J Med. 2020 Jul 9. doi: 10.1056/NEJMoa1917006.

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children appear less likely than adults to be the first cases of COVID-19 within a household, based on data from families of 39 children younger than 16 years.

Courtesy NIAID

“Unlike with other viral respiratory infections, children do not seem to be a major vector of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, with most pediatric cases described inside familial clusters and no documentation of child-to-child or child-to-adult transmission,” said Klara M. Posfay-Barbe, MD, of the University of Geneva, Switzerland, and colleagues.

In a study published in Pediatrics, the researchers analyzed data from all COVID-19 patients younger than 16 years who were identified between March 10, 2020, and April 10, 2020, through a hospital surveillance network. Parents and household contacts were called for contact tracing.

In 31 of 39 (79%) households, at least one adult family member had a suspected or confirmed SARS-CoV-2 infection before onset of symptoms in the child. These findings support data from previous studies suggesting that children mainly become infected from adult family members rather than transmitting the virus to them, the researchers said

In only 3 of 39 (8%) households was the study child the first to develop symptoms. “Surprisingly, in 33% of households, symptomatic HHCs [household contacts] tested negative despite belonging to a familial cluster with confirmed SARS-CoV-2 cases, suggesting an underreporting of cases,” Dr. Posfay-Barbe and associates noted.

The findings were limited by several factors including potential underreporting of cases because those with mild or atypical presentations may not have sought medical care, and the inability to confirm child-to-adult transmission. The results were strengthened by the extensive contact tracing and very few individuals lost to follow-up, they said; however, more diagnostic screening and contact tracing are needed to improve understanding of household transmission of SARS-CoV-2, they concluded.

Resolving the issue of how much children contribute to transmission of SARS-CoV-2 is essential to making informed decisions about public health, including how to structure schools and child-care facility reopening, Benjamin Lee, MD, and William V. Raszka Jr., MD, both of the University of Vermont, Burlington, said in an accompanying editorial (Pediatrics. 2020 Jul 10. doi: 10.1542/peds/2020-004879).

The data in the current study support other studies of transmission among household contacts in China suggesting that, in most cases of childhood infections, “the child was not the source of infection and that children most frequently acquire COVID-19 from adults, rather than transmitting it to them,” they wrote.

In addition, the limited data on transmission of SARS-CoV-2 by children outside of the household show few cases of secondary infection from children identified with SARS-CoV-2 in school settings in studies from France and Australia, Dr. Lee and Dr. Raszka noted.

“On the basis of these data, SARS-CoV2 transmission in schools may be less important in community transmission than initially feared,” the editorialists wrote. “This would be another manner by which SARS-CoV2 differs drastically from influenza, for which school-based transmission is well recognized as a significant driver of epidemic disease and forms the basis for most evidence regarding school closures as public health strategy.”

“Therefore, serious consideration should be paid toward strategies that allow schools to remain open, even during periods of COVID-19 spread,” the editorialists concluded. “In doing so, we could minimize the potentially profound adverse social, developmental, and health costs that our children will continue to suffer until an effective treatment or vaccine can be developed and distributed or, failing that, until we reach herd immunity,” Dr. Lee and Dr. Raszka emphasized.

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

SOURCE: Posfay-Barbe KM et al. Pediatrics. 2020 Jul 10. doi: 10.1542/peds.2020-1576.

Children appear less likely than adults to be the first cases of COVID-19 within a household, based on data from families of 39 children younger than 16 years.

Courtesy NIAID

“Unlike with other viral respiratory infections, children do not seem to be a major vector of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, with most pediatric cases described inside familial clusters and no documentation of child-to-child or child-to-adult transmission,” said Klara M. Posfay-Barbe, MD, of the University of Geneva, Switzerland, and colleagues.

In a study published in Pediatrics, the researchers analyzed data from all COVID-19 patients younger than 16 years who were identified between March 10, 2020, and April 10, 2020, through a hospital surveillance network. Parents and household contacts were called for contact tracing.

In 31 of 39 (79%) households, at least one adult family member had a suspected or confirmed SARS-CoV-2 infection before onset of symptoms in the child. These findings support data from previous studies suggesting that children mainly become infected from adult family members rather than transmitting the virus to them, the researchers said

In only 3 of 39 (8%) households was the study child the first to develop symptoms. “Surprisingly, in 33% of households, symptomatic HHCs [household contacts] tested negative despite belonging to a familial cluster with confirmed SARS-CoV-2 cases, suggesting an underreporting of cases,” Dr. Posfay-Barbe and associates noted.

The findings were limited by several factors including potential underreporting of cases because those with mild or atypical presentations may not have sought medical care, and the inability to confirm child-to-adult transmission. The results were strengthened by the extensive contact tracing and very few individuals lost to follow-up, they said; however, more diagnostic screening and contact tracing are needed to improve understanding of household transmission of SARS-CoV-2, they concluded.

Resolving the issue of how much children contribute to transmission of SARS-CoV-2 is essential to making informed decisions about public health, including how to structure schools and child-care facility reopening, Benjamin Lee, MD, and William V. Raszka Jr., MD, both of the University of Vermont, Burlington, said in an accompanying editorial (Pediatrics. 2020 Jul 10. doi: 10.1542/peds/2020-004879).

The data in the current study support other studies of transmission among household contacts in China suggesting that, in most cases of childhood infections, “the child was not the source of infection and that children most frequently acquire COVID-19 from adults, rather than transmitting it to them,” they wrote.

In addition, the limited data on transmission of SARS-CoV-2 by children outside of the household show few cases of secondary infection from children identified with SARS-CoV-2 in school settings in studies from France and Australia, Dr. Lee and Dr. Raszka noted.

“On the basis of these data, SARS-CoV2 transmission in schools may be less important in community transmission than initially feared,” the editorialists wrote. “This would be another manner by which SARS-CoV2 differs drastically from influenza, for which school-based transmission is well recognized as a significant driver of epidemic disease and forms the basis for most evidence regarding school closures as public health strategy.”

“Therefore, serious consideration should be paid toward strategies that allow schools to remain open, even during periods of COVID-19 spread,” the editorialists concluded. “In doing so, we could minimize the potentially profound adverse social, developmental, and health costs that our children will continue to suffer until an effective treatment or vaccine can be developed and distributed or, failing that, until we reach herd immunity,” Dr. Lee and Dr. Raszka emphasized.

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

SOURCE: Posfay-Barbe KM et al. Pediatrics. 2020 Jul 10. doi: 10.1542/peds.2020-1576.

Children appear less likely than adults to be the first cases of COVID-19 within a household, based on data from families of 39 children younger than 16 years.

Courtesy NIAID

“Unlike with other viral respiratory infections, children do not seem to be a major vector of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, with most pediatric cases described inside familial clusters and no documentation of child-to-child or child-to-adult transmission,” said Klara M. Posfay-Barbe, MD, of the University of Geneva, Switzerland, and colleagues.

In a study published in Pediatrics, the researchers analyzed data from all COVID-19 patients younger than 16 years who were identified between March 10, 2020, and April 10, 2020, through a hospital surveillance network. Parents and household contacts were called for contact tracing.

In 31 of 39 (79%) households, at least one adult family member had a suspected or confirmed SARS-CoV-2 infection before onset of symptoms in the child. These findings support data from previous studies suggesting that children mainly become infected from adult family members rather than transmitting the virus to them, the researchers said

In only 3 of 39 (8%) households was the study child the first to develop symptoms. “Surprisingly, in 33% of households, symptomatic HHCs [household contacts] tested negative despite belonging to a familial cluster with confirmed SARS-CoV-2 cases, suggesting an underreporting of cases,” Dr. Posfay-Barbe and associates noted.

The findings were limited by several factors including potential underreporting of cases because those with mild or atypical presentations may not have sought medical care, and the inability to confirm child-to-adult transmission. The results were strengthened by the extensive contact tracing and very few individuals lost to follow-up, they said; however, more diagnostic screening and contact tracing are needed to improve understanding of household transmission of SARS-CoV-2, they concluded.

Resolving the issue of how much children contribute to transmission of SARS-CoV-2 is essential to making informed decisions about public health, including how to structure schools and child-care facility reopening, Benjamin Lee, MD, and William V. Raszka Jr., MD, both of the University of Vermont, Burlington, said in an accompanying editorial (Pediatrics. 2020 Jul 10. doi: 10.1542/peds/2020-004879).

The data in the current study support other studies of transmission among household contacts in China suggesting that, in most cases of childhood infections, “the child was not the source of infection and that children most frequently acquire COVID-19 from adults, rather than transmitting it to them,” they wrote.

In addition, the limited data on transmission of SARS-CoV-2 by children outside of the household show few cases of secondary infection from children identified with SARS-CoV-2 in school settings in studies from France and Australia, Dr. Lee and Dr. Raszka noted.

“On the basis of these data, SARS-CoV2 transmission in schools may be less important in community transmission than initially feared,” the editorialists wrote. “This would be another manner by which SARS-CoV2 differs drastically from influenza, for which school-based transmission is well recognized as a significant driver of epidemic disease and forms the basis for most evidence regarding school closures as public health strategy.”

“Therefore, serious consideration should be paid toward strategies that allow schools to remain open, even during periods of COVID-19 spread,” the editorialists concluded. “In doing so, we could minimize the potentially profound adverse social, developmental, and health costs that our children will continue to suffer until an effective treatment or vaccine can be developed and distributed or, failing that, until we reach herd immunity,” Dr. Lee and Dr. Raszka emphasized.

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

SOURCE: Posfay-Barbe KM et al. Pediatrics. 2020 Jul 10. doi: 10.1542/peds.2020-1576.