Heidi Splete

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.

Incorporating skin toxicity protocols at a cancer center significantly increased the rate of prophylactic treatment for rashes resulting from cancer therapies, and lowered the risk of interrupting or changing the dose of cancer treatment, according to the results of a retrospective study of 208 adults treated at the Dana-Farber Cancer Institute in Boston, or affiliated sites.

The benefits of prophylactic treatment for treatment-related skin rash in cancer patients are well established, based largely on the Skin Toxicity Evaluation Protocol With Panitumumab (STEPP) trial published in 2012, which led to the development of guidelines for preventing and managing skin toxicity associated with epidermal growth factor receptor inhibitor (EGFRi) treatment, wrote Zizi Yu of Harvard Medical School, Boston, and coauthors. However, they added, “awareness of and adherence to these guidelines among oncology clinicians are thus far poorly understood.” They pointed out that 90% of patients treated with an EGFRi develop cutaneous toxicities, which can affect quality of life, increase the risk of infection, and require dose modification, interruption, or discontinuation of treatment.

In the study, published in JAMA Dermatology, the researchers compared adherence to protocols at Dana-Farber before and after the 2014-2015 initiation of a Skin Toxicities from Anticancer Therapies (STAT) program at Dana-Farber established in 2014 by the department of dermatology.

The study population included 208 adult cancer patients with colorectal cancer, head and neck cancer, or cutaneous squamous cell cancer, treated with at least one dose of cetuximab (Erbitux); the average age of the patients was 62 years and the majority were men. Most had stage IV disease. The STAT program included the integration of 9 oncodermatologists in the head and neck, genitourinary, and cutaneous oncology clinics for 7 of 10 cancer treatment sessions per week, as well as the creation of urgent access time slots in oncodermatology clinics for 10 of 10 sessions per week.

Overall, significantly more patients were treated prophylactically for skin toxicity at the start of cetuximab treatment in 2017 vs. 2012 (47% vs. 25%, P less than .001) after the initiation of a dermatology protocol.

In addition, the preemptive use of tetracycline increased significantly from 45% to 71% (P = .02) between the two time periods, as did the use of topical corticosteroids (from 7% to 57%, P less than .001), while the use of topical antibiotics decreased from 79% to 43% (P = .02). Rates of dose changes or interruptions were significantly lower among those on prophylaxis (5% vs. 19%, P =.01), a 79% lower risk. Patients treated prophylactically were 94% less likely to need a first rescue treatment and 74% less likely to need a second rescue treatment for rash.

The study findings were limited by several factors including the retrospective design, use of data from a single institution, and incomplete documentation of some patients, the researchers noted. However, the results “highlight the value of integrating dermatologic care and education into oncology centers by increasing adherence to evidence-based prophylaxis protocols for rash and appropriate treatment agent selection, which may minimize toxicity-associated chemotherapy interruptions and improve quality of life,” they concluded.

“As novel cancer treatment options for patients continue to develop, and as patients with cancer live longer, the spectrum and prevalence of dermatologic toxic effects will continue to expand,” Bernice Y. Kwong, MD, director of the supportive dermato-oncology program at Stanford (Calif.) University, wrote in an accompanying editorial.

SOURCE: Yu Z et al. JAMA Dermatol. 2020 July 1. doi: 10.1001/jamadermatol.2020.1795. Kwong BY. JAMA Dermatol. 2020 Jul 1. doi: 10.1001/jamadermatol.2020.1794.

Incorporating skin toxicity protocols at a cancer center significantly increased the rate of prophylactic treatment for rashes resulting from cancer therapies, and lowered the risk of interrupting or changing the dose of cancer treatment, according to the results of a retrospective study of 208 adults treated at the Dana-Farber Cancer Institute in Boston, or affiliated sites.

The benefits of prophylactic treatment for treatment-related skin rash in cancer patients are well established, based largely on the Skin Toxicity Evaluation Protocol With Panitumumab (STEPP) trial published in 2012, which led to the development of guidelines for preventing and managing skin toxicity associated with epidermal growth factor receptor inhibitor (EGFRi) treatment, wrote Zizi Yu of Harvard Medical School, Boston, and coauthors. However, they added, “awareness of and adherence to these guidelines among oncology clinicians are thus far poorly understood.” They pointed out that 90% of patients treated with an EGFRi develop cutaneous toxicities, which can affect quality of life, increase the risk of infection, and require dose modification, interruption, or discontinuation of treatment.

In the study, published in JAMA Dermatology, the researchers compared adherence to protocols at Dana-Farber before and after the 2014-2015 initiation of a Skin Toxicities from Anticancer Therapies (STAT) program at Dana-Farber established in 2014 by the department of dermatology.

The study population included 208 adult cancer patients with colorectal cancer, head and neck cancer, or cutaneous squamous cell cancer, treated with at least one dose of cetuximab (Erbitux); the average age of the patients was 62 years and the majority were men. Most had stage IV disease. The STAT program included the integration of 9 oncodermatologists in the head and neck, genitourinary, and cutaneous oncology clinics for 7 of 10 cancer treatment sessions per week, as well as the creation of urgent access time slots in oncodermatology clinics for 10 of 10 sessions per week.

Overall, significantly more patients were treated prophylactically for skin toxicity at the start of cetuximab treatment in 2017 vs. 2012 (47% vs. 25%, P less than .001) after the initiation of a dermatology protocol.

In addition, the preemptive use of tetracycline increased significantly from 45% to 71% (P = .02) between the two time periods, as did the use of topical corticosteroids (from 7% to 57%, P less than .001), while the use of topical antibiotics decreased from 79% to 43% (P = .02). Rates of dose changes or interruptions were significantly lower among those on prophylaxis (5% vs. 19%, P =.01), a 79% lower risk. Patients treated prophylactically were 94% less likely to need a first rescue treatment and 74% less likely to need a second rescue treatment for rash.

The study findings were limited by several factors including the retrospective design, use of data from a single institution, and incomplete documentation of some patients, the researchers noted. However, the results “highlight the value of integrating dermatologic care and education into oncology centers by increasing adherence to evidence-based prophylaxis protocols for rash and appropriate treatment agent selection, which may minimize toxicity-associated chemotherapy interruptions and improve quality of life,” they concluded.

“As novel cancer treatment options for patients continue to develop, and as patients with cancer live longer, the spectrum and prevalence of dermatologic toxic effects will continue to expand,” Bernice Y. Kwong, MD, director of the supportive dermato-oncology program at Stanford (Calif.) University, wrote in an accompanying editorial.

SOURCE: Yu Z et al. JAMA Dermatol. 2020 July 1. doi: 10.1001/jamadermatol.2020.1795. Kwong BY. JAMA Dermatol. 2020 Jul 1. doi: 10.1001/jamadermatol.2020.1794.

Incorporating skin toxicity protocols at a cancer center significantly increased the rate of prophylactic treatment for rashes resulting from cancer therapies, and lowered the risk of interrupting or changing the dose of cancer treatment, according to the results of a retrospective study of 208 adults treated at the Dana-Farber Cancer Institute in Boston, or affiliated sites.

The benefits of prophylactic treatment for treatment-related skin rash in cancer patients are well established, based largely on the Skin Toxicity Evaluation Protocol With Panitumumab (STEPP) trial published in 2012, which led to the development of guidelines for preventing and managing skin toxicity associated with epidermal growth factor receptor inhibitor (EGFRi) treatment, wrote Zizi Yu of Harvard Medical School, Boston, and coauthors. However, they added, “awareness of and adherence to these guidelines among oncology clinicians are thus far poorly understood.” They pointed out that 90% of patients treated with an EGFRi develop cutaneous toxicities, which can affect quality of life, increase the risk of infection, and require dose modification, interruption, or discontinuation of treatment.

In the study, published in JAMA Dermatology, the researchers compared adherence to protocols at Dana-Farber before and after the 2014-2015 initiation of a Skin Toxicities from Anticancer Therapies (STAT) program at Dana-Farber established in 2014 by the department of dermatology.

The study population included 208 adult cancer patients with colorectal cancer, head and neck cancer, or cutaneous squamous cell cancer, treated with at least one dose of cetuximab (Erbitux); the average age of the patients was 62 years and the majority were men. Most had stage IV disease. The STAT program included the integration of 9 oncodermatologists in the head and neck, genitourinary, and cutaneous oncology clinics for 7 of 10 cancer treatment sessions per week, as well as the creation of urgent access time slots in oncodermatology clinics for 10 of 10 sessions per week.

Overall, significantly more patients were treated prophylactically for skin toxicity at the start of cetuximab treatment in 2017 vs. 2012 (47% vs. 25%, P less than .001) after the initiation of a dermatology protocol.

In addition, the preemptive use of tetracycline increased significantly from 45% to 71% (P = .02) between the two time periods, as did the use of topical corticosteroids (from 7% to 57%, P less than .001), while the use of topical antibiotics decreased from 79% to 43% (P = .02). Rates of dose changes or interruptions were significantly lower among those on prophylaxis (5% vs. 19%, P =.01), a 79% lower risk. Patients treated prophylactically were 94% less likely to need a first rescue treatment and 74% less likely to need a second rescue treatment for rash.

The study findings were limited by several factors including the retrospective design, use of data from a single institution, and incomplete documentation of some patients, the researchers noted. However, the results “highlight the value of integrating dermatologic care and education into oncology centers by increasing adherence to evidence-based prophylaxis protocols for rash and appropriate treatment agent selection, which may minimize toxicity-associated chemotherapy interruptions and improve quality of life,” they concluded.

“As novel cancer treatment options for patients continue to develop, and as patients with cancer live longer, the spectrum and prevalence of dermatologic toxic effects will continue to expand,” Bernice Y. Kwong, MD, director of the supportive dermato-oncology program at Stanford (Calif.) University, wrote in an accompanying editorial.

SOURCE: Yu Z et al. JAMA Dermatol. 2020 July 1. doi: 10.1001/jamadermatol.2020.1795. Kwong BY. JAMA Dermatol. 2020 Jul 1. doi: 10.1001/jamadermatol.2020.1794.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.

A single yearly dose of zoledronic acid had no impact on the progression of abdominal aortic calcification in postmenopausal women with osteoporosis, based on data from 502 women.

Although bisphosphonates have been shown to reduce the formation and progression of vascular calcification in animal studies, the impact on aortic calcification in humans has not been studied, wrote Guoqi Cai, PhD, of the University of Tasmania, Australia, and colleagues.

In a post hoc analysis published in Osteoporosis International, the researchers reviewed data from the HORIZON Pivotal Fracture trial of women with osteoporosis.

The study population included 234 postmenopausal women with osteoporosis who received an annual infusion of 5 mg zoledronic acid (ZA) and 268 who received a placebo. The mean age of the women was 72.5 years. Overall, abdominal aortic calcification (AAC) was present in 292 women (58%) at baseline, defined as an AAC score greater than 0, and AAC scores were similar between the intervention and placebo groups.

Over 3 years, AAC progressed similarly between the ZA and placebo groups (29% and 31%, respectively). Progression was defined as an increase in AAC score, which was measured by comparing spinal x-rays at baseline and after 3 years. In a subgroup analysis, progression of AAC was similar between the ZA and placebo groups with and without baseline AAC.

“The lack of effect on the progression of vascular calcification with zoledronic acid treatment in this study does not rule out a potential role of bisphosphonates in reducing cardiovascular mortality mediated through other mechanisms,” the researchers noted.

No correlation appeared between change in AAC score and change in bone mineral density at the total hip and femoral neck during the study period in any of the groups.

The study findings were limited by several factors including the post hoc analysis, potential lack of sensitivity of the AAC-8 scale in measuring small AAC changes, and homogenous study population, the researchers noted.

However, the study is the first to examine the impact of zoledronic acid on aortic calcification in humans, and was strengthened by the randomized design, the researchers said. Although other studies on the impact of bisphosphonates on vascular calcification have been inconsistent, the “finding that zoledronic acid was not protective against vascular calcification agrees with previous trials of nitrogen-containing bisphosphonates conducted in postmenopausal women with osteoporosis,” as well as chronic kidney disease patients and renal transplant patients, they said.

“Thus, our findings do not support the use of zoledronic acid for the treatment of vascular calcification,” they concluded.

The study was supported by Novartis. Dr. Cai had no financial conflicts to disclose.

[email protected]

SOURCE: Cai G. et al. Osteoporosis Int. 2020 May 2. doi: 10.1007/s00198-020-05430-z.