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Does daily inhaler monitoring improve asthma outcomes in children?
Among children with moderate or severe persistent asthma, a randomized trial suggests.
But the intervention also may lead to more ED visits and increased hospitalization rates.
“We improved asthma symptom control but did not reduce health care use,” Ruchi S. Gupta, MD, MPH, and colleagues, wrote in a study published in Pediatrics.
The monitoring system alerted clinicians when a patient used a short-acting beta-agonist more than four times in a day. It could be that the “alerts enabled providers to detect asthma exacerbation virtually and refer for clinically appropriate care that included directing children to the ED,” the authors suggested. It also is possible that the intervention led caregivers to be more vigilant about symptoms and more empowered to seek care.
Adherence to preventive regimens
Many patients with asthma need to use preventive medications such as daily inhaled corticosteroids to control symptoms. Researchers have developed sensor-based inhaler monitoring interventions to improve treatment adherence, but the effectiveness of these interventions in improving asthma outcomes in urban and minority populations is unclear.
To assess the effectiveness of a clinically integrated, sensor-based inhaler monitoring intervention on improving asthma symptom control and related outcomes in children, Dr. Gupta, of Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted a randomized, unblinded study, known as the Improving Technology-Assisted Recording of Asthma Control in Children (iTRACC) trial. They included 252 children: 127 in the control group and 125 in the intervention group.
Patients in the intervention group received Propeller Health’s Food and Drug Administration–cleared inhaler sensors for inhaled corticosteroids and short-acting beta-agonists. Caregivers could use a mobile application and clinicians could use a Web portal to track patients’ medication use. The app featured personalized insights, educational content, encouragement, surveys, and care team services.
Researchers recruited caregivers and children from five Chicago clinics for the study, which was conducted between 2016 and 2018. They included children aged 4-17 years who had a prescription for daily inhaled corticosteroids for at least 1 year before enrollment. In addition, participants had at least 1 exacerbation requiring oral corticosteroids in the previous year. They excluded children with other respiratory conditions. They also excluded participants who did not speak English because the app was available only in English.
“Sensors monitored inhaled medication use, capturing the date, time, and number of uses, and transmitted this information via Bluetooth to a paired smartphone and the provider portal in real-time,” the authors said.
Clinicians were alerted to call participants if a patient missed inhaled corticosteroid doses for 4 continuous days or used more than 4 short-acting beta-agonist doses per day. Clinicians could help guide asthma management, schedule an appointment, refill medications, and address technical difficulties with the sensors.
The intervention and control groups had similar baseline characteristics. About one-third of the patients were female, and the mean age was 9.3 years. In the control group, 28% identified as Hispanic, and 33% identified as non-Hispanic Black. In the intervention group, 40% identified as Hispanic, and 23% identified as non-Hispanic Black. About 59% reported Medicaid insurance. The intervention and control arms completed electronic surveys at 1, 3, 6, 9, and 12 months.
Average Asthma Control Test score increased from 19 to 22 in the intervention group, compared with an increase from 19 to 20 in the control group. Adjusted rates of emergency department visits and hospitalizations were greater in the intervention group (incidence rate ratios, 2.2 and 3.4, respectively). A measure of caregiver quality of life was greater in the intervention group, although the difference was not significant.
During the trial, more caregivers in the intervention group reported asthma attacks for which steroids were prescribed by a medical office (73% vs. 35%).
Some participants had to manually enter the number of daily puffs into the app because their inhalers were incompatible with the sensors. In addition, some data were missing because of incomplete or missing survey responses and sensor failure over time. “The number of intervention participants with actively transmitting sensors decreased from 102 at baseline to 56 at 12 months,” Dr. Gupta and associates noted.
Important area of research
“One interesting finding of this study is the increase in health care use in the intervention group to nearly twice as many emergency department (ED) visits and three times as many hospitalizations as the control group over 12 months,” Rachelle R. Ramsey, PhD, and Theresa W. Guilbert, MD, MS, of the University of Cincinnati, wrote in a related commentary. “Although it is plausible that, as the authors suggest, greater asthma knowledge and monitoring may have led to increased vigilance of asthma symptoms, it seems that this would have only led to an increase in ED visits but not hospitalizations.”
The mixture of objective electronic monitoring and subjective self-reported adherence may complicate interpretation of the results, they added.
“Overall, this article underscores the feasibility and importance of sensor-based electronic monitoring of adherence in pediatric asthma and encourages future research in this area,” Dr. Ramsey and Dr. Guilbert said.
The trial was supported by the UnitedHealth Group. Dr. Gupta has received grants from the National Institutes of Health, Rho, and other organizations, and has served as a medical consultant and adviser for a variety of companies. Dr. Ramsey is supported by the NIH. Dr. Guilbert reported fees from the American Board of Pediatrics, the Pediatric Pulmonary Subboard, and some pharmaceutical companies, plus grants from the NIH, grants and personal fees from Sanofi, Regeneron, and AstraZeneca, and royalties from UpToDate.
SOURCE: Gupta RS et al. Pediatrics. 2020 Dec 22. doi: 10.1542/peds.2020-1330.
Among children with moderate or severe persistent asthma, a randomized trial suggests.
But the intervention also may lead to more ED visits and increased hospitalization rates.
“We improved asthma symptom control but did not reduce health care use,” Ruchi S. Gupta, MD, MPH, and colleagues, wrote in a study published in Pediatrics.
The monitoring system alerted clinicians when a patient used a short-acting beta-agonist more than four times in a day. It could be that the “alerts enabled providers to detect asthma exacerbation virtually and refer for clinically appropriate care that included directing children to the ED,” the authors suggested. It also is possible that the intervention led caregivers to be more vigilant about symptoms and more empowered to seek care.
Adherence to preventive regimens
Many patients with asthma need to use preventive medications such as daily inhaled corticosteroids to control symptoms. Researchers have developed sensor-based inhaler monitoring interventions to improve treatment adherence, but the effectiveness of these interventions in improving asthma outcomes in urban and minority populations is unclear.
To assess the effectiveness of a clinically integrated, sensor-based inhaler monitoring intervention on improving asthma symptom control and related outcomes in children, Dr. Gupta, of Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted a randomized, unblinded study, known as the Improving Technology-Assisted Recording of Asthma Control in Children (iTRACC) trial. They included 252 children: 127 in the control group and 125 in the intervention group.
Patients in the intervention group received Propeller Health’s Food and Drug Administration–cleared inhaler sensors for inhaled corticosteroids and short-acting beta-agonists. Caregivers could use a mobile application and clinicians could use a Web portal to track patients’ medication use. The app featured personalized insights, educational content, encouragement, surveys, and care team services.
Researchers recruited caregivers and children from five Chicago clinics for the study, which was conducted between 2016 and 2018. They included children aged 4-17 years who had a prescription for daily inhaled corticosteroids for at least 1 year before enrollment. In addition, participants had at least 1 exacerbation requiring oral corticosteroids in the previous year. They excluded children with other respiratory conditions. They also excluded participants who did not speak English because the app was available only in English.
“Sensors monitored inhaled medication use, capturing the date, time, and number of uses, and transmitted this information via Bluetooth to a paired smartphone and the provider portal in real-time,” the authors said.
Clinicians were alerted to call participants if a patient missed inhaled corticosteroid doses for 4 continuous days or used more than 4 short-acting beta-agonist doses per day. Clinicians could help guide asthma management, schedule an appointment, refill medications, and address technical difficulties with the sensors.
The intervention and control groups had similar baseline characteristics. About one-third of the patients were female, and the mean age was 9.3 years. In the control group, 28% identified as Hispanic, and 33% identified as non-Hispanic Black. In the intervention group, 40% identified as Hispanic, and 23% identified as non-Hispanic Black. About 59% reported Medicaid insurance. The intervention and control arms completed electronic surveys at 1, 3, 6, 9, and 12 months.
Average Asthma Control Test score increased from 19 to 22 in the intervention group, compared with an increase from 19 to 20 in the control group. Adjusted rates of emergency department visits and hospitalizations were greater in the intervention group (incidence rate ratios, 2.2 and 3.4, respectively). A measure of caregiver quality of life was greater in the intervention group, although the difference was not significant.
During the trial, more caregivers in the intervention group reported asthma attacks for which steroids were prescribed by a medical office (73% vs. 35%).
Some participants had to manually enter the number of daily puffs into the app because their inhalers were incompatible with the sensors. In addition, some data were missing because of incomplete or missing survey responses and sensor failure over time. “The number of intervention participants with actively transmitting sensors decreased from 102 at baseline to 56 at 12 months,” Dr. Gupta and associates noted.
Important area of research
“One interesting finding of this study is the increase in health care use in the intervention group to nearly twice as many emergency department (ED) visits and three times as many hospitalizations as the control group over 12 months,” Rachelle R. Ramsey, PhD, and Theresa W. Guilbert, MD, MS, of the University of Cincinnati, wrote in a related commentary. “Although it is plausible that, as the authors suggest, greater asthma knowledge and monitoring may have led to increased vigilance of asthma symptoms, it seems that this would have only led to an increase in ED visits but not hospitalizations.”
The mixture of objective electronic monitoring and subjective self-reported adherence may complicate interpretation of the results, they added.
“Overall, this article underscores the feasibility and importance of sensor-based electronic monitoring of adherence in pediatric asthma and encourages future research in this area,” Dr. Ramsey and Dr. Guilbert said.
The trial was supported by the UnitedHealth Group. Dr. Gupta has received grants from the National Institutes of Health, Rho, and other organizations, and has served as a medical consultant and adviser for a variety of companies. Dr. Ramsey is supported by the NIH. Dr. Guilbert reported fees from the American Board of Pediatrics, the Pediatric Pulmonary Subboard, and some pharmaceutical companies, plus grants from the NIH, grants and personal fees from Sanofi, Regeneron, and AstraZeneca, and royalties from UpToDate.
SOURCE: Gupta RS et al. Pediatrics. 2020 Dec 22. doi: 10.1542/peds.2020-1330.
Among children with moderate or severe persistent asthma, a randomized trial suggests.
But the intervention also may lead to more ED visits and increased hospitalization rates.
“We improved asthma symptom control but did not reduce health care use,” Ruchi S. Gupta, MD, MPH, and colleagues, wrote in a study published in Pediatrics.
The monitoring system alerted clinicians when a patient used a short-acting beta-agonist more than four times in a day. It could be that the “alerts enabled providers to detect asthma exacerbation virtually and refer for clinically appropriate care that included directing children to the ED,” the authors suggested. It also is possible that the intervention led caregivers to be more vigilant about symptoms and more empowered to seek care.
Adherence to preventive regimens
Many patients with asthma need to use preventive medications such as daily inhaled corticosteroids to control symptoms. Researchers have developed sensor-based inhaler monitoring interventions to improve treatment adherence, but the effectiveness of these interventions in improving asthma outcomes in urban and minority populations is unclear.
To assess the effectiveness of a clinically integrated, sensor-based inhaler monitoring intervention on improving asthma symptom control and related outcomes in children, Dr. Gupta, of Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted a randomized, unblinded study, known as the Improving Technology-Assisted Recording of Asthma Control in Children (iTRACC) trial. They included 252 children: 127 in the control group and 125 in the intervention group.
Patients in the intervention group received Propeller Health’s Food and Drug Administration–cleared inhaler sensors for inhaled corticosteroids and short-acting beta-agonists. Caregivers could use a mobile application and clinicians could use a Web portal to track patients’ medication use. The app featured personalized insights, educational content, encouragement, surveys, and care team services.
Researchers recruited caregivers and children from five Chicago clinics for the study, which was conducted between 2016 and 2018. They included children aged 4-17 years who had a prescription for daily inhaled corticosteroids for at least 1 year before enrollment. In addition, participants had at least 1 exacerbation requiring oral corticosteroids in the previous year. They excluded children with other respiratory conditions. They also excluded participants who did not speak English because the app was available only in English.
“Sensors monitored inhaled medication use, capturing the date, time, and number of uses, and transmitted this information via Bluetooth to a paired smartphone and the provider portal in real-time,” the authors said.
Clinicians were alerted to call participants if a patient missed inhaled corticosteroid doses for 4 continuous days or used more than 4 short-acting beta-agonist doses per day. Clinicians could help guide asthma management, schedule an appointment, refill medications, and address technical difficulties with the sensors.
The intervention and control groups had similar baseline characteristics. About one-third of the patients were female, and the mean age was 9.3 years. In the control group, 28% identified as Hispanic, and 33% identified as non-Hispanic Black. In the intervention group, 40% identified as Hispanic, and 23% identified as non-Hispanic Black. About 59% reported Medicaid insurance. The intervention and control arms completed electronic surveys at 1, 3, 6, 9, and 12 months.
Average Asthma Control Test score increased from 19 to 22 in the intervention group, compared with an increase from 19 to 20 in the control group. Adjusted rates of emergency department visits and hospitalizations were greater in the intervention group (incidence rate ratios, 2.2 and 3.4, respectively). A measure of caregiver quality of life was greater in the intervention group, although the difference was not significant.
During the trial, more caregivers in the intervention group reported asthma attacks for which steroids were prescribed by a medical office (73% vs. 35%).
Some participants had to manually enter the number of daily puffs into the app because their inhalers were incompatible with the sensors. In addition, some data were missing because of incomplete or missing survey responses and sensor failure over time. “The number of intervention participants with actively transmitting sensors decreased from 102 at baseline to 56 at 12 months,” Dr. Gupta and associates noted.
Important area of research
“One interesting finding of this study is the increase in health care use in the intervention group to nearly twice as many emergency department (ED) visits and three times as many hospitalizations as the control group over 12 months,” Rachelle R. Ramsey, PhD, and Theresa W. Guilbert, MD, MS, of the University of Cincinnati, wrote in a related commentary. “Although it is plausible that, as the authors suggest, greater asthma knowledge and monitoring may have led to increased vigilance of asthma symptoms, it seems that this would have only led to an increase in ED visits but not hospitalizations.”
The mixture of objective electronic monitoring and subjective self-reported adherence may complicate interpretation of the results, they added.
“Overall, this article underscores the feasibility and importance of sensor-based electronic monitoring of adherence in pediatric asthma and encourages future research in this area,” Dr. Ramsey and Dr. Guilbert said.
The trial was supported by the UnitedHealth Group. Dr. Gupta has received grants from the National Institutes of Health, Rho, and other organizations, and has served as a medical consultant and adviser for a variety of companies. Dr. Ramsey is supported by the NIH. Dr. Guilbert reported fees from the American Board of Pediatrics, the Pediatric Pulmonary Subboard, and some pharmaceutical companies, plus grants from the NIH, grants and personal fees from Sanofi, Regeneron, and AstraZeneca, and royalties from UpToDate.
SOURCE: Gupta RS et al. Pediatrics. 2020 Dec 22. doi: 10.1542/peds.2020-1330.
FROM PEDIATRICS
Pregnant women using substances need support
according to a panel of experts speaking at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. The panelists highlighted several key issues for addressing alcohol, opioids, and cannabis use by pregnant women.
No amount of alcohol is safe
Many women believe that a limited amount of alcohol is safe during pregnancy, in part because of mixed messages in the media suggesting that light drinking is okay, according to Erin Tracy Bradley, MD, MPH, of Massachusetts General Hospital, Boston.
“We need to do a better job teaching our patients about the potential dangers of alcohol,” Dr. Bradley said in her presentation.
In fact, data suggest that women more at risk for an alcohol-exposed pregnancy are older and better educated. Dr. Bradley described the pattern of malformation for fetal alcohol syndrome (FAS) that includes small eyes, a thin upper lip, and smooth skin between the upper lip and nose.
“The only cause we know of [for FAS] is alcohol exposure intrauterine for the fetus,” so it is preventable with counseling and care, and thought to be the leading preventable cause of birth defects during pregnancies, she said.
The bottom line is that there is no safe amount of alcohol,” said Dr. Bradley. However, providers are inconsistent in discussing alcohol with their pregnant patients. In addition, universal screening is important because it is difficult to predict which women will be drinking during pregnancy.
Screening allows providers to quickly assess the severity of substance use, offer a brief intervention to raise patient awareness, and refer if necessary. “There should be ‘absolutely no judgment, no shame, no stigma,’ ” Dr. Bradley emphasized. “We are the patient’s partners, and we are trying to help them have a healthy pregnancy. “
Opioid use in pregnancy spiked in recent decades
“Women have always been overrepresented when opioids are involved,” said Tricia E. Wright, MD, of the University of California, San Francisco.
Long-term studies have shown that, overall, women are more likely to be given opioids and given higher doses, compared with men, often for conditions in which opioids are not effective, she noted.
Women use substances differently than men; “they use them to cope with everyday life,” and a history of interpersonal violence and sexual assault are coming among women with opioid use disorders, said Dr. Wright.
The majority of women with opioid use disorders are of childbearing age, which has led to an increase in neonatal abstinence syndrome (NAS) said Dr. Wright.
She cited 2014 data from the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report showing an increase in NAS from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1,000 hospital births in 2012. This increase has led to “misguided” efforts to prevent NAS through opioid detoxification, Dr. Wright said. She and colleagues conducted a systematic review in 2018 and found that, in fact, the evidence does not support detoxification as a recommended treatment intervention during pregnancy.
Opioid agonist therapy has multiple benefits for both the mother and fetus, Dr. Wright said. Maternal benefits include reduction in overdose-related deaths; decrease in the risk of HIV, hepatitis B, and hepatitis C; and increased engagement in prenatal care and recovery treatment. Fetal benefits include reduced fetal stress with the reduced fluctuations in maternal opioid levels, as well as decreases in intrauterine fetal death, intrauterine growth restriction, and preterm delivery.
“We know that relapse kills” because patients lose their tolerance, Dr. Wright said. “What we have seen is that overdose deaths are a leading cause of death in the postpartum period.”
When it comes to treatment, both methadone and buprenorphine are safe and effective options in pregnancy, she said. Treatment decisions should be made based on available options, patient preference, and a patient’s previous treatment experiences, as well as disease severity, social support, and the intensity of treatment needed.
“Whatever medicine you choose, it takes a village to coordinate the care,” Dr. Wright said. Maternal dose has no effect on neonatal withdrawal, so women should be encouraged to report any concerns. Either medication is compatible with breastfeeding. In fact, breastfeeding has many benefits in preventing neonatal withdrawal syndrome. Smoking cessation should be encouraged because it improves neonatal withdrawal.
Minimizing stigma is paramount, said Dr. Wright. “Substance use disorders are among the most stigmatized medical conditions, and pregnant women with substance use disorders are even more stigmatized.”
Clinicians can support patients by focusing on appropriate language, patients aren’t “addicts,” they are people with an opioid use disorder, she said.
Compassionate care for cannabis users
Cannabis use has a long history of association with women’s health, said Mishka Terplan, MD, MPH, of Friends Research Institute, Baltimore. Although cannabis use overall has increased steadily in recent years, data indicate that people who are pregnant are less likely to use cannabis than those who aren’t. The exception is that individuals who report using cannabis for medical purposes only remain consistent cannabis users during pregnancy.
“The concern is cannabis and birth outcomes, as well as developmental outcomes,” Dr. Terplan said. Multiple studies on this topic support several systematic reviews, and “depending on which decade you read, the results differ slightly.”
Reviews from the 1990s showed little to no effect on birth weight, but more recent studies, such as a meta-analysis published in BMJ Open in 2015, showed increased risk of neonatal outcomes such as low birth weight, anemia, and odds of admission to the neonatal ICU.
“The difference in these two eras is thought to be caused by the change in the definition of what cannabis is, and the potency has increased, and possibly therefore, as a consequence, we see outcomes we hadn’t seen before,” Dr. Terplan explained.
There is a concern with increased use and increased legalization that, there could be adverse effects on neonatal health, but recent studies in Colorado do not show a significant difference in neonatal outcomes before and after legalization, he said.
Data from pregnant women suggest that with regard to cannabis, they are concerned about their health, but they tend to seek information about cannabis use in pregnancy from family, friends, and the Internet rather than their health providers, said Dr. Terplan.
However, studies also show that providers tend to fall short and do a poor job of talking to pregnant patients about cannabis. When providers do discuss cannabis, they tend to focus on the legal aspects. “We are failing our patients when it comes to cannabis,” Dr. Terplan said. “We don’t provide the information and support they need and desire.” Instead, many providers “deploy urine drug testing, which we misinterpret.”
Dr. Terplan explained that point-of-care cannabis testing that shows “THC” is not measuring tetrahydrocannabinol, the psychoactive compound; rather it captures the nonpsychoactive metabolite of THC, one that sticks around for a long time in the biological compartment.
Dr. Terplan urged clinicians not to use urine tests as a default indicator of cannabis use, but instead, “we need to sit, listen, and work with our patients from a place of empathy.”
Questions answered
During a question-and-answer session following the panel, Dr. Bradley was asked about preconception counseling related to alcohol consumption.
“Preconception time is a perfect time to do screening, or offer contraception if a patient is a place where she doesn’t want to become pregnant or if she wants to take advantage of any therapeutic options to get well prior to pregnancy,” she said.
Dr. Wright responded to a question about the impact of punitive actions such as drug testing and incarceration. “These things decrease the chance that patients will get adequate prenatal care,” she said. “We need to advocate for our patients and advocate for changing drug laws.”
Dr. Terplan responded to a question about the impact of substance use on parenting. Parents use nicotine, alcohol, and also cannabis, he said. Data showing an association between substance use and cases of child abuse and neglect, “are of poor quality and do not support this association.”
Overall, “we need to have consistent messaging that we are not there to judge patients,” Dr. Bradley added. “The last thing we want is for patients not to be honest with us.”
Dr. Wright disclosed consulting fees from McKesson and royalties as the coauthor of a book, “Opioid-Use Disorders in Pregnancy.” Dr. Bradley had no financial conflicts to disclose. Dr. Terplan had no financial conflicts to disclose.
according to a panel of experts speaking at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. The panelists highlighted several key issues for addressing alcohol, opioids, and cannabis use by pregnant women.
No amount of alcohol is safe
Many women believe that a limited amount of alcohol is safe during pregnancy, in part because of mixed messages in the media suggesting that light drinking is okay, according to Erin Tracy Bradley, MD, MPH, of Massachusetts General Hospital, Boston.
“We need to do a better job teaching our patients about the potential dangers of alcohol,” Dr. Bradley said in her presentation.
In fact, data suggest that women more at risk for an alcohol-exposed pregnancy are older and better educated. Dr. Bradley described the pattern of malformation for fetal alcohol syndrome (FAS) that includes small eyes, a thin upper lip, and smooth skin between the upper lip and nose.
“The only cause we know of [for FAS] is alcohol exposure intrauterine for the fetus,” so it is preventable with counseling and care, and thought to be the leading preventable cause of birth defects during pregnancies, she said.
The bottom line is that there is no safe amount of alcohol,” said Dr. Bradley. However, providers are inconsistent in discussing alcohol with their pregnant patients. In addition, universal screening is important because it is difficult to predict which women will be drinking during pregnancy.
Screening allows providers to quickly assess the severity of substance use, offer a brief intervention to raise patient awareness, and refer if necessary. “There should be ‘absolutely no judgment, no shame, no stigma,’ ” Dr. Bradley emphasized. “We are the patient’s partners, and we are trying to help them have a healthy pregnancy. “
Opioid use in pregnancy spiked in recent decades
“Women have always been overrepresented when opioids are involved,” said Tricia E. Wright, MD, of the University of California, San Francisco.
Long-term studies have shown that, overall, women are more likely to be given opioids and given higher doses, compared with men, often for conditions in which opioids are not effective, she noted.
Women use substances differently than men; “they use them to cope with everyday life,” and a history of interpersonal violence and sexual assault are coming among women with opioid use disorders, said Dr. Wright.
The majority of women with opioid use disorders are of childbearing age, which has led to an increase in neonatal abstinence syndrome (NAS) said Dr. Wright.
She cited 2014 data from the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report showing an increase in NAS from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1,000 hospital births in 2012. This increase has led to “misguided” efforts to prevent NAS through opioid detoxification, Dr. Wright said. She and colleagues conducted a systematic review in 2018 and found that, in fact, the evidence does not support detoxification as a recommended treatment intervention during pregnancy.
Opioid agonist therapy has multiple benefits for both the mother and fetus, Dr. Wright said. Maternal benefits include reduction in overdose-related deaths; decrease in the risk of HIV, hepatitis B, and hepatitis C; and increased engagement in prenatal care and recovery treatment. Fetal benefits include reduced fetal stress with the reduced fluctuations in maternal opioid levels, as well as decreases in intrauterine fetal death, intrauterine growth restriction, and preterm delivery.
“We know that relapse kills” because patients lose their tolerance, Dr. Wright said. “What we have seen is that overdose deaths are a leading cause of death in the postpartum period.”
When it comes to treatment, both methadone and buprenorphine are safe and effective options in pregnancy, she said. Treatment decisions should be made based on available options, patient preference, and a patient’s previous treatment experiences, as well as disease severity, social support, and the intensity of treatment needed.
“Whatever medicine you choose, it takes a village to coordinate the care,” Dr. Wright said. Maternal dose has no effect on neonatal withdrawal, so women should be encouraged to report any concerns. Either medication is compatible with breastfeeding. In fact, breastfeeding has many benefits in preventing neonatal withdrawal syndrome. Smoking cessation should be encouraged because it improves neonatal withdrawal.
Minimizing stigma is paramount, said Dr. Wright. “Substance use disorders are among the most stigmatized medical conditions, and pregnant women with substance use disorders are even more stigmatized.”
Clinicians can support patients by focusing on appropriate language, patients aren’t “addicts,” they are people with an opioid use disorder, she said.
Compassionate care for cannabis users
Cannabis use has a long history of association with women’s health, said Mishka Terplan, MD, MPH, of Friends Research Institute, Baltimore. Although cannabis use overall has increased steadily in recent years, data indicate that people who are pregnant are less likely to use cannabis than those who aren’t. The exception is that individuals who report using cannabis for medical purposes only remain consistent cannabis users during pregnancy.
“The concern is cannabis and birth outcomes, as well as developmental outcomes,” Dr. Terplan said. Multiple studies on this topic support several systematic reviews, and “depending on which decade you read, the results differ slightly.”
Reviews from the 1990s showed little to no effect on birth weight, but more recent studies, such as a meta-analysis published in BMJ Open in 2015, showed increased risk of neonatal outcomes such as low birth weight, anemia, and odds of admission to the neonatal ICU.
“The difference in these two eras is thought to be caused by the change in the definition of what cannabis is, and the potency has increased, and possibly therefore, as a consequence, we see outcomes we hadn’t seen before,” Dr. Terplan explained.
There is a concern with increased use and increased legalization that, there could be adverse effects on neonatal health, but recent studies in Colorado do not show a significant difference in neonatal outcomes before and after legalization, he said.
Data from pregnant women suggest that with regard to cannabis, they are concerned about their health, but they tend to seek information about cannabis use in pregnancy from family, friends, and the Internet rather than their health providers, said Dr. Terplan.
However, studies also show that providers tend to fall short and do a poor job of talking to pregnant patients about cannabis. When providers do discuss cannabis, they tend to focus on the legal aspects. “We are failing our patients when it comes to cannabis,” Dr. Terplan said. “We don’t provide the information and support they need and desire.” Instead, many providers “deploy urine drug testing, which we misinterpret.”
Dr. Terplan explained that point-of-care cannabis testing that shows “THC” is not measuring tetrahydrocannabinol, the psychoactive compound; rather it captures the nonpsychoactive metabolite of THC, one that sticks around for a long time in the biological compartment.
Dr. Terplan urged clinicians not to use urine tests as a default indicator of cannabis use, but instead, “we need to sit, listen, and work with our patients from a place of empathy.”
Questions answered
During a question-and-answer session following the panel, Dr. Bradley was asked about preconception counseling related to alcohol consumption.
“Preconception time is a perfect time to do screening, or offer contraception if a patient is a place where she doesn’t want to become pregnant or if she wants to take advantage of any therapeutic options to get well prior to pregnancy,” she said.
Dr. Wright responded to a question about the impact of punitive actions such as drug testing and incarceration. “These things decrease the chance that patients will get adequate prenatal care,” she said. “We need to advocate for our patients and advocate for changing drug laws.”
Dr. Terplan responded to a question about the impact of substance use on parenting. Parents use nicotine, alcohol, and also cannabis, he said. Data showing an association between substance use and cases of child abuse and neglect, “are of poor quality and do not support this association.”
Overall, “we need to have consistent messaging that we are not there to judge patients,” Dr. Bradley added. “The last thing we want is for patients not to be honest with us.”
Dr. Wright disclosed consulting fees from McKesson and royalties as the coauthor of a book, “Opioid-Use Disorders in Pregnancy.” Dr. Bradley had no financial conflicts to disclose. Dr. Terplan had no financial conflicts to disclose.
according to a panel of experts speaking at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists. The panelists highlighted several key issues for addressing alcohol, opioids, and cannabis use by pregnant women.
No amount of alcohol is safe
Many women believe that a limited amount of alcohol is safe during pregnancy, in part because of mixed messages in the media suggesting that light drinking is okay, according to Erin Tracy Bradley, MD, MPH, of Massachusetts General Hospital, Boston.
“We need to do a better job teaching our patients about the potential dangers of alcohol,” Dr. Bradley said in her presentation.
In fact, data suggest that women more at risk for an alcohol-exposed pregnancy are older and better educated. Dr. Bradley described the pattern of malformation for fetal alcohol syndrome (FAS) that includes small eyes, a thin upper lip, and smooth skin between the upper lip and nose.
“The only cause we know of [for FAS] is alcohol exposure intrauterine for the fetus,” so it is preventable with counseling and care, and thought to be the leading preventable cause of birth defects during pregnancies, she said.
The bottom line is that there is no safe amount of alcohol,” said Dr. Bradley. However, providers are inconsistent in discussing alcohol with their pregnant patients. In addition, universal screening is important because it is difficult to predict which women will be drinking during pregnancy.
Screening allows providers to quickly assess the severity of substance use, offer a brief intervention to raise patient awareness, and refer if necessary. “There should be ‘absolutely no judgment, no shame, no stigma,’ ” Dr. Bradley emphasized. “We are the patient’s partners, and we are trying to help them have a healthy pregnancy. “
Opioid use in pregnancy spiked in recent decades
“Women have always been overrepresented when opioids are involved,” said Tricia E. Wright, MD, of the University of California, San Francisco.
Long-term studies have shown that, overall, women are more likely to be given opioids and given higher doses, compared with men, often for conditions in which opioids are not effective, she noted.
Women use substances differently than men; “they use them to cope with everyday life,” and a history of interpersonal violence and sexual assault are coming among women with opioid use disorders, said Dr. Wright.
The majority of women with opioid use disorders are of childbearing age, which has led to an increase in neonatal abstinence syndrome (NAS) said Dr. Wright.
She cited 2014 data from the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report showing an increase in NAS from 1.2 per 1,000 hospital births in 2000 to 5.8 per 1,000 hospital births in 2012. This increase has led to “misguided” efforts to prevent NAS through opioid detoxification, Dr. Wright said. She and colleagues conducted a systematic review in 2018 and found that, in fact, the evidence does not support detoxification as a recommended treatment intervention during pregnancy.
Opioid agonist therapy has multiple benefits for both the mother and fetus, Dr. Wright said. Maternal benefits include reduction in overdose-related deaths; decrease in the risk of HIV, hepatitis B, and hepatitis C; and increased engagement in prenatal care and recovery treatment. Fetal benefits include reduced fetal stress with the reduced fluctuations in maternal opioid levels, as well as decreases in intrauterine fetal death, intrauterine growth restriction, and preterm delivery.
“We know that relapse kills” because patients lose their tolerance, Dr. Wright said. “What we have seen is that overdose deaths are a leading cause of death in the postpartum period.”
When it comes to treatment, both methadone and buprenorphine are safe and effective options in pregnancy, she said. Treatment decisions should be made based on available options, patient preference, and a patient’s previous treatment experiences, as well as disease severity, social support, and the intensity of treatment needed.
“Whatever medicine you choose, it takes a village to coordinate the care,” Dr. Wright said. Maternal dose has no effect on neonatal withdrawal, so women should be encouraged to report any concerns. Either medication is compatible with breastfeeding. In fact, breastfeeding has many benefits in preventing neonatal withdrawal syndrome. Smoking cessation should be encouraged because it improves neonatal withdrawal.
Minimizing stigma is paramount, said Dr. Wright. “Substance use disorders are among the most stigmatized medical conditions, and pregnant women with substance use disorders are even more stigmatized.”
Clinicians can support patients by focusing on appropriate language, patients aren’t “addicts,” they are people with an opioid use disorder, she said.
Compassionate care for cannabis users
Cannabis use has a long history of association with women’s health, said Mishka Terplan, MD, MPH, of Friends Research Institute, Baltimore. Although cannabis use overall has increased steadily in recent years, data indicate that people who are pregnant are less likely to use cannabis than those who aren’t. The exception is that individuals who report using cannabis for medical purposes only remain consistent cannabis users during pregnancy.
“The concern is cannabis and birth outcomes, as well as developmental outcomes,” Dr. Terplan said. Multiple studies on this topic support several systematic reviews, and “depending on which decade you read, the results differ slightly.”
Reviews from the 1990s showed little to no effect on birth weight, but more recent studies, such as a meta-analysis published in BMJ Open in 2015, showed increased risk of neonatal outcomes such as low birth weight, anemia, and odds of admission to the neonatal ICU.
“The difference in these two eras is thought to be caused by the change in the definition of what cannabis is, and the potency has increased, and possibly therefore, as a consequence, we see outcomes we hadn’t seen before,” Dr. Terplan explained.
There is a concern with increased use and increased legalization that, there could be adverse effects on neonatal health, but recent studies in Colorado do not show a significant difference in neonatal outcomes before and after legalization, he said.
Data from pregnant women suggest that with regard to cannabis, they are concerned about their health, but they tend to seek information about cannabis use in pregnancy from family, friends, and the Internet rather than their health providers, said Dr. Terplan.
However, studies also show that providers tend to fall short and do a poor job of talking to pregnant patients about cannabis. When providers do discuss cannabis, they tend to focus on the legal aspects. “We are failing our patients when it comes to cannabis,” Dr. Terplan said. “We don’t provide the information and support they need and desire.” Instead, many providers “deploy urine drug testing, which we misinterpret.”
Dr. Terplan explained that point-of-care cannabis testing that shows “THC” is not measuring tetrahydrocannabinol, the psychoactive compound; rather it captures the nonpsychoactive metabolite of THC, one that sticks around for a long time in the biological compartment.
Dr. Terplan urged clinicians not to use urine tests as a default indicator of cannabis use, but instead, “we need to sit, listen, and work with our patients from a place of empathy.”
Questions answered
During a question-and-answer session following the panel, Dr. Bradley was asked about preconception counseling related to alcohol consumption.
“Preconception time is a perfect time to do screening, or offer contraception if a patient is a place where she doesn’t want to become pregnant or if she wants to take advantage of any therapeutic options to get well prior to pregnancy,” she said.
Dr. Wright responded to a question about the impact of punitive actions such as drug testing and incarceration. “These things decrease the chance that patients will get adequate prenatal care,” she said. “We need to advocate for our patients and advocate for changing drug laws.”
Dr. Terplan responded to a question about the impact of substance use on parenting. Parents use nicotine, alcohol, and also cannabis, he said. Data showing an association between substance use and cases of child abuse and neglect, “are of poor quality and do not support this association.”
Overall, “we need to have consistent messaging that we are not there to judge patients,” Dr. Bradley added. “The last thing we want is for patients not to be honest with us.”
Dr. Wright disclosed consulting fees from McKesson and royalties as the coauthor of a book, “Opioid-Use Disorders in Pregnancy.” Dr. Bradley had no financial conflicts to disclose. Dr. Terplan had no financial conflicts to disclose.
FROM ACOG 2020
HPV vaccine appears effective for treating warts, particularly in children
The human papillomavirus (HPV) vaccine, recommended by the Centers for Disease Control and Prevention for the prevention of HPV-associated genital warts and neoplasia, appears to be an effective and perhaps underappreciated treatment of existing cutaneous warts, according to expert speaking at the annual Coastal Dermatology symposium, held virtually.
, but a recently published review provides strong evidence that this is a practical clinical strategy, according to Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston.
“Clearly, if you have someone, particularly a youngster, and you’re having trouble getting rid of their warts and they are age 9 years or above – and they need the vaccine anyhow – that’s a win-win proposition,” Dr. Rosen said.
The current nonavalent HPV vaccine is approved for individuals from age 9 to age 45. Although the CDC recommends routine vaccination at age 11 or 12 years, it allows earlier vaccination within the label.
The recently published and updated evidence of a benefit from treatment comes from a systematic literature review. For the review, 63 articles were drawn from the PubMed and Cochrane databases. The studies yielded 4,439 patients with cutaneous warts at the time they received the HPV vaccine or who specifically received vaccine as a treatment strategy.
As has been suggested previously in the case series and in a limited number of prospective studies, the majority of warts, including cutaneous warts and anogenital warts, resolved following vaccine administration.
“Mostly these were common warts, plantar warts, and flat warts,” Dr. Rosen said, but the paper also reported successful treatment of recurrent respiratory papillomatosis, squamous cell carcinomas, and basal cell carcinomas.
Case reports and small studies associating HPV vaccine with successful resolution of warts are easy to find in the literature. For example, 60% of patients achieved a complete response and 30% a partial response to HPV vaccine in one small prospective study of 26 patients with genital warts. Following vaccination, no recurrences were observed after a median follow-up of more than 8 months.
In the review paper, most of the cases involved patients who received the quadrivalent HPV vaccine, Dr. Rosen noted. Only one received the updated nonavalent vaccine, which, in addition to protection against the 6, 11, 16, and 18 subtypes extends protection to subtypes 31, 33, 45, 52, and 58.
“You would expect the nonavalent vaccine to provide the same protection. It is the same vaccine. It just offers activity against more subtypes,” Dr. Rosen said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He reported that he personally has used the nonavalent vaccine successfully to treat a cutaneous wart.
The nonavalent vaccine can be administered in just two doses for those who receive the first dose before age 15. In others, it is given in three doses at 1- to 2-month intervals, according to Dr. Rosen. He said the efficacy for preventing genital warts and most HPV-related neoplasia exceeds 90%, although it is lower for penile and anal cancer. The protection extends for at least 10 years, but he said that he believes that it is likely to be longer.
“The HPV vaccine is really, really safe,” Dr. Rosen said. Besides injection-site reactions, the most common adverse event is syncope. For this reason, patients are advised to stay seated for 30 minutes after administration.
There is some evidence for cross-immunity for HPV subtypes not covered by the vaccine, particularly among children, Dr. Rosen commented. Citing the review article, he said that, although almost all HPV-associated warts resolve in children when treated with the vaccine, response is somewhat lower in adolescents and further reduced in adults.
In an interview, the senior author of the recent literature review, Natasha A. Mesinkovska, MD, PhD, associate professor of dermatology, University of California, Irvine, agreed with Dr. Rosen about the value of HPV vaccine for patients not responding to conventional therapies for HPV-related cutaneous warts.
“I think HPV vaccine is an excellent option for those patients, even older ones at 45 years of age if cost is not an issue,” she said. She did offer a caveat. In a recent statement from the International Papillomavirus Society (IPVS) on a world shortage of HPV vaccine, it was estimated that supplies might be limited for the next 3-5 years.
Given this shortage, “obtaining them currently may prove to be difficult,” she cautioned.
This publication and Global Academy for Medical Education are owned by the same parent company.
The human papillomavirus (HPV) vaccine, recommended by the Centers for Disease Control and Prevention for the prevention of HPV-associated genital warts and neoplasia, appears to be an effective and perhaps underappreciated treatment of existing cutaneous warts, according to expert speaking at the annual Coastal Dermatology symposium, held virtually.
, but a recently published review provides strong evidence that this is a practical clinical strategy, according to Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston.
“Clearly, if you have someone, particularly a youngster, and you’re having trouble getting rid of their warts and they are age 9 years or above – and they need the vaccine anyhow – that’s a win-win proposition,” Dr. Rosen said.
The current nonavalent HPV vaccine is approved for individuals from age 9 to age 45. Although the CDC recommends routine vaccination at age 11 or 12 years, it allows earlier vaccination within the label.
The recently published and updated evidence of a benefit from treatment comes from a systematic literature review. For the review, 63 articles were drawn from the PubMed and Cochrane databases. The studies yielded 4,439 patients with cutaneous warts at the time they received the HPV vaccine or who specifically received vaccine as a treatment strategy.
As has been suggested previously in the case series and in a limited number of prospective studies, the majority of warts, including cutaneous warts and anogenital warts, resolved following vaccine administration.
“Mostly these were common warts, plantar warts, and flat warts,” Dr. Rosen said, but the paper also reported successful treatment of recurrent respiratory papillomatosis, squamous cell carcinomas, and basal cell carcinomas.
Case reports and small studies associating HPV vaccine with successful resolution of warts are easy to find in the literature. For example, 60% of patients achieved a complete response and 30% a partial response to HPV vaccine in one small prospective study of 26 patients with genital warts. Following vaccination, no recurrences were observed after a median follow-up of more than 8 months.
In the review paper, most of the cases involved patients who received the quadrivalent HPV vaccine, Dr. Rosen noted. Only one received the updated nonavalent vaccine, which, in addition to protection against the 6, 11, 16, and 18 subtypes extends protection to subtypes 31, 33, 45, 52, and 58.
“You would expect the nonavalent vaccine to provide the same protection. It is the same vaccine. It just offers activity against more subtypes,” Dr. Rosen said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He reported that he personally has used the nonavalent vaccine successfully to treat a cutaneous wart.
The nonavalent vaccine can be administered in just two doses for those who receive the first dose before age 15. In others, it is given in three doses at 1- to 2-month intervals, according to Dr. Rosen. He said the efficacy for preventing genital warts and most HPV-related neoplasia exceeds 90%, although it is lower for penile and anal cancer. The protection extends for at least 10 years, but he said that he believes that it is likely to be longer.
“The HPV vaccine is really, really safe,” Dr. Rosen said. Besides injection-site reactions, the most common adverse event is syncope. For this reason, patients are advised to stay seated for 30 minutes after administration.
There is some evidence for cross-immunity for HPV subtypes not covered by the vaccine, particularly among children, Dr. Rosen commented. Citing the review article, he said that, although almost all HPV-associated warts resolve in children when treated with the vaccine, response is somewhat lower in adolescents and further reduced in adults.
In an interview, the senior author of the recent literature review, Natasha A. Mesinkovska, MD, PhD, associate professor of dermatology, University of California, Irvine, agreed with Dr. Rosen about the value of HPV vaccine for patients not responding to conventional therapies for HPV-related cutaneous warts.
“I think HPV vaccine is an excellent option for those patients, even older ones at 45 years of age if cost is not an issue,” she said. She did offer a caveat. In a recent statement from the International Papillomavirus Society (IPVS) on a world shortage of HPV vaccine, it was estimated that supplies might be limited for the next 3-5 years.
Given this shortage, “obtaining them currently may prove to be difficult,” she cautioned.
This publication and Global Academy for Medical Education are owned by the same parent company.
The human papillomavirus (HPV) vaccine, recommended by the Centers for Disease Control and Prevention for the prevention of HPV-associated genital warts and neoplasia, appears to be an effective and perhaps underappreciated treatment of existing cutaneous warts, according to expert speaking at the annual Coastal Dermatology symposium, held virtually.
, but a recently published review provides strong evidence that this is a practical clinical strategy, according to Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston.
“Clearly, if you have someone, particularly a youngster, and you’re having trouble getting rid of their warts and they are age 9 years or above – and they need the vaccine anyhow – that’s a win-win proposition,” Dr. Rosen said.
The current nonavalent HPV vaccine is approved for individuals from age 9 to age 45. Although the CDC recommends routine vaccination at age 11 or 12 years, it allows earlier vaccination within the label.
The recently published and updated evidence of a benefit from treatment comes from a systematic literature review. For the review, 63 articles were drawn from the PubMed and Cochrane databases. The studies yielded 4,439 patients with cutaneous warts at the time they received the HPV vaccine or who specifically received vaccine as a treatment strategy.
As has been suggested previously in the case series and in a limited number of prospective studies, the majority of warts, including cutaneous warts and anogenital warts, resolved following vaccine administration.
“Mostly these were common warts, plantar warts, and flat warts,” Dr. Rosen said, but the paper also reported successful treatment of recurrent respiratory papillomatosis, squamous cell carcinomas, and basal cell carcinomas.
Case reports and small studies associating HPV vaccine with successful resolution of warts are easy to find in the literature. For example, 60% of patients achieved a complete response and 30% a partial response to HPV vaccine in one small prospective study of 26 patients with genital warts. Following vaccination, no recurrences were observed after a median follow-up of more than 8 months.
In the review paper, most of the cases involved patients who received the quadrivalent HPV vaccine, Dr. Rosen noted. Only one received the updated nonavalent vaccine, which, in addition to protection against the 6, 11, 16, and 18 subtypes extends protection to subtypes 31, 33, 45, 52, and 58.
“You would expect the nonavalent vaccine to provide the same protection. It is the same vaccine. It just offers activity against more subtypes,” Dr. Rosen said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He reported that he personally has used the nonavalent vaccine successfully to treat a cutaneous wart.
The nonavalent vaccine can be administered in just two doses for those who receive the first dose before age 15. In others, it is given in three doses at 1- to 2-month intervals, according to Dr. Rosen. He said the efficacy for preventing genital warts and most HPV-related neoplasia exceeds 90%, although it is lower for penile and anal cancer. The protection extends for at least 10 years, but he said that he believes that it is likely to be longer.
“The HPV vaccine is really, really safe,” Dr. Rosen said. Besides injection-site reactions, the most common adverse event is syncope. For this reason, patients are advised to stay seated for 30 minutes after administration.
There is some evidence for cross-immunity for HPV subtypes not covered by the vaccine, particularly among children, Dr. Rosen commented. Citing the review article, he said that, although almost all HPV-associated warts resolve in children when treated with the vaccine, response is somewhat lower in adolescents and further reduced in adults.
In an interview, the senior author of the recent literature review, Natasha A. Mesinkovska, MD, PhD, associate professor of dermatology, University of California, Irvine, agreed with Dr. Rosen about the value of HPV vaccine for patients not responding to conventional therapies for HPV-related cutaneous warts.
“I think HPV vaccine is an excellent option for those patients, even older ones at 45 years of age if cost is not an issue,” she said. She did offer a caveat. In a recent statement from the International Papillomavirus Society (IPVS) on a world shortage of HPV vaccine, it was estimated that supplies might be limited for the next 3-5 years.
Given this shortage, “obtaining them currently may prove to be difficult,” she cautioned.
This publication and Global Academy for Medical Education are owned by the same parent company.
FROM COASTAL DERM
What to keep in mind as 2021 begins
As 2020 comes to a close, most of us are looking forward to a (hopefully) brighter 2021. This year has been full of challenges and new experiences, but we have learned a lot. Pandemic or not, there are some things that you and your practice can do to ensure that you are prepared to make 2021 a success.
Tips for your practice
Assess staff morale: It seems simple but checking in with your staff can go a long way. Everyone is dealing with challenges both in and out of the workplace. Check in, show them you care, and think of ways that you can make their work a positive experience in the new year. During our May 2020 GI division chief townhall, John Inadomi, MD, gave a great presentation on the importance of staff morale during the pandemic.
Listen to colleagues: Find out about their experiences, challenges, and solutions. In October, the American Gastroenterological Association held a town hall with some great information and resources called “Adapting to Changing Practice Paradigms.” The agenda covered topics from telehealth to private equity and planning for the next potential wave of COVID-19.
Celebrate the wins: It can often feel like not much went right in 2020, but we did accomplish significant wins for GIs, including achieving payment parity for telephone evaluation and management (E/M) visits with video visits, increases in digestive disease and GI cancer research funding, and inclusion/expansion of GI cancers research opportunities. We couldn’t have done it without you, though, and we will continue to need your help to move important issues forward in 2021. Get involved today! Visit “Get Involved” under Advocacy and Policy on www.gastro.org.
Prepare for E/M changes: The Current Procedural Terminology (CPT) E/M for new and established patient office/outpatient codes (99201-99205, 99211-99215), guidelines, and Medicare payments will undergo major changes beginning Jan. 1, 2021. See the AGA’s coding and reimbursement experts’ article from the March 2020 issue of GI & Hepatology News, “Prepare for major changes to E/M coding starting in 2021,” to learn about the changes and get resources to help practices prepare.
Keep up with new Medicare payment rules: The release of the 2021 physician payments and rules for the Medicare program was delayed this year because of the COVID-19 public health emergency. We were dismayed to learn that Medicare did not make any changes that substantively mitigated the expected cuts to most specialties. Instead of a 5% cut for GI, the Centers for Medicare & Medicaid Services now projects GI will experience a 4% payment cut for 2021. AGA is calling on Congress to pass legislation to stop the cuts. This situation is evolving quickly. Watch for AGA member alerts for breaking news and resources, including the AGA’s “Medicare plans significant payment cuts for 2021.”
Stay current on telehealth and telephone E/M coverage: The commercial payer community came together to cover telehealth (video visits) and telephone E/M at the beginning of the COVID-19 pandemic but have since regularly teased the end of coverage only to extend it just before it expires. It’s impossible to predict what each payer will do, but you can use the following resources to keep current on most payers’ policies and correct coding/reporting for telehealth and telephone E/M:
- “Current State Laws & Reimbursement Policies ” from the Center for Connected Health.
- “Coding for Telehealth & Virtual Visits During COVID-19” from the AGA University.
Check to see if you can report on additional quality measures: AGA has expanded the Merit-Based Incentive Payment System (MIPS) measure portfolio by assuming ownership and stewardship of two hepatitis C virus (HCV) measures from PCPI, including annually checking for HCV in active injection drug users (measure 387) and performing a one-time screening for HCV among patients at risk (measure 400). As a result, gastroenterologists can now report on even more GI-specific measures. There have been the following two changes to GI-specific measures in 2021:
- Measure 275: “Inflammatory Bowel Disease (IBD): Assessment of Hepatitis B Virus (HBV) Status Before Initiating Anti-TNF (Tumor Necrosis Factor) Therapy” now includes coding to allow reporting for all age groups, including pediatric populations.
- Measure 439: “Age Appropriate Screening Colonoscopy” now includes all colonoscopies for patients 50 years and older; however, there’s an exclusion for those patients between the ages of 50 and 85 years.
These changes will help more gastroenterologists qualify for these measures.
Dates and deadlines to remember
January 2021
- Jan. 1 – MIPS Performance Year 2021 begins.
- Jan. 4 – Submission window opens for MIPS Performance Year 2020.
- Changes to Improvement Activity category go into effect (if approved in final rule).
March 2021
- March 31 – First snapshot for Qualifying Participant (QP) determinations and MIPS APM participation.
April 2021
- April 1 – Registration begins for CMS web interface and Consumer Assessment of Healthcare Providers and Systems (CAHPS) for MIPS survey.
June 2021
- June 30 – Second snapshot for QP determinations and MIPS APM participation.
- June 30 – Registration ends for CMS web interface and CAHPS for MIPS survey.
July 2021
- CMS publishes proposed reimbursement values for 2022 in the Medicare Physician Fee Schedule proposed rule.
- CMS “Targeted Review” opens once CMS makes your MIPS payment adjustment available.
- July 1 - MIPS Performance Feedback Available. CMS will provide you with performance feedback based on the data you submitted for Performance Year 2020. You can use this feedback to improve your care and optimize the payments you receive from CMS in the future.
August 2021
- Aug. 31 - Targeted Review period closes (appeals process).
September 2021
- AMA releases CPT 2022 book, including a new CPT code for Peroral Endoscopic Myotomy (POEM).
October 2021
- Oct. 3 - Last day to start a 90-day performance period for promoting Interoperability and Improvement Activities.
November 2021
- CMS finalizes reimbursement values for 2022 in the MPFS final rule. New payment rates take effect Jan. 1, 2022.
December 2021
- Dec. 31 – Quality Payment Program Exception Applications window closes.
- Dec. 31 – MIPS Performance year 2020 ends.
- Dec. 31 – Fourth snapshot for full TIN APMs (Medicare Shared Savings Program).
G. Anton Decker, MD, is chair of the AGA Practice Management and Economics Committee, Mayo Clinic International; Dawn Francis, MD, is chair-elect of the AGA Practice Management and Economics Committee, Mayo Clinic, Jacksonville, Fla.
They have no conflicts of interest.
As 2020 comes to a close, most of us are looking forward to a (hopefully) brighter 2021. This year has been full of challenges and new experiences, but we have learned a lot. Pandemic or not, there are some things that you and your practice can do to ensure that you are prepared to make 2021 a success.
Tips for your practice
Assess staff morale: It seems simple but checking in with your staff can go a long way. Everyone is dealing with challenges both in and out of the workplace. Check in, show them you care, and think of ways that you can make their work a positive experience in the new year. During our May 2020 GI division chief townhall, John Inadomi, MD, gave a great presentation on the importance of staff morale during the pandemic.
Listen to colleagues: Find out about their experiences, challenges, and solutions. In October, the American Gastroenterological Association held a town hall with some great information and resources called “Adapting to Changing Practice Paradigms.” The agenda covered topics from telehealth to private equity and planning for the next potential wave of COVID-19.
Celebrate the wins: It can often feel like not much went right in 2020, but we did accomplish significant wins for GIs, including achieving payment parity for telephone evaluation and management (E/M) visits with video visits, increases in digestive disease and GI cancer research funding, and inclusion/expansion of GI cancers research opportunities. We couldn’t have done it without you, though, and we will continue to need your help to move important issues forward in 2021. Get involved today! Visit “Get Involved” under Advocacy and Policy on www.gastro.org.
Prepare for E/M changes: The Current Procedural Terminology (CPT) E/M for new and established patient office/outpatient codes (99201-99205, 99211-99215), guidelines, and Medicare payments will undergo major changes beginning Jan. 1, 2021. See the AGA’s coding and reimbursement experts’ article from the March 2020 issue of GI & Hepatology News, “Prepare for major changes to E/M coding starting in 2021,” to learn about the changes and get resources to help practices prepare.
Keep up with new Medicare payment rules: The release of the 2021 physician payments and rules for the Medicare program was delayed this year because of the COVID-19 public health emergency. We were dismayed to learn that Medicare did not make any changes that substantively mitigated the expected cuts to most specialties. Instead of a 5% cut for GI, the Centers for Medicare & Medicaid Services now projects GI will experience a 4% payment cut for 2021. AGA is calling on Congress to pass legislation to stop the cuts. This situation is evolving quickly. Watch for AGA member alerts for breaking news and resources, including the AGA’s “Medicare plans significant payment cuts for 2021.”
Stay current on telehealth and telephone E/M coverage: The commercial payer community came together to cover telehealth (video visits) and telephone E/M at the beginning of the COVID-19 pandemic but have since regularly teased the end of coverage only to extend it just before it expires. It’s impossible to predict what each payer will do, but you can use the following resources to keep current on most payers’ policies and correct coding/reporting for telehealth and telephone E/M:
- “Current State Laws & Reimbursement Policies ” from the Center for Connected Health.
- “Coding for Telehealth & Virtual Visits During COVID-19” from the AGA University.
Check to see if you can report on additional quality measures: AGA has expanded the Merit-Based Incentive Payment System (MIPS) measure portfolio by assuming ownership and stewardship of two hepatitis C virus (HCV) measures from PCPI, including annually checking for HCV in active injection drug users (measure 387) and performing a one-time screening for HCV among patients at risk (measure 400). As a result, gastroenterologists can now report on even more GI-specific measures. There have been the following two changes to GI-specific measures in 2021:
- Measure 275: “Inflammatory Bowel Disease (IBD): Assessment of Hepatitis B Virus (HBV) Status Before Initiating Anti-TNF (Tumor Necrosis Factor) Therapy” now includes coding to allow reporting for all age groups, including pediatric populations.
- Measure 439: “Age Appropriate Screening Colonoscopy” now includes all colonoscopies for patients 50 years and older; however, there’s an exclusion for those patients between the ages of 50 and 85 years.
These changes will help more gastroenterologists qualify for these measures.
Dates and deadlines to remember
January 2021
- Jan. 1 – MIPS Performance Year 2021 begins.
- Jan. 4 – Submission window opens for MIPS Performance Year 2020.
- Changes to Improvement Activity category go into effect (if approved in final rule).
March 2021
- March 31 – First snapshot for Qualifying Participant (QP) determinations and MIPS APM participation.
April 2021
- April 1 – Registration begins for CMS web interface and Consumer Assessment of Healthcare Providers and Systems (CAHPS) for MIPS survey.
June 2021
- June 30 – Second snapshot for QP determinations and MIPS APM participation.
- June 30 – Registration ends for CMS web interface and CAHPS for MIPS survey.
July 2021
- CMS publishes proposed reimbursement values for 2022 in the Medicare Physician Fee Schedule proposed rule.
- CMS “Targeted Review” opens once CMS makes your MIPS payment adjustment available.
- July 1 - MIPS Performance Feedback Available. CMS will provide you with performance feedback based on the data you submitted for Performance Year 2020. You can use this feedback to improve your care and optimize the payments you receive from CMS in the future.
August 2021
- Aug. 31 - Targeted Review period closes (appeals process).
September 2021
- AMA releases CPT 2022 book, including a new CPT code for Peroral Endoscopic Myotomy (POEM).
October 2021
- Oct. 3 - Last day to start a 90-day performance period for promoting Interoperability and Improvement Activities.
November 2021
- CMS finalizes reimbursement values for 2022 in the MPFS final rule. New payment rates take effect Jan. 1, 2022.
December 2021
- Dec. 31 – Quality Payment Program Exception Applications window closes.
- Dec. 31 – MIPS Performance year 2020 ends.
- Dec. 31 – Fourth snapshot for full TIN APMs (Medicare Shared Savings Program).
G. Anton Decker, MD, is chair of the AGA Practice Management and Economics Committee, Mayo Clinic International; Dawn Francis, MD, is chair-elect of the AGA Practice Management and Economics Committee, Mayo Clinic, Jacksonville, Fla.
They have no conflicts of interest.
As 2020 comes to a close, most of us are looking forward to a (hopefully) brighter 2021. This year has been full of challenges and new experiences, but we have learned a lot. Pandemic or not, there are some things that you and your practice can do to ensure that you are prepared to make 2021 a success.
Tips for your practice
Assess staff morale: It seems simple but checking in with your staff can go a long way. Everyone is dealing with challenges both in and out of the workplace. Check in, show them you care, and think of ways that you can make their work a positive experience in the new year. During our May 2020 GI division chief townhall, John Inadomi, MD, gave a great presentation on the importance of staff morale during the pandemic.
Listen to colleagues: Find out about their experiences, challenges, and solutions. In October, the American Gastroenterological Association held a town hall with some great information and resources called “Adapting to Changing Practice Paradigms.” The agenda covered topics from telehealth to private equity and planning for the next potential wave of COVID-19.
Celebrate the wins: It can often feel like not much went right in 2020, but we did accomplish significant wins for GIs, including achieving payment parity for telephone evaluation and management (E/M) visits with video visits, increases in digestive disease and GI cancer research funding, and inclusion/expansion of GI cancers research opportunities. We couldn’t have done it without you, though, and we will continue to need your help to move important issues forward in 2021. Get involved today! Visit “Get Involved” under Advocacy and Policy on www.gastro.org.
Prepare for E/M changes: The Current Procedural Terminology (CPT) E/M for new and established patient office/outpatient codes (99201-99205, 99211-99215), guidelines, and Medicare payments will undergo major changes beginning Jan. 1, 2021. See the AGA’s coding and reimbursement experts’ article from the March 2020 issue of GI & Hepatology News, “Prepare for major changes to E/M coding starting in 2021,” to learn about the changes and get resources to help practices prepare.
Keep up with new Medicare payment rules: The release of the 2021 physician payments and rules for the Medicare program was delayed this year because of the COVID-19 public health emergency. We were dismayed to learn that Medicare did not make any changes that substantively mitigated the expected cuts to most specialties. Instead of a 5% cut for GI, the Centers for Medicare & Medicaid Services now projects GI will experience a 4% payment cut for 2021. AGA is calling on Congress to pass legislation to stop the cuts. This situation is evolving quickly. Watch for AGA member alerts for breaking news and resources, including the AGA’s “Medicare plans significant payment cuts for 2021.”
Stay current on telehealth and telephone E/M coverage: The commercial payer community came together to cover telehealth (video visits) and telephone E/M at the beginning of the COVID-19 pandemic but have since regularly teased the end of coverage only to extend it just before it expires. It’s impossible to predict what each payer will do, but you can use the following resources to keep current on most payers’ policies and correct coding/reporting for telehealth and telephone E/M:
- “Current State Laws & Reimbursement Policies ” from the Center for Connected Health.
- “Coding for Telehealth & Virtual Visits During COVID-19” from the AGA University.
Check to see if you can report on additional quality measures: AGA has expanded the Merit-Based Incentive Payment System (MIPS) measure portfolio by assuming ownership and stewardship of two hepatitis C virus (HCV) measures from PCPI, including annually checking for HCV in active injection drug users (measure 387) and performing a one-time screening for HCV among patients at risk (measure 400). As a result, gastroenterologists can now report on even more GI-specific measures. There have been the following two changes to GI-specific measures in 2021:
- Measure 275: “Inflammatory Bowel Disease (IBD): Assessment of Hepatitis B Virus (HBV) Status Before Initiating Anti-TNF (Tumor Necrosis Factor) Therapy” now includes coding to allow reporting for all age groups, including pediatric populations.
- Measure 439: “Age Appropriate Screening Colonoscopy” now includes all colonoscopies for patients 50 years and older; however, there’s an exclusion for those patients between the ages of 50 and 85 years.
These changes will help more gastroenterologists qualify for these measures.
Dates and deadlines to remember
January 2021
- Jan. 1 – MIPS Performance Year 2021 begins.
- Jan. 4 – Submission window opens for MIPS Performance Year 2020.
- Changes to Improvement Activity category go into effect (if approved in final rule).
March 2021
- March 31 – First snapshot for Qualifying Participant (QP) determinations and MIPS APM participation.
April 2021
- April 1 – Registration begins for CMS web interface and Consumer Assessment of Healthcare Providers and Systems (CAHPS) for MIPS survey.
June 2021
- June 30 – Second snapshot for QP determinations and MIPS APM participation.
- June 30 – Registration ends for CMS web interface and CAHPS for MIPS survey.
July 2021
- CMS publishes proposed reimbursement values for 2022 in the Medicare Physician Fee Schedule proposed rule.
- CMS “Targeted Review” opens once CMS makes your MIPS payment adjustment available.
- July 1 - MIPS Performance Feedback Available. CMS will provide you with performance feedback based on the data you submitted for Performance Year 2020. You can use this feedback to improve your care and optimize the payments you receive from CMS in the future.
August 2021
- Aug. 31 - Targeted Review period closes (appeals process).
September 2021
- AMA releases CPT 2022 book, including a new CPT code for Peroral Endoscopic Myotomy (POEM).
October 2021
- Oct. 3 - Last day to start a 90-day performance period for promoting Interoperability and Improvement Activities.
November 2021
- CMS finalizes reimbursement values for 2022 in the MPFS final rule. New payment rates take effect Jan. 1, 2022.
December 2021
- Dec. 31 – Quality Payment Program Exception Applications window closes.
- Dec. 31 – MIPS Performance year 2020 ends.
- Dec. 31 – Fourth snapshot for full TIN APMs (Medicare Shared Savings Program).
G. Anton Decker, MD, is chair of the AGA Practice Management and Economics Committee, Mayo Clinic International; Dawn Francis, MD, is chair-elect of the AGA Practice Management and Economics Committee, Mayo Clinic, Jacksonville, Fla.
They have no conflicts of interest.
Histologic remission fails to be related to UC relapse
Relapse in ulcerative colitis patients with endoscopic remission was unaffected by histologic remission status, based on data from a retrospective study of 269 adults.
Data from previous studies suggest that histologic remission may be the strongest predictor of prognosis of disease course, wrote Neeraj Narula, MD, of McMaster University, Hamilton, Ont., and colleagues.
“However, it is unclear if UC patients who have achieved endoscopic healing have additional benefit in clinical outcomes if they have achieved histologic remission as well compared to those with ongoing histology activity,” they said.
In a study published in Alimentary Pharmacology and Therapeutics, the researchers identified 269 adults with ulcerative colitis who had endoscopic remission. Of these, 53 had normal histology, 138 had histologically inactive colitis, and 78 had histologically active colitis.
Overall, clinical relapse occurred in 64 patients, including 12 with normal histology (22.6%), 32 with inactive colitis (23.2%), and 29 with active colitis (25.6%).
No significant difference occurred in the time to relapse in patients with inactive vs. active colitis (adjusted hazard ratio 1.17, P = .67) or in patients with normal histology vs. inactive histology (AHR 0.67, P = .39). The median time to relapse was 2.92 years, 3.0 years, and 4.0 years in the normal, inactive, and active groups, respectively. Factors associated with a shorter time to relapse included older age at colonoscopy, use of 5-aminosalicylic acid, and disease extent in cases of pancolitis and left-sided colitis.
The study findings were limited by several factors including the possibility of bias in histologic scoring, lack of objective measures of disease activity, and the lack of uniformity is histologic assessment, the researchers noted. However, the results were strengthened by the large size compared with previous studies and by the adjustments for known confounding factors, they said.
“While clinical and endoscopic remission [is the target] of therapy for patients with UC, our study does not support targeting histologic remission in patients who have already achieved endoscopic remission,” they concluded.
More research may support clinical applications
“I was rather surprised by the findings, as a majority of studies have shown that histologic healing more accurately predicts clinical relapse than endoscopic remission in UC,” Atsushi Sakuraba, MD, of the University of Chicago, said in an interview.
“Although of a good sample size, this was a retrospective study, so no firm conclusion can be made,” said Dr. Sakuraba. “Using histologic healing as a therapeutic goal is still an evolving field, and it is too early to draw a conclusion as to whether (or not) to introduce histologic healing in clinical decision making,” he emphasized.
Going forward, prospective studies are needed that match for confounders such as postendoscopy medication use, age, and disease extent, Dr. Sakuraba said.
The study received no outside funding. Lead author Dr. Narula disclosed honoraria from Janssen, AbbVie, Takeda, Pfizer, Merck, and Ferring. Dr. Sakuraba had no financial conflicts to disclose.
SOURCE: Narula N et al. Aliment Pharmacol Ther. 2020 Nov 1. doi: 10.1111/apt.16147.
Relapse in ulcerative colitis patients with endoscopic remission was unaffected by histologic remission status, based on data from a retrospective study of 269 adults.
Data from previous studies suggest that histologic remission may be the strongest predictor of prognosis of disease course, wrote Neeraj Narula, MD, of McMaster University, Hamilton, Ont., and colleagues.
“However, it is unclear if UC patients who have achieved endoscopic healing have additional benefit in clinical outcomes if they have achieved histologic remission as well compared to those with ongoing histology activity,” they said.
In a study published in Alimentary Pharmacology and Therapeutics, the researchers identified 269 adults with ulcerative colitis who had endoscopic remission. Of these, 53 had normal histology, 138 had histologically inactive colitis, and 78 had histologically active colitis.
Overall, clinical relapse occurred in 64 patients, including 12 with normal histology (22.6%), 32 with inactive colitis (23.2%), and 29 with active colitis (25.6%).
No significant difference occurred in the time to relapse in patients with inactive vs. active colitis (adjusted hazard ratio 1.17, P = .67) or in patients with normal histology vs. inactive histology (AHR 0.67, P = .39). The median time to relapse was 2.92 years, 3.0 years, and 4.0 years in the normal, inactive, and active groups, respectively. Factors associated with a shorter time to relapse included older age at colonoscopy, use of 5-aminosalicylic acid, and disease extent in cases of pancolitis and left-sided colitis.
The study findings were limited by several factors including the possibility of bias in histologic scoring, lack of objective measures of disease activity, and the lack of uniformity is histologic assessment, the researchers noted. However, the results were strengthened by the large size compared with previous studies and by the adjustments for known confounding factors, they said.
“While clinical and endoscopic remission [is the target] of therapy for patients with UC, our study does not support targeting histologic remission in patients who have already achieved endoscopic remission,” they concluded.
More research may support clinical applications
“I was rather surprised by the findings, as a majority of studies have shown that histologic healing more accurately predicts clinical relapse than endoscopic remission in UC,” Atsushi Sakuraba, MD, of the University of Chicago, said in an interview.
“Although of a good sample size, this was a retrospective study, so no firm conclusion can be made,” said Dr. Sakuraba. “Using histologic healing as a therapeutic goal is still an evolving field, and it is too early to draw a conclusion as to whether (or not) to introduce histologic healing in clinical decision making,” he emphasized.
Going forward, prospective studies are needed that match for confounders such as postendoscopy medication use, age, and disease extent, Dr. Sakuraba said.
The study received no outside funding. Lead author Dr. Narula disclosed honoraria from Janssen, AbbVie, Takeda, Pfizer, Merck, and Ferring. Dr. Sakuraba had no financial conflicts to disclose.
SOURCE: Narula N et al. Aliment Pharmacol Ther. 2020 Nov 1. doi: 10.1111/apt.16147.
Relapse in ulcerative colitis patients with endoscopic remission was unaffected by histologic remission status, based on data from a retrospective study of 269 adults.
Data from previous studies suggest that histologic remission may be the strongest predictor of prognosis of disease course, wrote Neeraj Narula, MD, of McMaster University, Hamilton, Ont., and colleagues.
“However, it is unclear if UC patients who have achieved endoscopic healing have additional benefit in clinical outcomes if they have achieved histologic remission as well compared to those with ongoing histology activity,” they said.
In a study published in Alimentary Pharmacology and Therapeutics, the researchers identified 269 adults with ulcerative colitis who had endoscopic remission. Of these, 53 had normal histology, 138 had histologically inactive colitis, and 78 had histologically active colitis.
Overall, clinical relapse occurred in 64 patients, including 12 with normal histology (22.6%), 32 with inactive colitis (23.2%), and 29 with active colitis (25.6%).
No significant difference occurred in the time to relapse in patients with inactive vs. active colitis (adjusted hazard ratio 1.17, P = .67) or in patients with normal histology vs. inactive histology (AHR 0.67, P = .39). The median time to relapse was 2.92 years, 3.0 years, and 4.0 years in the normal, inactive, and active groups, respectively. Factors associated with a shorter time to relapse included older age at colonoscopy, use of 5-aminosalicylic acid, and disease extent in cases of pancolitis and left-sided colitis.
The study findings were limited by several factors including the possibility of bias in histologic scoring, lack of objective measures of disease activity, and the lack of uniformity is histologic assessment, the researchers noted. However, the results were strengthened by the large size compared with previous studies and by the adjustments for known confounding factors, they said.
“While clinical and endoscopic remission [is the target] of therapy for patients with UC, our study does not support targeting histologic remission in patients who have already achieved endoscopic remission,” they concluded.
More research may support clinical applications
“I was rather surprised by the findings, as a majority of studies have shown that histologic healing more accurately predicts clinical relapse than endoscopic remission in UC,” Atsushi Sakuraba, MD, of the University of Chicago, said in an interview.
“Although of a good sample size, this was a retrospective study, so no firm conclusion can be made,” said Dr. Sakuraba. “Using histologic healing as a therapeutic goal is still an evolving field, and it is too early to draw a conclusion as to whether (or not) to introduce histologic healing in clinical decision making,” he emphasized.
Going forward, prospective studies are needed that match for confounders such as postendoscopy medication use, age, and disease extent, Dr. Sakuraba said.
The study received no outside funding. Lead author Dr. Narula disclosed honoraria from Janssen, AbbVie, Takeda, Pfizer, Merck, and Ferring. Dr. Sakuraba had no financial conflicts to disclose.
SOURCE: Narula N et al. Aliment Pharmacol Ther. 2020 Nov 1. doi: 10.1111/apt.16147.
FROM ALIMENTARY PHARMACOLOGY AND THERAPEUTICS
Key clinical point: Histologic remission had no apparent impact on time to relapse in ulcerative colitis patients with endoscopic remission.
Major finding: The median times to relapse were 2.92 years, 3.0 years, and 4.0 years in patients with normal histology, inactive colitis, and active colitis, respectively.
Study details: The data come from a retrospective, observational study of 269 adults with ulcerative colitis with endoscopic remission.
Disclosures: The study received no outside funding. Lead author Dr. Narula disclosed honoraria from Janssen, AbbVie, Takeda, Pfizer, Merck, and Ferring. Dr. Sakuraba had no financial conflicts to disclose.
Source: Narula N et al. Aliment Pharmacol Ther. 2020 Oct 20. doi: 10.1111/apt.16147.
Vitiligo treatment options abound but consider patient goals
, according to Seemal Desai, MD, of the University of Texas, Dallas.
“We have topical steroids. We have vitamin D analogs, calcineurin inhibitors, and depigmentation therapy. We also have systemic therapy, phototherapy, surgical treatment, and even psychological therapy, Dr. Desai said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.
Head and neck vitiligo, which “tends to respond very nicely to treatment,” is one of the affected areas “where we have an important obligation to make sure our patients are effectively and aggressively treated,” he said.
According to Dr. Desai, there are three kinds of vitiligo. Active/unstable vitiligo is marked by depigmentation spreading across 1%-2% of body surface area per month, the size of about one to two palms. Refractory vitiligo responds poorly to therapy with less than 25% of affected areas experiencing repigmentation. And the third type is chronic vitiligo. “The majority of patients we see are in this phase, where depigmentation is present for at least 1 year with no history of spontaneous repigmentation.”
Before turning to therapy, he said, make sure to understand what the patient wants. “Are they even interested in being treated? I’ve had some patients with vitiligo, it’s only on their chest, and they’re always covered. They don’t even want anything. Then I have other patients who only want their face and hands treated because those are the only parts of their body that are exposed.”
To stabilize vitiligo, Dr. Desai recommends treating patients with “mini-pulse” oral therapy with systemic steroids. “I prescribe 4 milligrams of dexamethasone to be taken 2 consecutive days per week, such as Saturdays and Sundays. I usually halve the dose in children aged less than 16 years of age, so they’d be taking 2 milligrams.” Make sure, he said, to counsel patients on side effects.
He also recommends antioxidants, particularly polypodium leucotomos, “which has been shown in studies to increase the rates of head and neck repigmentation when combined with narrowband UVB.” He recommends 240 milligrams or higher, 2 or 3 times a day. He adds that alpha lipoic acid – in combination with vitamin C, vitamin E, and phototherapy – has also been shown to be effective in inducing repigmentation, especially on the head and neck.
As for newer drugs, Dr. Desai said afamelanotide, an analogue of alpha melanocyte-stimulating hormone combined with phototherapy, has shown promise. (It was approved in 2019 to increase pain free light exposure in adults with a history of phototoxic reactions related to erythropoietic protoporphyria.) Like other medications he mentioned, it isn’t FDA approved for treating vitiligo.
On another front, “Janus kinase inhibitors are our new frontier in treating vitiligo,” he said. “Tofacitinib can be dosed as an off-label usage in vitiligo in doses of 5 milligrams every other day, up to 5 milligrams daily. It’s half of the dose of rheumatoid arthritis, which is 5 milligrams b.i.d. You can actually start to see repigmentation as soon as 2 months, and then improvement up to 5 months.”
The drug requires laboratory monitoring and is expensive, he said, and JAK inhibitor side effects must be discussed with all patients.
Topical JAK inhibitors – tofacitinib 2% cream and ruxolitinib 1.5% cream – are also being evaluated as treatment for vitiligo. “I find that ruxolitinib works a little bit better, and the early bit of vitiligo data has shown that it tends to have more of a robust pigmentation response compared to tofacitinib,” said Dr. Desai, who gets these drugs compounded for topical use.
Dr. Desai added that he prefers to combine JAK inhibitors with phototherapy when possible.
For resistant vitiligo, he said, “lasers can help, especially Q-switched ruby and Q-switched Alexandrite laser. Q-switched Nd:Yag is very popular in Asia.”
In the big picture, he said, patients can benefit greatly from treatment. “Just think about the psychological improvement a patient would get by not having to get stares when walking in a mall and not having to deal with vitiligo lesions all over their cheek and neck.”
Dr. Desai disclosed performing clinical trials and/or consulting for numerous companies, including Pfizer, Allergan, AbbVie, and Dr. Reddy’s, among others. MedscapeLive and this news organization are owned by the same parent company.
, according to Seemal Desai, MD, of the University of Texas, Dallas.
“We have topical steroids. We have vitamin D analogs, calcineurin inhibitors, and depigmentation therapy. We also have systemic therapy, phototherapy, surgical treatment, and even psychological therapy, Dr. Desai said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.
Head and neck vitiligo, which “tends to respond very nicely to treatment,” is one of the affected areas “where we have an important obligation to make sure our patients are effectively and aggressively treated,” he said.
According to Dr. Desai, there are three kinds of vitiligo. Active/unstable vitiligo is marked by depigmentation spreading across 1%-2% of body surface area per month, the size of about one to two palms. Refractory vitiligo responds poorly to therapy with less than 25% of affected areas experiencing repigmentation. And the third type is chronic vitiligo. “The majority of patients we see are in this phase, where depigmentation is present for at least 1 year with no history of spontaneous repigmentation.”
Before turning to therapy, he said, make sure to understand what the patient wants. “Are they even interested in being treated? I’ve had some patients with vitiligo, it’s only on their chest, and they’re always covered. They don’t even want anything. Then I have other patients who only want their face and hands treated because those are the only parts of their body that are exposed.”
To stabilize vitiligo, Dr. Desai recommends treating patients with “mini-pulse” oral therapy with systemic steroids. “I prescribe 4 milligrams of dexamethasone to be taken 2 consecutive days per week, such as Saturdays and Sundays. I usually halve the dose in children aged less than 16 years of age, so they’d be taking 2 milligrams.” Make sure, he said, to counsel patients on side effects.
He also recommends antioxidants, particularly polypodium leucotomos, “which has been shown in studies to increase the rates of head and neck repigmentation when combined with narrowband UVB.” He recommends 240 milligrams or higher, 2 or 3 times a day. He adds that alpha lipoic acid – in combination with vitamin C, vitamin E, and phototherapy – has also been shown to be effective in inducing repigmentation, especially on the head and neck.
As for newer drugs, Dr. Desai said afamelanotide, an analogue of alpha melanocyte-stimulating hormone combined with phototherapy, has shown promise. (It was approved in 2019 to increase pain free light exposure in adults with a history of phototoxic reactions related to erythropoietic protoporphyria.) Like other medications he mentioned, it isn’t FDA approved for treating vitiligo.
On another front, “Janus kinase inhibitors are our new frontier in treating vitiligo,” he said. “Tofacitinib can be dosed as an off-label usage in vitiligo in doses of 5 milligrams every other day, up to 5 milligrams daily. It’s half of the dose of rheumatoid arthritis, which is 5 milligrams b.i.d. You can actually start to see repigmentation as soon as 2 months, and then improvement up to 5 months.”
The drug requires laboratory monitoring and is expensive, he said, and JAK inhibitor side effects must be discussed with all patients.
Topical JAK inhibitors – tofacitinib 2% cream and ruxolitinib 1.5% cream – are also being evaluated as treatment for vitiligo. “I find that ruxolitinib works a little bit better, and the early bit of vitiligo data has shown that it tends to have more of a robust pigmentation response compared to tofacitinib,” said Dr. Desai, who gets these drugs compounded for topical use.
Dr. Desai added that he prefers to combine JAK inhibitors with phototherapy when possible.
For resistant vitiligo, he said, “lasers can help, especially Q-switched ruby and Q-switched Alexandrite laser. Q-switched Nd:Yag is very popular in Asia.”
In the big picture, he said, patients can benefit greatly from treatment. “Just think about the psychological improvement a patient would get by not having to get stares when walking in a mall and not having to deal with vitiligo lesions all over their cheek and neck.”
Dr. Desai disclosed performing clinical trials and/or consulting for numerous companies, including Pfizer, Allergan, AbbVie, and Dr. Reddy’s, among others. MedscapeLive and this news organization are owned by the same parent company.
, according to Seemal Desai, MD, of the University of Texas, Dallas.
“We have topical steroids. We have vitamin D analogs, calcineurin inhibitors, and depigmentation therapy. We also have systemic therapy, phototherapy, surgical treatment, and even psychological therapy, Dr. Desai said in a presentation at MedscapeLive’s virtual Women’s & Pediatric Dermatology Seminar.
Head and neck vitiligo, which “tends to respond very nicely to treatment,” is one of the affected areas “where we have an important obligation to make sure our patients are effectively and aggressively treated,” he said.
According to Dr. Desai, there are three kinds of vitiligo. Active/unstable vitiligo is marked by depigmentation spreading across 1%-2% of body surface area per month, the size of about one to two palms. Refractory vitiligo responds poorly to therapy with less than 25% of affected areas experiencing repigmentation. And the third type is chronic vitiligo. “The majority of patients we see are in this phase, where depigmentation is present for at least 1 year with no history of spontaneous repigmentation.”
Before turning to therapy, he said, make sure to understand what the patient wants. “Are they even interested in being treated? I’ve had some patients with vitiligo, it’s only on their chest, and they’re always covered. They don’t even want anything. Then I have other patients who only want their face and hands treated because those are the only parts of their body that are exposed.”
To stabilize vitiligo, Dr. Desai recommends treating patients with “mini-pulse” oral therapy with systemic steroids. “I prescribe 4 milligrams of dexamethasone to be taken 2 consecutive days per week, such as Saturdays and Sundays. I usually halve the dose in children aged less than 16 years of age, so they’d be taking 2 milligrams.” Make sure, he said, to counsel patients on side effects.
He also recommends antioxidants, particularly polypodium leucotomos, “which has been shown in studies to increase the rates of head and neck repigmentation when combined with narrowband UVB.” He recommends 240 milligrams or higher, 2 or 3 times a day. He adds that alpha lipoic acid – in combination with vitamin C, vitamin E, and phototherapy – has also been shown to be effective in inducing repigmentation, especially on the head and neck.
As for newer drugs, Dr. Desai said afamelanotide, an analogue of alpha melanocyte-stimulating hormone combined with phototherapy, has shown promise. (It was approved in 2019 to increase pain free light exposure in adults with a history of phototoxic reactions related to erythropoietic protoporphyria.) Like other medications he mentioned, it isn’t FDA approved for treating vitiligo.
On another front, “Janus kinase inhibitors are our new frontier in treating vitiligo,” he said. “Tofacitinib can be dosed as an off-label usage in vitiligo in doses of 5 milligrams every other day, up to 5 milligrams daily. It’s half of the dose of rheumatoid arthritis, which is 5 milligrams b.i.d. You can actually start to see repigmentation as soon as 2 months, and then improvement up to 5 months.”
The drug requires laboratory monitoring and is expensive, he said, and JAK inhibitor side effects must be discussed with all patients.
Topical JAK inhibitors – tofacitinib 2% cream and ruxolitinib 1.5% cream – are also being evaluated as treatment for vitiligo. “I find that ruxolitinib works a little bit better, and the early bit of vitiligo data has shown that it tends to have more of a robust pigmentation response compared to tofacitinib,” said Dr. Desai, who gets these drugs compounded for topical use.
Dr. Desai added that he prefers to combine JAK inhibitors with phototherapy when possible.
For resistant vitiligo, he said, “lasers can help, especially Q-switched ruby and Q-switched Alexandrite laser. Q-switched Nd:Yag is very popular in Asia.”
In the big picture, he said, patients can benefit greatly from treatment. “Just think about the psychological improvement a patient would get by not having to get stares when walking in a mall and not having to deal with vitiligo lesions all over their cheek and neck.”
Dr. Desai disclosed performing clinical trials and/or consulting for numerous companies, including Pfizer, Allergan, AbbVie, and Dr. Reddy’s, among others. MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE WOMEN’S & PEDIATRIC DERMATOLOGY SEMINAR
One in five gestational carriers do not meet ASRM criteria
About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.
The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.
Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.
The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.
Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.
Protecting intended parents and carriers
“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”
ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.
“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”
Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.
“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”
A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.
To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.
Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.
Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).
When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.
Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).
An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).
Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
The role of agencies
About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.
Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”
Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.
SOURCE: Stark B et al. ASRM 2020, Abstract O-251.
About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.
The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.
Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.
The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.
Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.
Protecting intended parents and carriers
“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”
ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.
“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”
Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.
“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”
A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.
To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.
Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.
Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).
When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.
Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).
An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).
Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
The role of agencies
About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.
Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”
Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.
SOURCE: Stark B et al. ASRM 2020, Abstract O-251.
About 20% of gestational carriers at one institution did not meet recommended criteria developed by the American Society for Reproductive Medicine, according to a retrospective study of 194 patients.
The University of California, San Francisco, offers additional, stricter recommendations, including that gestational carriers have a body mass index less than 35. Under these stricter criteria, about 30% of the gestational carriers did not meet recommendations, Brett Stark, MD, MPH, reported at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.
Deviating from BMI or age recommendations may be associated with increased likelihood of spontaneous abortion, the analysis suggested. In addition, elements of a gestational carrier’s obstetric history not described in current guidelines, such as prior preterm birth, may influence gestational surrogacy outcomes.
The study was limited by incomplete information for some patients, the retrospective design, and the reliance on a relatively small cohort at a single center. Nevertheless, the findings potentially could inform discussions with patients, said Dr. Stark, a 3rd-year obstetrics and gynecology resident at the university.
Investigators aim to enroll patients in a longitudinal cohort study to further examine these questions, he said.
Protecting intended parents and carriers
“Gestational surrogacy has become an increasingly common form of third-party reproduction,” Dr. Stark said at the virtual meeting. The number of cases of in vitro fertilization (IVF) with gestational carriers increased from approximately 700 in 1999 to more than 5,500 in 2016, according to data from the Society for Assisted Reproductive Technology. “Despite the increasing prevalence of gestational carrier utilization, there remains limited guidance with regard to optimizing outcomes for both the intended parents and gestational carriers.”
ASRM and UCSF recommendations are based on expert opinion and include surprisingly little discussion about the prior pregnancy outcomes of potential gestational carriers, Dr. Stark said.
“It is important for all parties involved that we generate research and data that can help drive the development of the guidelines,” he said. Such evidence may help intended parents understand characteristics of gestational carriers that may lead to live births. “For the gestational carriers, it is important that we have information on safety so that they know they are making appropriate decisions for their family and their life.”
Gestational carrier characteristics in the present study that deviated from 2017 ASRM recommendations included age less than 21 years or greater than 45 years, mental health conditions, and having more than five prior deliveries.
“ASRM guidelines focused on criteria for gestational carriers are meant to protect infertile couples, the carrier, as well as the supporting agency,” Alan Penzias, MD, chair of ASRM’s Practice Committee who is in private practice in Boston, said in a society news release that highlighted Dr. Stark’s study. “It is important that gestational carriers have a complete medical history and examination, in addition to a psychological session with a mental health professional to ensure there are no reasons for the carrier to not move forward with pregnancy.”
A retrospective study by Kate Swanson, MD, and associates found that nonadherence to ASRM guidelines was associated with increased rates of cesarean delivery, neonatal morbidity, and preterm birth.
To examine how adherence to ASRM and UCSF recommendations relates to pregnancy outcomes and maternal and neonatal morbidity and death, Dr. Stark and colleagues assessed births from gestational carrier pregnancies at UCSF between 2008 and 2019.
Of 194 gestational carriers included in the analysis, 98.9% had a prior term pregnancy, 11.9% had a prior preterm pregnancy, and 17.5% had a prior spontaneous abortion.
Indications for use of gestational surrogates included serious medical condition of intended parent (25%), uterine factor infertility (23%), recurrent pregnancy loss (10%), and same-sex male couples (8%).
When the researchers compared pregnancy outcomes for gestational carriers who met ASRM guidelines with outcomes for 38 gestational carriers who did not meet ASRM guidelines, there were no statistically significant differences. Antepartum, intrapartum, and postpartum complication rates and cesarean delivery rates did not significantly differ based on ASRM guideline adherence.
Nonadherence to the stricter UCSF guidelines, however, was associated with increased likelihood of spontaneous abortion. In all, 23.7% of the 59 gestational carriers who were nonadherent to UCSF guidelines had a pregnancy end in a spontaneous abortion, compared with 6.7% of gestational carriers who were adherent to the UCSF recommendations (odds ratio, 4.35).
An analysis of individual criteria and poor pregnancy outcomes found that BMI greater than 35 was associated with increased likelihood of spontaneous abortion (OR, 4.29), as was age less than 21 years or greater than 45 years (OR, 3.37).
Prior spontaneous abortion was associated with increased likelihood of a biochemical pregnancy (OR, 3.2), and prior preterm birth was associated with increased likelihood of spontaneous abortion (OR, 3.19), previable delivery (OR, 25.2), cesarean delivery (OR, 2.59), and antepartum complications (OR, 3.56).
The role of agencies
About 76% of the gestational carriers had pregnancies mediated through a gestational surrogacy agency. Surrogates from agencies were about three times more likely than surrogates who were family, friends, or from private surrogacy arrangements to adhere to ASRM and UCSF guidelines.
Even after hearing about gestational carrier recommendations, patients may prefer to work with someone they know. “We want to provide our patients with evidence-based information if possible, but ultimately it is their decision to make,” Dr. Stark said. “And we just need to make sure that they are making an informed decision.”
Dr. Stark had no relevant disclosures. Dr. Penzias helped develop the ASRM committee opinion. He had no relevant conflicts of interest.
SOURCE: Stark B et al. ASRM 2020, Abstract O-251.
FROM ASRM 2020
Top AGA Community patient cases
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
Which of the following patients needs a liver biopsy and why? (https://community.gastro.org/posts/23108)
Next steps for a Crohn’s patient (https://community.gastro.org/posts/23000)
Fecal calprotectin versus histology (https://community.gastro.org/posts/22969)
Collecting and sending specimen for disaccharidase assay (https://community.gastro.org/posts/23092)
Roundtables (https://community.gastro.org/discussions)
Q&A with CRC task force: Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
Which of the following patients needs a liver biopsy and why? (https://community.gastro.org/posts/23108)
Next steps for a Crohn’s patient (https://community.gastro.org/posts/23000)
Fecal calprotectin versus histology (https://community.gastro.org/posts/22969)
Collecting and sending specimen for disaccharidase assay (https://community.gastro.org/posts/23092)
Roundtables (https://community.gastro.org/discussions)
Q&A with CRC task force: Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
Which of the following patients needs a liver biopsy and why? (https://community.gastro.org/posts/23108)
Next steps for a Crohn’s patient (https://community.gastro.org/posts/23000)
Fecal calprotectin versus histology (https://community.gastro.org/posts/22969)
Collecting and sending specimen for disaccharidase assay (https://community.gastro.org/posts/23092)
Roundtables (https://community.gastro.org/discussions)
Q&A with CRC task force: Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
Expert picks top pediatric dermatology studies of 2020
Lawrence F. Eichenfield, MD, said at the annual Coastal Dermatology Symposium, held virtually.
Dr. Eichenfield, professor of dermatology and pediatrics, at the University of California, San Diego, presented a list of studies, some of which resulted in approvals of pediatric indications in 2020, that he believes deserve attention.
Crisaborole
Crisaborole ointment, 2% is now approved for topical treatment of children aged as young as 3 months, based on the results of the CrisADe CARE1 phase 4 study. In this open-label study of infants aged from 3 months to under 2 years with mild to moderate AD, treated with crisaborole twice a day for 28 days, the mean reduction from baseline in the Eczema Area and Severity Index (EASI) score was 49.6% on day 15 and 57.5% on day 29. The most common side effects were erythema and application-site pain, but neither occurred in more than 4% of patients. The discontinuation rate was less than 3%.
When the indication for treatment of young children down to age 3 months (from 24 months) was granted by the Food and Drug Administration in March 2020, crisaborole, a phosphodiesterase-4 inhibitor, became the only nonsteroidal approved for treatment of AD in children aged younger than 2 years, Dr. Eichenfield pointed out.
Tacrolimus
The topical calcineurin inhibitor tacrolimus (Protopic) poses no detectable risk of cancer in children treated for AD, according to a prospective, multinational study that followed nearly 8,000 children with AD who used topical tacrolimus for at least 6 weeks over 10 years. With 44,469 person-years of follow-up in a population with at least 6 weeks of exposure to tacrolimus, there were six confirmed cancers, a rate not different than background rates, and no lymphomas.
“I have always tried to educate my patients about the potential use of the topical calcineurin inhibitors while reassuring them that the data did not support significant risk,” Dr. Eichenfield said. However, a large set of data reconfirming a low risk of cancer, although not definitive, “are really nice to have.”
Ruxolitinib
For treatment of AD in children aged as young as 12 years, a cream formulation of ruxolitinib, a Janus kinase 1/JAK2 inhibitor, met its primary outcomes in the phase 3 TRuE AD1 and TRuE AD2 trials. (These data are not yet published but were presented at the Revolutionizing Atopic Dermatitis virtual symposium in April 2020.) The primary endpoint of 75% EASI clearance (EASI-75) was achieved in approximately 62% of patients treated with the 1.5% dose of ruxolitinib twice daily. This was a highly significant advantage over vehicle in both studies (P < .0001).
The EASI-75 rates at 8 weeks for the 0.75% formulation, at 56% and 51.5% for the TRuE AD1 and TRuE AD2 trials, respectively, were lower but also superior (P < .0001) to the 24.6% and 14.4% response rates on vehicle, respectively.
Emphasizing a consistent benefit on multiple secondary endpoints, including the “really early itch decrease,” Dr. Eichenfield described the phase 3 data as “really excellent results.” The data have not yet led to FDA approval of ruxolitinib for AD, but approval seems likely. Dr. Eichenfield noted that other drugs in the same class, such as abrocitinib and upadacitinib, have also demonstrated promising efficacy in children aged 12 years or older.
Dupilumab
Dupilumab, an interleukin-4 receptor alpha antagonist, was approved in May, 2020, for the treatment of AD in children ages 6-11 years, on the basis of a recently published phase 3, randomized, placebo-controlled trial that enrolled children aged between 6 and 11 years, comparing dupilumab and topical corticosteroids and placebo plus topical corticosteroids. Severe involvement was an entry criterion.
At 16 weeks, an EASI-75 response was achieved by 67% of the group randomized to 200 mg of dupilumab administered every 2 weeks and 70% of the group randomized to 300 mg every 4 weeks versus 27% of those randomized to placebo. More patients in the dupilumab arms developed conjunctivitis (10.8% vs. 4.7%) and had injection-site reactions (8.5% vs. 3.5%), but the monoclonal antibody was otherwise well tolerated and safe.
These data suggest that younger patients with severe disease “do, if anything, better than adults,” Dr. Eichenfield said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He cautioned that avoiding live vaccines, which is recommended in patients on dupilumab, “is likely more of an issue in children.”
Ixekizumab
Ixekizumab has been approved for pediatric patients aged as young as 6 years who are eligible for systemic therapy on the basis of a phase 3 trial. For the primary endpoint of 75% clearance on the Psoriasis Area and Severity Index, the response rates were 89% for the IL-17 inhibitor administered every 4 weeks and 25% for placebo. The study also associated ixekizumab with a significant improvement in quality of life.
The availability of more targeted therapies for children are likely. In Europe, secukinumab, another IL-17 inhibitor, was approved for treatment in pediatric patients this past summer, Dr. Eichenfield noted. These data are not yet published, but he expects targeted therapies to join a growing list of biologics already approved in children.
For drugs with established efficacy and safety, he advised, “look at your pediatric psoriasis patients and don’t be wimpy.” In children with poorly controlled psoriasis, he concluded these drugs have been associated with improved quality of life.
In November 2019, the American Academy of Dermatology and National Psoriasis Foundation published psoriasis management guidelines for children. Not all of the most recently approved therapies are included in these guidelines, which are the first to provide specific recommendations for children, but Dr. Eichenfield also included this publication among his top picks for important contributions to the pediatric dermatology literature in 2020.
Dr. Eichenfield reported financial relationships with 20 pharmaceutical companies that manufacture dermatologic products, including those for the diseases he discussed.
This publication and Global Academy for Medical Education are owned by the same parent company.
Lawrence F. Eichenfield, MD, said at the annual Coastal Dermatology Symposium, held virtually.
Dr. Eichenfield, professor of dermatology and pediatrics, at the University of California, San Diego, presented a list of studies, some of which resulted in approvals of pediatric indications in 2020, that he believes deserve attention.
Crisaborole
Crisaborole ointment, 2% is now approved for topical treatment of children aged as young as 3 months, based on the results of the CrisADe CARE1 phase 4 study. In this open-label study of infants aged from 3 months to under 2 years with mild to moderate AD, treated with crisaborole twice a day for 28 days, the mean reduction from baseline in the Eczema Area and Severity Index (EASI) score was 49.6% on day 15 and 57.5% on day 29. The most common side effects were erythema and application-site pain, but neither occurred in more than 4% of patients. The discontinuation rate was less than 3%.
When the indication for treatment of young children down to age 3 months (from 24 months) was granted by the Food and Drug Administration in March 2020, crisaborole, a phosphodiesterase-4 inhibitor, became the only nonsteroidal approved for treatment of AD in children aged younger than 2 years, Dr. Eichenfield pointed out.
Tacrolimus
The topical calcineurin inhibitor tacrolimus (Protopic) poses no detectable risk of cancer in children treated for AD, according to a prospective, multinational study that followed nearly 8,000 children with AD who used topical tacrolimus for at least 6 weeks over 10 years. With 44,469 person-years of follow-up in a population with at least 6 weeks of exposure to tacrolimus, there were six confirmed cancers, a rate not different than background rates, and no lymphomas.
“I have always tried to educate my patients about the potential use of the topical calcineurin inhibitors while reassuring them that the data did not support significant risk,” Dr. Eichenfield said. However, a large set of data reconfirming a low risk of cancer, although not definitive, “are really nice to have.”
Ruxolitinib
For treatment of AD in children aged as young as 12 years, a cream formulation of ruxolitinib, a Janus kinase 1/JAK2 inhibitor, met its primary outcomes in the phase 3 TRuE AD1 and TRuE AD2 trials. (These data are not yet published but were presented at the Revolutionizing Atopic Dermatitis virtual symposium in April 2020.) The primary endpoint of 75% EASI clearance (EASI-75) was achieved in approximately 62% of patients treated with the 1.5% dose of ruxolitinib twice daily. This was a highly significant advantage over vehicle in both studies (P < .0001).
The EASI-75 rates at 8 weeks for the 0.75% formulation, at 56% and 51.5% for the TRuE AD1 and TRuE AD2 trials, respectively, were lower but also superior (P < .0001) to the 24.6% and 14.4% response rates on vehicle, respectively.
Emphasizing a consistent benefit on multiple secondary endpoints, including the “really early itch decrease,” Dr. Eichenfield described the phase 3 data as “really excellent results.” The data have not yet led to FDA approval of ruxolitinib for AD, but approval seems likely. Dr. Eichenfield noted that other drugs in the same class, such as abrocitinib and upadacitinib, have also demonstrated promising efficacy in children aged 12 years or older.
Dupilumab
Dupilumab, an interleukin-4 receptor alpha antagonist, was approved in May, 2020, for the treatment of AD in children ages 6-11 years, on the basis of a recently published phase 3, randomized, placebo-controlled trial that enrolled children aged between 6 and 11 years, comparing dupilumab and topical corticosteroids and placebo plus topical corticosteroids. Severe involvement was an entry criterion.
At 16 weeks, an EASI-75 response was achieved by 67% of the group randomized to 200 mg of dupilumab administered every 2 weeks and 70% of the group randomized to 300 mg every 4 weeks versus 27% of those randomized to placebo. More patients in the dupilumab arms developed conjunctivitis (10.8% vs. 4.7%) and had injection-site reactions (8.5% vs. 3.5%), but the monoclonal antibody was otherwise well tolerated and safe.
These data suggest that younger patients with severe disease “do, if anything, better than adults,” Dr. Eichenfield said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He cautioned that avoiding live vaccines, which is recommended in patients on dupilumab, “is likely more of an issue in children.”
Ixekizumab
Ixekizumab has been approved for pediatric patients aged as young as 6 years who are eligible for systemic therapy on the basis of a phase 3 trial. For the primary endpoint of 75% clearance on the Psoriasis Area and Severity Index, the response rates were 89% for the IL-17 inhibitor administered every 4 weeks and 25% for placebo. The study also associated ixekizumab with a significant improvement in quality of life.
The availability of more targeted therapies for children are likely. In Europe, secukinumab, another IL-17 inhibitor, was approved for treatment in pediatric patients this past summer, Dr. Eichenfield noted. These data are not yet published, but he expects targeted therapies to join a growing list of biologics already approved in children.
For drugs with established efficacy and safety, he advised, “look at your pediatric psoriasis patients and don’t be wimpy.” In children with poorly controlled psoriasis, he concluded these drugs have been associated with improved quality of life.
In November 2019, the American Academy of Dermatology and National Psoriasis Foundation published psoriasis management guidelines for children. Not all of the most recently approved therapies are included in these guidelines, which are the first to provide specific recommendations for children, but Dr. Eichenfield also included this publication among his top picks for important contributions to the pediatric dermatology literature in 2020.
Dr. Eichenfield reported financial relationships with 20 pharmaceutical companies that manufacture dermatologic products, including those for the diseases he discussed.
This publication and Global Academy for Medical Education are owned by the same parent company.
Lawrence F. Eichenfield, MD, said at the annual Coastal Dermatology Symposium, held virtually.
Dr. Eichenfield, professor of dermatology and pediatrics, at the University of California, San Diego, presented a list of studies, some of which resulted in approvals of pediatric indications in 2020, that he believes deserve attention.
Crisaborole
Crisaborole ointment, 2% is now approved for topical treatment of children aged as young as 3 months, based on the results of the CrisADe CARE1 phase 4 study. In this open-label study of infants aged from 3 months to under 2 years with mild to moderate AD, treated with crisaborole twice a day for 28 days, the mean reduction from baseline in the Eczema Area and Severity Index (EASI) score was 49.6% on day 15 and 57.5% on day 29. The most common side effects were erythema and application-site pain, but neither occurred in more than 4% of patients. The discontinuation rate was less than 3%.
When the indication for treatment of young children down to age 3 months (from 24 months) was granted by the Food and Drug Administration in March 2020, crisaborole, a phosphodiesterase-4 inhibitor, became the only nonsteroidal approved for treatment of AD in children aged younger than 2 years, Dr. Eichenfield pointed out.
Tacrolimus
The topical calcineurin inhibitor tacrolimus (Protopic) poses no detectable risk of cancer in children treated for AD, according to a prospective, multinational study that followed nearly 8,000 children with AD who used topical tacrolimus for at least 6 weeks over 10 years. With 44,469 person-years of follow-up in a population with at least 6 weeks of exposure to tacrolimus, there were six confirmed cancers, a rate not different than background rates, and no lymphomas.
“I have always tried to educate my patients about the potential use of the topical calcineurin inhibitors while reassuring them that the data did not support significant risk,” Dr. Eichenfield said. However, a large set of data reconfirming a low risk of cancer, although not definitive, “are really nice to have.”
Ruxolitinib
For treatment of AD in children aged as young as 12 years, a cream formulation of ruxolitinib, a Janus kinase 1/JAK2 inhibitor, met its primary outcomes in the phase 3 TRuE AD1 and TRuE AD2 trials. (These data are not yet published but were presented at the Revolutionizing Atopic Dermatitis virtual symposium in April 2020.) The primary endpoint of 75% EASI clearance (EASI-75) was achieved in approximately 62% of patients treated with the 1.5% dose of ruxolitinib twice daily. This was a highly significant advantage over vehicle in both studies (P < .0001).
The EASI-75 rates at 8 weeks for the 0.75% formulation, at 56% and 51.5% for the TRuE AD1 and TRuE AD2 trials, respectively, were lower but also superior (P < .0001) to the 24.6% and 14.4% response rates on vehicle, respectively.
Emphasizing a consistent benefit on multiple secondary endpoints, including the “really early itch decrease,” Dr. Eichenfield described the phase 3 data as “really excellent results.” The data have not yet led to FDA approval of ruxolitinib for AD, but approval seems likely. Dr. Eichenfield noted that other drugs in the same class, such as abrocitinib and upadacitinib, have also demonstrated promising efficacy in children aged 12 years or older.
Dupilumab
Dupilumab, an interleukin-4 receptor alpha antagonist, was approved in May, 2020, for the treatment of AD in children ages 6-11 years, on the basis of a recently published phase 3, randomized, placebo-controlled trial that enrolled children aged between 6 and 11 years, comparing dupilumab and topical corticosteroids and placebo plus topical corticosteroids. Severe involvement was an entry criterion.
At 16 weeks, an EASI-75 response was achieved by 67% of the group randomized to 200 mg of dupilumab administered every 2 weeks and 70% of the group randomized to 300 mg every 4 weeks versus 27% of those randomized to placebo. More patients in the dupilumab arms developed conjunctivitis (10.8% vs. 4.7%) and had injection-site reactions (8.5% vs. 3.5%), but the monoclonal antibody was otherwise well tolerated and safe.
These data suggest that younger patients with severe disease “do, if anything, better than adults,” Dr. Eichenfield said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He cautioned that avoiding live vaccines, which is recommended in patients on dupilumab, “is likely more of an issue in children.”
Ixekizumab
Ixekizumab has been approved for pediatric patients aged as young as 6 years who are eligible for systemic therapy on the basis of a phase 3 trial. For the primary endpoint of 75% clearance on the Psoriasis Area and Severity Index, the response rates were 89% for the IL-17 inhibitor administered every 4 weeks and 25% for placebo. The study also associated ixekizumab with a significant improvement in quality of life.
The availability of more targeted therapies for children are likely. In Europe, secukinumab, another IL-17 inhibitor, was approved for treatment in pediatric patients this past summer, Dr. Eichenfield noted. These data are not yet published, but he expects targeted therapies to join a growing list of biologics already approved in children.
For drugs with established efficacy and safety, he advised, “look at your pediatric psoriasis patients and don’t be wimpy.” In children with poorly controlled psoriasis, he concluded these drugs have been associated with improved quality of life.
In November 2019, the American Academy of Dermatology and National Psoriasis Foundation published psoriasis management guidelines for children. Not all of the most recently approved therapies are included in these guidelines, which are the first to provide specific recommendations for children, but Dr. Eichenfield also included this publication among his top picks for important contributions to the pediatric dermatology literature in 2020.
Dr. Eichenfield reported financial relationships with 20 pharmaceutical companies that manufacture dermatologic products, including those for the diseases he discussed.
This publication and Global Academy for Medical Education are owned by the same parent company.
FROM COASTAL DERM
Getting closer to a lifesaving RSV vaccine
Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.
RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”
“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”
As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”
The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.
“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”
These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.
One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.
Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”
Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.
Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.
Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.
“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.
Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”
Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.
Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.
RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”
“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”
As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”
The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.
“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”
These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.
One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.
Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”
Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.
Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.
Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.
“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.
Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”
Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.
Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.
RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”
“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”
As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”
The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.
“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”
These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.
One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.
Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”
Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.
Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.
Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.
“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.
Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”
Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.
FROM ESPID 2020