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Sorting out sleep complaints in children with AD can be complex
according to Stephen H. Sheldon, DO.
“They wake up frequently,” Dr. Sheldon, professor of pediatrics and neurology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis symposium. “They may not stay up for long periods of time, but they move about often. There’s a loss of about 50 minutes of sleep per night in children with AD. This loss can result in significant sleep debt the following day. They have difficulty settling at night. Once they get into bed, they have difficulty falling asleep, and many of them have difficulty staying asleep.”
At the sleep medicine center at Lurie Children’s Hospital of Chicago, he and his colleagues have observed that some children with AD complain of difficulty with limb movements. “Part of the issue has been that they have been diagnosed with different sleep-related disorders, such as period limb movement disorder, restless leg syndrome, and growing pain,” Dr. Sheldon said. “Often, they do not know how to describe the manifestations of their leg discomfort in restless leg syndrome and period limb movement disorder and limb movements of sleep.”
Children who complain of growing pains say that their legs hurt, he continued. Sometimes they’ll say that they feel like spiders are crawling on their legs, or that their legs itch, but they often say they have pain in their legs that wakes them up and keeps them from keeping their legs still.
According to the American Academy of Sleep Medicine, periodic limb movement disorder of sleep is characterized by frequent limb movements that last at least 0.5 seconds and are separated by no more than 90 seconds. “They’re four movements in a row that are at least 5 seconds apart,” Dr. Sheldon said.
Interestingly, he added, children who have limb movement disorder have symptoms during the day, similar to adults. “But we see many children with periodic limb movements of sleep whose arms and legs are moving all night, and they don’t have many symptoms during the day.” These children may have difficulty falling or staying asleep, but do not fulfill all of the American Academy of Sleep Medicine criteria for diagnosis of periodic limb movement disorder, he added.
In 2018, Lourdes M. DelRosso, MD, EdD, of Seattle Children’s Hospital, and colleagues described a new sleep problem they termed restless sleep disorder: those who do not fit the criteria for any other sleep disorder but have daytime impairment.
“On video they have very frequent movements – more than five movements an hour of major body activity,” Dr. Sheldon explained. “They’ll move their trunk, their legs, and reposition themselves. We have found that there are many children who presented to the sleep disorder center with restless sleep, limb movement disorder, periodic limb movements of sleep, and daytime symptoms that would fulfill the criteria of periodic limb movement disorder but also have atopic dermatitis.”
Recently, Dr. Sheldon and his colleagues used polysomnographic variables to study children who presented to Lurie Children’s Hospital with AD and symptoms such as difficulty maintaining sleep and snoring with allergic rhinitis. They found that there were increased periods of being awake after the onset of sleep, “meaning the children fell asleep fairly easily in the beginning of the night but they had significant wake after they fell asleep,” he said. “They would wake up in the middle of the night and stay awake for long periods of time – either one long session or multiple shorter sessions throughout the night. They had increased total limb movements per hour of sleep. This means that their limb movements were greater than five events per hour of sleep and it resulted in restless sleep and limb movements that would fulfill the criteria of periodic limb movement disorder.”
Most of these children had mild to moderate AD, he continued. “We feel that the sensory afferent loop in these youngsters doesn’t really turn off completely when they’re asleep. This is ripe for further study, but it makes intuitive sense that if the sensory afferent loop continues during sleep, it may affect the arousal system significantly.”
Dr. Sheldon recommended that any child who presents with a diagnosis of periodic limb movement disorder, periodic limb movements of sleep, or restless sleep disorder should be evaluated for AD. “The treatment then, would first require differentiation between periodic limb movement disorder of sleep and AD. Both should be addressed at the same time in order to solve the child’s daytime AD problem as well as the sleep-related issues that occur with an AD diagnosis.”
He reported having no financial disclosures.
according to Stephen H. Sheldon, DO.
“They wake up frequently,” Dr. Sheldon, professor of pediatrics and neurology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis symposium. “They may not stay up for long periods of time, but they move about often. There’s a loss of about 50 minutes of sleep per night in children with AD. This loss can result in significant sleep debt the following day. They have difficulty settling at night. Once they get into bed, they have difficulty falling asleep, and many of them have difficulty staying asleep.”
At the sleep medicine center at Lurie Children’s Hospital of Chicago, he and his colleagues have observed that some children with AD complain of difficulty with limb movements. “Part of the issue has been that they have been diagnosed with different sleep-related disorders, such as period limb movement disorder, restless leg syndrome, and growing pain,” Dr. Sheldon said. “Often, they do not know how to describe the manifestations of their leg discomfort in restless leg syndrome and period limb movement disorder and limb movements of sleep.”
Children who complain of growing pains say that their legs hurt, he continued. Sometimes they’ll say that they feel like spiders are crawling on their legs, or that their legs itch, but they often say they have pain in their legs that wakes them up and keeps them from keeping their legs still.
According to the American Academy of Sleep Medicine, periodic limb movement disorder of sleep is characterized by frequent limb movements that last at least 0.5 seconds and are separated by no more than 90 seconds. “They’re four movements in a row that are at least 5 seconds apart,” Dr. Sheldon said.
Interestingly, he added, children who have limb movement disorder have symptoms during the day, similar to adults. “But we see many children with periodic limb movements of sleep whose arms and legs are moving all night, and they don’t have many symptoms during the day.” These children may have difficulty falling or staying asleep, but do not fulfill all of the American Academy of Sleep Medicine criteria for diagnosis of periodic limb movement disorder, he added.
In 2018, Lourdes M. DelRosso, MD, EdD, of Seattle Children’s Hospital, and colleagues described a new sleep problem they termed restless sleep disorder: those who do not fit the criteria for any other sleep disorder but have daytime impairment.
“On video they have very frequent movements – more than five movements an hour of major body activity,” Dr. Sheldon explained. “They’ll move their trunk, their legs, and reposition themselves. We have found that there are many children who presented to the sleep disorder center with restless sleep, limb movement disorder, periodic limb movements of sleep, and daytime symptoms that would fulfill the criteria of periodic limb movement disorder but also have atopic dermatitis.”
Recently, Dr. Sheldon and his colleagues used polysomnographic variables to study children who presented to Lurie Children’s Hospital with AD and symptoms such as difficulty maintaining sleep and snoring with allergic rhinitis. They found that there were increased periods of being awake after the onset of sleep, “meaning the children fell asleep fairly easily in the beginning of the night but they had significant wake after they fell asleep,” he said. “They would wake up in the middle of the night and stay awake for long periods of time – either one long session or multiple shorter sessions throughout the night. They had increased total limb movements per hour of sleep. This means that their limb movements were greater than five events per hour of sleep and it resulted in restless sleep and limb movements that would fulfill the criteria of periodic limb movement disorder.”
Most of these children had mild to moderate AD, he continued. “We feel that the sensory afferent loop in these youngsters doesn’t really turn off completely when they’re asleep. This is ripe for further study, but it makes intuitive sense that if the sensory afferent loop continues during sleep, it may affect the arousal system significantly.”
Dr. Sheldon recommended that any child who presents with a diagnosis of periodic limb movement disorder, periodic limb movements of sleep, or restless sleep disorder should be evaluated for AD. “The treatment then, would first require differentiation between periodic limb movement disorder of sleep and AD. Both should be addressed at the same time in order to solve the child’s daytime AD problem as well as the sleep-related issues that occur with an AD diagnosis.”
He reported having no financial disclosures.
according to Stephen H. Sheldon, DO.
“They wake up frequently,” Dr. Sheldon, professor of pediatrics and neurology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis symposium. “They may not stay up for long periods of time, but they move about often. There’s a loss of about 50 minutes of sleep per night in children with AD. This loss can result in significant sleep debt the following day. They have difficulty settling at night. Once they get into bed, they have difficulty falling asleep, and many of them have difficulty staying asleep.”
At the sleep medicine center at Lurie Children’s Hospital of Chicago, he and his colleagues have observed that some children with AD complain of difficulty with limb movements. “Part of the issue has been that they have been diagnosed with different sleep-related disorders, such as period limb movement disorder, restless leg syndrome, and growing pain,” Dr. Sheldon said. “Often, they do not know how to describe the manifestations of their leg discomfort in restless leg syndrome and period limb movement disorder and limb movements of sleep.”
Children who complain of growing pains say that their legs hurt, he continued. Sometimes they’ll say that they feel like spiders are crawling on their legs, or that their legs itch, but they often say they have pain in their legs that wakes them up and keeps them from keeping their legs still.
According to the American Academy of Sleep Medicine, periodic limb movement disorder of sleep is characterized by frequent limb movements that last at least 0.5 seconds and are separated by no more than 90 seconds. “They’re four movements in a row that are at least 5 seconds apart,” Dr. Sheldon said.
Interestingly, he added, children who have limb movement disorder have symptoms during the day, similar to adults. “But we see many children with periodic limb movements of sleep whose arms and legs are moving all night, and they don’t have many symptoms during the day.” These children may have difficulty falling or staying asleep, but do not fulfill all of the American Academy of Sleep Medicine criteria for diagnosis of periodic limb movement disorder, he added.
In 2018, Lourdes M. DelRosso, MD, EdD, of Seattle Children’s Hospital, and colleagues described a new sleep problem they termed restless sleep disorder: those who do not fit the criteria for any other sleep disorder but have daytime impairment.
“On video they have very frequent movements – more than five movements an hour of major body activity,” Dr. Sheldon explained. “They’ll move their trunk, their legs, and reposition themselves. We have found that there are many children who presented to the sleep disorder center with restless sleep, limb movement disorder, periodic limb movements of sleep, and daytime symptoms that would fulfill the criteria of periodic limb movement disorder but also have atopic dermatitis.”
Recently, Dr. Sheldon and his colleagues used polysomnographic variables to study children who presented to Lurie Children’s Hospital with AD and symptoms such as difficulty maintaining sleep and snoring with allergic rhinitis. They found that there were increased periods of being awake after the onset of sleep, “meaning the children fell asleep fairly easily in the beginning of the night but they had significant wake after they fell asleep,” he said. “They would wake up in the middle of the night and stay awake for long periods of time – either one long session or multiple shorter sessions throughout the night. They had increased total limb movements per hour of sleep. This means that their limb movements were greater than five events per hour of sleep and it resulted in restless sleep and limb movements that would fulfill the criteria of periodic limb movement disorder.”
Most of these children had mild to moderate AD, he continued. “We feel that the sensory afferent loop in these youngsters doesn’t really turn off completely when they’re asleep. This is ripe for further study, but it makes intuitive sense that if the sensory afferent loop continues during sleep, it may affect the arousal system significantly.”
Dr. Sheldon recommended that any child who presents with a diagnosis of periodic limb movement disorder, periodic limb movements of sleep, or restless sleep disorder should be evaluated for AD. “The treatment then, would first require differentiation between periodic limb movement disorder of sleep and AD. Both should be addressed at the same time in order to solve the child’s daytime AD problem as well as the sleep-related issues that occur with an AD diagnosis.”
He reported having no financial disclosures.
FROM RAD 2021
Key questions to ask atopic dermatitis patients with sleep complaints
If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.
According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.
During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:
When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.
How long does it take for you to fall asleep?
Do you wake up in the middle of the night, and for how long? What do you do if you wake up?
When do you wake up in the morning? Is it on your own, or with an alarm clock?
Does this schedule change on nonworkdays?
Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?
Do you snore? Meaning, is there concern for sleep apnea?
Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.
The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”
Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.
Dr. Abbott reported having no financial disclosures.
If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.
According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.
During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:
When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.
How long does it take for you to fall asleep?
Do you wake up in the middle of the night, and for how long? What do you do if you wake up?
When do you wake up in the morning? Is it on your own, or with an alarm clock?
Does this schedule change on nonworkdays?
Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?
Do you snore? Meaning, is there concern for sleep apnea?
Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.
The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”
Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.
Dr. Abbott reported having no financial disclosures.
If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.
According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.
During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:
When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.
How long does it take for you to fall asleep?
Do you wake up in the middle of the night, and for how long? What do you do if you wake up?
When do you wake up in the morning? Is it on your own, or with an alarm clock?
Does this schedule change on nonworkdays?
Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?
Do you snore? Meaning, is there concern for sleep apnea?
Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.
The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”
Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.
Dr. Abbott reported having no financial disclosures.
FROM REVOLUTIONIZING AD 2021
Longitudinal course of atopic dermatitis often overlooked, expert says
In the opinion of Raj Chovatiya, MD, PhD, the longitudinal course of atopic dermatitis (AD) is an important yet overlooked clinical domain of the disease.
“We know that AD is associated with fluctuating severity, disease flares, long-term persistence, and periods of quiescence, but its longitudinal course is not routinely incorporated into guidelines or clinical trials,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis virtual symposium. “Understanding the long-term course may improve our ability to phenotype, prognosticate, and personalize our care.”
The classic view of AD is that it starts in early childhood, follows a waxing and waning course for a few years, and burns out by adulthood. “I think we all know that this is generally false,” he said. “This was largely based on anecdotal clinical experience and large cross-sectional studies, not ones that consider the heterogeneity of AD.”
Results from a large-scale, prospective study of 7,157 children enrolled in the Pediatric Eczema Elective Registry (PEER), suggests that AD commonly persists beyond adulthood. PEER was a phase IV postmarketing safety study of children aged 12-17 with moderate to severe AD who were exposed to topical pimecrolimus and who were surveyed every 6 months (JAMA Dermatol. 2014;150[6]:593-600). The researchers found that more persistent disease was associated with self-reported disease activity, many environmental exposures, White race, history of AD, and an annual household income of less than $50,000. By age 20, 50% reported at least one 6-month symptom- and medication-free period. “The important takeaway was that at every age, greater than 80% reported active AD as defined by symptoms or medication use, meaning that persistence was extremely high – much higher than what was originally thought,” Dr. Chovatiya said. “If you take a look at the literature before this study, many were retrospective analyses, and persistence was estimated to be in the 40%-60% range.”
International prospective studies have provided a more conservative estimate of persistence. For example, the German Multicenter Allergy Study followed 1,314 from birth through age 7 (J Allergy Clin Immunol. 2004;113[5]:925-31). Of these, 22% had AD within the first 2 years of life. Of these, 43% were in remission by age 3, while 38% had intermittent AD, and 19% had symptoms every year of the study. “Studies of other birth cohorts in the world came out suggesting that the rates of AD persistence ranges in the single digits to the teens,” Dr. Chovatiya said.
To reconcile these heterogeneous estimates of AD persistence, researchers conducted a systematic review and meta-analysis of 45 studies that included 110,651 subjects from 15 countries and spanned 434,992 patient-years (J Am Acad Dermatol. 2016;75:681-7.e11). They found that 80% of childhood AD had at least one observed period of disease clearance by 8 years of age. “Most importantly, less than 5% of childhood AD was persistent 20 years after diagnosis,” Dr. Chovatiya said. “However, interestingly, increased persistence was associated with later onset AD, more years of persistence, and more patient/caregiver-assessed disease.” He pointed out inherent limitations to all studies of AD persistence, including nonuniform methods of data collection, differing cohorts, different ways of diagnosing AD, different disease severity scales, and the fact that most don’t assess flares or recurrence beyond the initial period of disease clearance. “This can lead to a potential underestimation of longer-term persistence,” he said.
Childhood AD features unique predictors of persistence that may define AD trajectories. For example, in several existing studies, more persistent disease was associated with higher baseline severity, earlier-onset AD, personal history of atopy, family history of AD, AD genetic risk score (heritability, including common Filaggrin mutations), urban environment, non-White race, Hispanic ethnicity, female sex, lower household income, and overall poorer health status.
Dr. Chovatiya said. “I think that AD classification can take a lesson from asthma. When we think about how our allergy colleagues think about asthma, it is commonly classified as intermittent, mild persistent, moderate persistent, and severe persistent. Those that have intermittent disease get reactive treatment, while those with persistent disease get proactive treatment. Similarly, AD could be classified as mild intermittent, mild persistent, moderate to severe intermittent and moderate to severe persistent.”
He concluded his presentation by recommending that the fluctuating course of AD be better captured in clinical trials. “Current randomized, controlled trials use validated measures of AD signs and symptoms as inclusion criteria and measures of efficacy,” he said. “Static assessments may confound treatment effects, and assessment of prespecified time points are somewhat arbitrary in the context of disease subsets.” He proposes studies that examine aggregate measures of long-term disease control, such as number of itch-free days, weeks with clear skin, and flares experienced. “Long-term control assessment in RCTs should include signs, symptoms, health-related quality of life, and a patient global domain over time to better understand how AD is doing in the long run,” he said.
Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.
In the opinion of Raj Chovatiya, MD, PhD, the longitudinal course of atopic dermatitis (AD) is an important yet overlooked clinical domain of the disease.
“We know that AD is associated with fluctuating severity, disease flares, long-term persistence, and periods of quiescence, but its longitudinal course is not routinely incorporated into guidelines or clinical trials,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis virtual symposium. “Understanding the long-term course may improve our ability to phenotype, prognosticate, and personalize our care.”
The classic view of AD is that it starts in early childhood, follows a waxing and waning course for a few years, and burns out by adulthood. “I think we all know that this is generally false,” he said. “This was largely based on anecdotal clinical experience and large cross-sectional studies, not ones that consider the heterogeneity of AD.”
Results from a large-scale, prospective study of 7,157 children enrolled in the Pediatric Eczema Elective Registry (PEER), suggests that AD commonly persists beyond adulthood. PEER was a phase IV postmarketing safety study of children aged 12-17 with moderate to severe AD who were exposed to topical pimecrolimus and who were surveyed every 6 months (JAMA Dermatol. 2014;150[6]:593-600). The researchers found that more persistent disease was associated with self-reported disease activity, many environmental exposures, White race, history of AD, and an annual household income of less than $50,000. By age 20, 50% reported at least one 6-month symptom- and medication-free period. “The important takeaway was that at every age, greater than 80% reported active AD as defined by symptoms or medication use, meaning that persistence was extremely high – much higher than what was originally thought,” Dr. Chovatiya said. “If you take a look at the literature before this study, many were retrospective analyses, and persistence was estimated to be in the 40%-60% range.”
International prospective studies have provided a more conservative estimate of persistence. For example, the German Multicenter Allergy Study followed 1,314 from birth through age 7 (J Allergy Clin Immunol. 2004;113[5]:925-31). Of these, 22% had AD within the first 2 years of life. Of these, 43% were in remission by age 3, while 38% had intermittent AD, and 19% had symptoms every year of the study. “Studies of other birth cohorts in the world came out suggesting that the rates of AD persistence ranges in the single digits to the teens,” Dr. Chovatiya said.
To reconcile these heterogeneous estimates of AD persistence, researchers conducted a systematic review and meta-analysis of 45 studies that included 110,651 subjects from 15 countries and spanned 434,992 patient-years (J Am Acad Dermatol. 2016;75:681-7.e11). They found that 80% of childhood AD had at least one observed period of disease clearance by 8 years of age. “Most importantly, less than 5% of childhood AD was persistent 20 years after diagnosis,” Dr. Chovatiya said. “However, interestingly, increased persistence was associated with later onset AD, more years of persistence, and more patient/caregiver-assessed disease.” He pointed out inherent limitations to all studies of AD persistence, including nonuniform methods of data collection, differing cohorts, different ways of diagnosing AD, different disease severity scales, and the fact that most don’t assess flares or recurrence beyond the initial period of disease clearance. “This can lead to a potential underestimation of longer-term persistence,” he said.
Childhood AD features unique predictors of persistence that may define AD trajectories. For example, in several existing studies, more persistent disease was associated with higher baseline severity, earlier-onset AD, personal history of atopy, family history of AD, AD genetic risk score (heritability, including common Filaggrin mutations), urban environment, non-White race, Hispanic ethnicity, female sex, lower household income, and overall poorer health status.
Dr. Chovatiya said. “I think that AD classification can take a lesson from asthma. When we think about how our allergy colleagues think about asthma, it is commonly classified as intermittent, mild persistent, moderate persistent, and severe persistent. Those that have intermittent disease get reactive treatment, while those with persistent disease get proactive treatment. Similarly, AD could be classified as mild intermittent, mild persistent, moderate to severe intermittent and moderate to severe persistent.”
He concluded his presentation by recommending that the fluctuating course of AD be better captured in clinical trials. “Current randomized, controlled trials use validated measures of AD signs and symptoms as inclusion criteria and measures of efficacy,” he said. “Static assessments may confound treatment effects, and assessment of prespecified time points are somewhat arbitrary in the context of disease subsets.” He proposes studies that examine aggregate measures of long-term disease control, such as number of itch-free days, weeks with clear skin, and flares experienced. “Long-term control assessment in RCTs should include signs, symptoms, health-related quality of life, and a patient global domain over time to better understand how AD is doing in the long run,” he said.
Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.
In the opinion of Raj Chovatiya, MD, PhD, the longitudinal course of atopic dermatitis (AD) is an important yet overlooked clinical domain of the disease.
“We know that AD is associated with fluctuating severity, disease flares, long-term persistence, and periods of quiescence, but its longitudinal course is not routinely incorporated into guidelines or clinical trials,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis virtual symposium. “Understanding the long-term course may improve our ability to phenotype, prognosticate, and personalize our care.”
The classic view of AD is that it starts in early childhood, follows a waxing and waning course for a few years, and burns out by adulthood. “I think we all know that this is generally false,” he said. “This was largely based on anecdotal clinical experience and large cross-sectional studies, not ones that consider the heterogeneity of AD.”
Results from a large-scale, prospective study of 7,157 children enrolled in the Pediatric Eczema Elective Registry (PEER), suggests that AD commonly persists beyond adulthood. PEER was a phase IV postmarketing safety study of children aged 12-17 with moderate to severe AD who were exposed to topical pimecrolimus and who were surveyed every 6 months (JAMA Dermatol. 2014;150[6]:593-600). The researchers found that more persistent disease was associated with self-reported disease activity, many environmental exposures, White race, history of AD, and an annual household income of less than $50,000. By age 20, 50% reported at least one 6-month symptom- and medication-free period. “The important takeaway was that at every age, greater than 80% reported active AD as defined by symptoms or medication use, meaning that persistence was extremely high – much higher than what was originally thought,” Dr. Chovatiya said. “If you take a look at the literature before this study, many were retrospective analyses, and persistence was estimated to be in the 40%-60% range.”
International prospective studies have provided a more conservative estimate of persistence. For example, the German Multicenter Allergy Study followed 1,314 from birth through age 7 (J Allergy Clin Immunol. 2004;113[5]:925-31). Of these, 22% had AD within the first 2 years of life. Of these, 43% were in remission by age 3, while 38% had intermittent AD, and 19% had symptoms every year of the study. “Studies of other birth cohorts in the world came out suggesting that the rates of AD persistence ranges in the single digits to the teens,” Dr. Chovatiya said.
To reconcile these heterogeneous estimates of AD persistence, researchers conducted a systematic review and meta-analysis of 45 studies that included 110,651 subjects from 15 countries and spanned 434,992 patient-years (J Am Acad Dermatol. 2016;75:681-7.e11). They found that 80% of childhood AD had at least one observed period of disease clearance by 8 years of age. “Most importantly, less than 5% of childhood AD was persistent 20 years after diagnosis,” Dr. Chovatiya said. “However, interestingly, increased persistence was associated with later onset AD, more years of persistence, and more patient/caregiver-assessed disease.” He pointed out inherent limitations to all studies of AD persistence, including nonuniform methods of data collection, differing cohorts, different ways of diagnosing AD, different disease severity scales, and the fact that most don’t assess flares or recurrence beyond the initial period of disease clearance. “This can lead to a potential underestimation of longer-term persistence,” he said.
Childhood AD features unique predictors of persistence that may define AD trajectories. For example, in several existing studies, more persistent disease was associated with higher baseline severity, earlier-onset AD, personal history of atopy, family history of AD, AD genetic risk score (heritability, including common Filaggrin mutations), urban environment, non-White race, Hispanic ethnicity, female sex, lower household income, and overall poorer health status.
Dr. Chovatiya said. “I think that AD classification can take a lesson from asthma. When we think about how our allergy colleagues think about asthma, it is commonly classified as intermittent, mild persistent, moderate persistent, and severe persistent. Those that have intermittent disease get reactive treatment, while those with persistent disease get proactive treatment. Similarly, AD could be classified as mild intermittent, mild persistent, moderate to severe intermittent and moderate to severe persistent.”
He concluded his presentation by recommending that the fluctuating course of AD be better captured in clinical trials. “Current randomized, controlled trials use validated measures of AD signs and symptoms as inclusion criteria and measures of efficacy,” he said. “Static assessments may confound treatment effects, and assessment of prespecified time points are somewhat arbitrary in the context of disease subsets.” He proposes studies that examine aggregate measures of long-term disease control, such as number of itch-free days, weeks with clear skin, and flares experienced. “Long-term control assessment in RCTs should include signs, symptoms, health-related quality of life, and a patient global domain over time to better understand how AD is doing in the long run,” he said.
Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.
FROM REVOLUTIONIZING AD 2021
ACE index predicts steroid response in acute severe UC
The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*
Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.
In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.
Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.
Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.
Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).
Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.
In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.
Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.
In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.
Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.
“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”
Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.
Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.
This article was updated 1/11/22.
*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.
The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*
Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.
In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.
Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.
Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.
Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).
Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.
In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.
Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.
In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.
Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.
“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”
Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.
Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.
This article was updated 1/11/22.
*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.
The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*
Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.
In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.
Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.
Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.
Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).
Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.
In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.
Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.
In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.
Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.
“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”
Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.
Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.
This article was updated 1/11/22.
*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.
FROM AIBD 2021
Itch-dominant atopic dermatitis often flies under the radar
In the clinical experience of Jonathan I. Silverberg, MD, PhD, MPH,
That’s because a disconnect often exists between clinician-reported and patient-reported outcome measures, Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University School of Medicine and Health Sciences, said during the Revolutionizing Atopic Dermatitis virtual symposium. For example, multiple studies showed only weak to moderate correlations between the patient-focused Worst Itch Numeric Rating Scale (NRS) and Average Pruritus NRS compared with clinician-reported outcomes such as the Eczema Area and Severity Index (EASI), the objective SCORAD, body surface area (BSA), and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), with only moderate correlation coefficients ranging from 0.3 to 0.6.
“These findings suggest that clinician-reported outcome measures are poor indicators of the patient experience,” he said. “We need to do a better job capturing patient-reported outcomes to understand how patients are impacted. But there’s something more novel to this because the weak correlations may also suggest that itch and other symptoms follow a different course than the signs of the disease. Just because the lesions flare up doesn’t mean the itch does, and vice versa. Anecdotally, this came up at many patient encounters where the skin looked good, but the patient was miserable with itch.”
To understand how the combination of itch and lesion severity predicts the severity assessment, longitudinal course, burden, and treatment of AD, Dr. Silverberg and colleagues prospectively evaluated 592 adults with AD . They defined four different AD subsets using the verbal rating scale for NRS average itch combined with either the EASI, objective-SCORAD, or vIGA-AD as follows: mild-moderate itch and lesions (MI/ML), mild-moderate itch and severe lesions (MI/SL), severe itch and mild-moderate lesions (SI/ML; the itch dominant subset), and severe itch and lesions (SI/SL). They found that most patients had MI/ML (59.4%-62.3%), followed by SI/ML (21.3%-29.1%), SI/SL (6%-12.9%), and MI/SL (3.8%-6.4%). SI/ML was more common in female and Black patients.
In addition, patients with MI/SL or SI/ML described their AD as being more severe on patient global assessment and had poor quality of life (QOL) scores, while patients with SI/SL were most likely to describe their disease as severe and have poor QOL scores. Patients with SI/ML described their disease as being more severe overall, yet patients with MI/SL or SI/SL were far more likely to be assigned severe PGA scores by clinicians. “The patients who have severe itch and mild lesions consider their disease severe, but the clinician is missing it,” Dr. Silverberg said. “Occasionally they’re picking it up but they’re missing a lot of these severe itch cases when there are milder lesions.”
In other findings, patients who had baseline MI/SL, SI/ML, and SI/SL were associated with similar frequency of AD flares, periods of AD clearance/remission, more itch triggers, and longitudinal courses over time, “which is remarkable,” he said. “It means those that have severe itch, even when they have milder lesions, are going to have unstable, more persistent disease, and have a harder time keeping control of it, and are ultimately going to require systemic therapies.” In fact, most patients with SI/SL (57.8%-66.7%) and MI/SL (53.9%-57.7%) but fewer patients with MI/ML (36.7%-38.4%) and SI/ML (30.8%-32%) initiated systemic, biologic, or phototherapy for their AD during follow-up. “There is a real upshot here clinically, in that patients are just not getting stepped up appropriately to achieve better control of their disease when they have itch-dominant AD,” Dr. Silverberg said.
He described itch-dominant AD as a novel disease phenotype that requires further investigation. “Why is it that some patients are getting such severe itch and milder looking lesions?” he asked. “I don’t think it’s just a matter of poor outcome measures that we have. So, what is it? It’s not entirely clear. Clinically, itch-dominant AD is important as it relates to the issues of diversity and skin of color because in darker skin tones, we cannot easily appreciate erythema. We may totally miss the active lesions. I think that’s a big part of why we see this itch-dominant AD more commonly in Black patients. Therefore, it is so important to ask our patients about their symptoms and to assess the severity of itch. But, even if they have what we think are milder lesions and severe itch, we must recognize they may not be well controlled. They may not be happy. They may have poor quality of life, and they may need to be stepped up appropriately. We need a lot more information to guide the assessment and management of this important subset of patients.”
Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma.
In the clinical experience of Jonathan I. Silverberg, MD, PhD, MPH,
That’s because a disconnect often exists between clinician-reported and patient-reported outcome measures, Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University School of Medicine and Health Sciences, said during the Revolutionizing Atopic Dermatitis virtual symposium. For example, multiple studies showed only weak to moderate correlations between the patient-focused Worst Itch Numeric Rating Scale (NRS) and Average Pruritus NRS compared with clinician-reported outcomes such as the Eczema Area and Severity Index (EASI), the objective SCORAD, body surface area (BSA), and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), with only moderate correlation coefficients ranging from 0.3 to 0.6.
“These findings suggest that clinician-reported outcome measures are poor indicators of the patient experience,” he said. “We need to do a better job capturing patient-reported outcomes to understand how patients are impacted. But there’s something more novel to this because the weak correlations may also suggest that itch and other symptoms follow a different course than the signs of the disease. Just because the lesions flare up doesn’t mean the itch does, and vice versa. Anecdotally, this came up at many patient encounters where the skin looked good, but the patient was miserable with itch.”
To understand how the combination of itch and lesion severity predicts the severity assessment, longitudinal course, burden, and treatment of AD, Dr. Silverberg and colleagues prospectively evaluated 592 adults with AD . They defined four different AD subsets using the verbal rating scale for NRS average itch combined with either the EASI, objective-SCORAD, or vIGA-AD as follows: mild-moderate itch and lesions (MI/ML), mild-moderate itch and severe lesions (MI/SL), severe itch and mild-moderate lesions (SI/ML; the itch dominant subset), and severe itch and lesions (SI/SL). They found that most patients had MI/ML (59.4%-62.3%), followed by SI/ML (21.3%-29.1%), SI/SL (6%-12.9%), and MI/SL (3.8%-6.4%). SI/ML was more common in female and Black patients.
In addition, patients with MI/SL or SI/ML described their AD as being more severe on patient global assessment and had poor quality of life (QOL) scores, while patients with SI/SL were most likely to describe their disease as severe and have poor QOL scores. Patients with SI/ML described their disease as being more severe overall, yet patients with MI/SL or SI/SL were far more likely to be assigned severe PGA scores by clinicians. “The patients who have severe itch and mild lesions consider their disease severe, but the clinician is missing it,” Dr. Silverberg said. “Occasionally they’re picking it up but they’re missing a lot of these severe itch cases when there are milder lesions.”
In other findings, patients who had baseline MI/SL, SI/ML, and SI/SL were associated with similar frequency of AD flares, periods of AD clearance/remission, more itch triggers, and longitudinal courses over time, “which is remarkable,” he said. “It means those that have severe itch, even when they have milder lesions, are going to have unstable, more persistent disease, and have a harder time keeping control of it, and are ultimately going to require systemic therapies.” In fact, most patients with SI/SL (57.8%-66.7%) and MI/SL (53.9%-57.7%) but fewer patients with MI/ML (36.7%-38.4%) and SI/ML (30.8%-32%) initiated systemic, biologic, or phototherapy for their AD during follow-up. “There is a real upshot here clinically, in that patients are just not getting stepped up appropriately to achieve better control of their disease when they have itch-dominant AD,” Dr. Silverberg said.
He described itch-dominant AD as a novel disease phenotype that requires further investigation. “Why is it that some patients are getting such severe itch and milder looking lesions?” he asked. “I don’t think it’s just a matter of poor outcome measures that we have. So, what is it? It’s not entirely clear. Clinically, itch-dominant AD is important as it relates to the issues of diversity and skin of color because in darker skin tones, we cannot easily appreciate erythema. We may totally miss the active lesions. I think that’s a big part of why we see this itch-dominant AD more commonly in Black patients. Therefore, it is so important to ask our patients about their symptoms and to assess the severity of itch. But, even if they have what we think are milder lesions and severe itch, we must recognize they may not be well controlled. They may not be happy. They may have poor quality of life, and they may need to be stepped up appropriately. We need a lot more information to guide the assessment and management of this important subset of patients.”
Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma.
In the clinical experience of Jonathan I. Silverberg, MD, PhD, MPH,
That’s because a disconnect often exists between clinician-reported and patient-reported outcome measures, Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University School of Medicine and Health Sciences, said during the Revolutionizing Atopic Dermatitis virtual symposium. For example, multiple studies showed only weak to moderate correlations between the patient-focused Worst Itch Numeric Rating Scale (NRS) and Average Pruritus NRS compared with clinician-reported outcomes such as the Eczema Area and Severity Index (EASI), the objective SCORAD, body surface area (BSA), and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), with only moderate correlation coefficients ranging from 0.3 to 0.6.
“These findings suggest that clinician-reported outcome measures are poor indicators of the patient experience,” he said. “We need to do a better job capturing patient-reported outcomes to understand how patients are impacted. But there’s something more novel to this because the weak correlations may also suggest that itch and other symptoms follow a different course than the signs of the disease. Just because the lesions flare up doesn’t mean the itch does, and vice versa. Anecdotally, this came up at many patient encounters where the skin looked good, but the patient was miserable with itch.”
To understand how the combination of itch and lesion severity predicts the severity assessment, longitudinal course, burden, and treatment of AD, Dr. Silverberg and colleagues prospectively evaluated 592 adults with AD . They defined four different AD subsets using the verbal rating scale for NRS average itch combined with either the EASI, objective-SCORAD, or vIGA-AD as follows: mild-moderate itch and lesions (MI/ML), mild-moderate itch and severe lesions (MI/SL), severe itch and mild-moderate lesions (SI/ML; the itch dominant subset), and severe itch and lesions (SI/SL). They found that most patients had MI/ML (59.4%-62.3%), followed by SI/ML (21.3%-29.1%), SI/SL (6%-12.9%), and MI/SL (3.8%-6.4%). SI/ML was more common in female and Black patients.
In addition, patients with MI/SL or SI/ML described their AD as being more severe on patient global assessment and had poor quality of life (QOL) scores, while patients with SI/SL were most likely to describe their disease as severe and have poor QOL scores. Patients with SI/ML described their disease as being more severe overall, yet patients with MI/SL or SI/SL were far more likely to be assigned severe PGA scores by clinicians. “The patients who have severe itch and mild lesions consider their disease severe, but the clinician is missing it,” Dr. Silverberg said. “Occasionally they’re picking it up but they’re missing a lot of these severe itch cases when there are milder lesions.”
In other findings, patients who had baseline MI/SL, SI/ML, and SI/SL were associated with similar frequency of AD flares, periods of AD clearance/remission, more itch triggers, and longitudinal courses over time, “which is remarkable,” he said. “It means those that have severe itch, even when they have milder lesions, are going to have unstable, more persistent disease, and have a harder time keeping control of it, and are ultimately going to require systemic therapies.” In fact, most patients with SI/SL (57.8%-66.7%) and MI/SL (53.9%-57.7%) but fewer patients with MI/ML (36.7%-38.4%) and SI/ML (30.8%-32%) initiated systemic, biologic, or phototherapy for their AD during follow-up. “There is a real upshot here clinically, in that patients are just not getting stepped up appropriately to achieve better control of their disease when they have itch-dominant AD,” Dr. Silverberg said.
He described itch-dominant AD as a novel disease phenotype that requires further investigation. “Why is it that some patients are getting such severe itch and milder looking lesions?” he asked. “I don’t think it’s just a matter of poor outcome measures that we have. So, what is it? It’s not entirely clear. Clinically, itch-dominant AD is important as it relates to the issues of diversity and skin of color because in darker skin tones, we cannot easily appreciate erythema. We may totally miss the active lesions. I think that’s a big part of why we see this itch-dominant AD more commonly in Black patients. Therefore, it is so important to ask our patients about their symptoms and to assess the severity of itch. But, even if they have what we think are milder lesions and severe itch, we must recognize they may not be well controlled. They may not be happy. They may have poor quality of life, and they may need to be stepped up appropriately. We need a lot more information to guide the assessment and management of this important subset of patients.”
Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma.
FROM REVOLUTIONIZING AD 2021
Atopic dermatitis can be especially burdensome in the elderly
During the Revolutionizing Atopic Dermatitis virtual symposium, Katrina Abuabara, MD, highlighted the epidemiology and burden of AD among older adults. She began by noting that the disease peaks in infancy and older adulthood. In an analysis that she and her colleagues made of physician-diagnosed AD among more than 8.6 million patients in the United Kingdom between 1994 and 2013, the mean prevalence in a given year was 12.3% among those aged 0-17 years, 5.1% among those age 18-74 years, and 8.7% among those age 75 and older.
“We saw what we expected in early infancy with very high rates of active disease,” said Dr. Abuabara, associate professor of dermatology and epidemiology at the University of California, San Francisco. “We also saw a second peak in older adulthood. This was more surprising to us because the disease hadn’t been as well studied in this population.” Researchers who analyzed data from the Global Burden of Disease Study, which evaluates disease-related morbidity and mortality worldwide, found a somewhat attenuated peak but a similar trend around the world. Its authors ranked AD as 15th among all nonfatal diseases.
In a separate analysis, Dr. Abuabara and colleagues evaluated records of more than 9.1 million primary care patients in the United Kingdom between 1994 and 2013, and who were followed for an average of 6 years. They examined AD activity and found that, based on doctor visits and prescriptions, AD appeared to be active in 48% of those aged 0-17 years, compared with 42% of those aged 18-74 years, and 60% of those aged 75 years and older. “Also, when we looked at the distribution of active disease in older adults, we saw that those who were older had more severe disease,” she said. When they evaluated the prevalence of AD by sociodemographic factors, AD increased with age among older adults (adjusted odd ratio, 1.06), while it decreased by 14% annually among children. In addition, female older adults had about three-fourths the odds of prevalent disease as their male counterparts (aOR, 0.73).
“We also looked at rural and urban differences and found that across ages it was more common in urban as compared to rural populations,” she said. “As for socioeconomic status, it tends to be more common among those of higher socioeconomic status in children and in the older adult group.”
In a study that drew from medical records of 3.85 million primary care patients in the United Kingdom, AD was more common in Asian and Black ethnic groups than in people of White ethnicity. In addition, higher socioeconomic status was associated with a greater incidence of eczema in infants aged younger than 2 years, but the reverse was seen for all other age groups.
To identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, Dr. Abuabara and colleagues evaluated members of two population-based birth cohorts: the 1958 National Childhood Development Study and the 1970 British Cohort Study. The patients were classified into one of four patters of disease activity followed to age 50: rare/none, increasing, decreasing, and high. “We found that there was the early-onset decreasing subgroup, which tend to have a lower probability of AD over time,” Dr. Abuabara said. “We also found that there was a small subgroup that had a constant high probability of AD over time. But we were surprised to find a subgroup with increasing probability over time. This was a fairly sizable subgroup.”
In an earlier study, she and her colleagues examined whether there were differences based on whether people had adult-onset or childhood-onset disease in the same two cohorts of U.K. patients. Those with childhood-onset disease had stronger associations with known genetic risk factors and they tended to be of higher socioeconomic status. “They also tended to have more asthma and other allergic comorbidities,” Dr. Abuabara said. “On the other hand, the adult-onset group [after age 23] were more likely to be female, more likely to be smokers, and tended to have lower childhood socioeconomic status.”
According to the best available evidence, she continued, there is good data on higher relative risk of osteoporosis/fractures and dementia specifically among older adults with AD, and good data on associations with cardiometabolic disease and atopic disease among adults overall, as well as data showing that AD does not seem to be associated with cancer overall. In a study conducted by Jonathan I. Silverberg, MD, PhD, MPH, and Mohammed S. Shaheen, JD, the researchers used physician-diagnosed AD to investigate the associations of osteopenia and osteoporosis in two large U.S. databases: the 2006-2012 Nationwide Emergency Department Sample (NEDS) database and 2002-2012 National Inpatient Sample (NIS). Among patients aged 50 years and older, AD was associated with a higher odds of osteoporosis in NEDS (aOR, 1.31) and NIS (aOR, 1.25) and osteopenia in NEDS (aOR, 1.86).
In a separate matched cohort study, Dr. Abuabara and colleagues used U.K. primary care patient data to evaluate the association between AD and fracture and whether fracture risk varies with AD severity. Overall, they observed a 10% increase in fracture risk among people with AD, compared with those without, especially those of the hip, spine, pelvis, and wrist. “We found that there was a dose-response effect,” she said. “Those with more severe eczema had a much higher risk of fractures. When we looked at different age groups, we found a similar increased risk in the oldest adults as in younger adults.”
In a longitudinal cohort study of primary care medical records from more than 1.1 million individuals in the United Kingdom, AD was associated with an increased risk of vascular dementia (hazard ratio, 1.88), Alzheimer’s disease (HR, 1.69, and other/unspecified dementia (HR, 1.48; .269). “We found a nice dose response, where people with more severe AD had higher rates of dementia,” Dr. Abuabara said. Results from a more recent, smaller study of patients in Taiwan also found an increased risk between AD and the risk of dementia, but not a dose-response effect, likely because of a much smaller sample size.
Mounting research suggests that the risk for cardiovascular disease is also elevated in patients with AD. “There is some variability in the literature, but I think it’s important that when we’re talking about atopic dermatitis to think about the heterogeneity of the disease,” Dr. Abuabara said. In a meta-analysis and systematic review of 19 studies on the topic, she and her colleagues found that AD was associated with an increased risk of myocardial infarction (relative risk, 1.12), stroke (RR, 1.10), ischemic stroke (RR, 1.17), angina (RR, 1.18), and heart failure (RR, 1.26). “For all the different [cardiovascular disease] outcomes there was increasing risk with increasing disease severity,” she said.
She reported that UCSF receives research funding from Pfizer and Cosmetique Active International. She also receives consulting fees from Target RWE.
During the Revolutionizing Atopic Dermatitis virtual symposium, Katrina Abuabara, MD, highlighted the epidemiology and burden of AD among older adults. She began by noting that the disease peaks in infancy and older adulthood. In an analysis that she and her colleagues made of physician-diagnosed AD among more than 8.6 million patients in the United Kingdom between 1994 and 2013, the mean prevalence in a given year was 12.3% among those aged 0-17 years, 5.1% among those age 18-74 years, and 8.7% among those age 75 and older.
“We saw what we expected in early infancy with very high rates of active disease,” said Dr. Abuabara, associate professor of dermatology and epidemiology at the University of California, San Francisco. “We also saw a second peak in older adulthood. This was more surprising to us because the disease hadn’t been as well studied in this population.” Researchers who analyzed data from the Global Burden of Disease Study, which evaluates disease-related morbidity and mortality worldwide, found a somewhat attenuated peak but a similar trend around the world. Its authors ranked AD as 15th among all nonfatal diseases.
In a separate analysis, Dr. Abuabara and colleagues evaluated records of more than 9.1 million primary care patients in the United Kingdom between 1994 and 2013, and who were followed for an average of 6 years. They examined AD activity and found that, based on doctor visits and prescriptions, AD appeared to be active in 48% of those aged 0-17 years, compared with 42% of those aged 18-74 years, and 60% of those aged 75 years and older. “Also, when we looked at the distribution of active disease in older adults, we saw that those who were older had more severe disease,” she said. When they evaluated the prevalence of AD by sociodemographic factors, AD increased with age among older adults (adjusted odd ratio, 1.06), while it decreased by 14% annually among children. In addition, female older adults had about three-fourths the odds of prevalent disease as their male counterparts (aOR, 0.73).
“We also looked at rural and urban differences and found that across ages it was more common in urban as compared to rural populations,” she said. “As for socioeconomic status, it tends to be more common among those of higher socioeconomic status in children and in the older adult group.”
In a study that drew from medical records of 3.85 million primary care patients in the United Kingdom, AD was more common in Asian and Black ethnic groups than in people of White ethnicity. In addition, higher socioeconomic status was associated with a greater incidence of eczema in infants aged younger than 2 years, but the reverse was seen for all other age groups.
To identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, Dr. Abuabara and colleagues evaluated members of two population-based birth cohorts: the 1958 National Childhood Development Study and the 1970 British Cohort Study. The patients were classified into one of four patters of disease activity followed to age 50: rare/none, increasing, decreasing, and high. “We found that there was the early-onset decreasing subgroup, which tend to have a lower probability of AD over time,” Dr. Abuabara said. “We also found that there was a small subgroup that had a constant high probability of AD over time. But we were surprised to find a subgroup with increasing probability over time. This was a fairly sizable subgroup.”
In an earlier study, she and her colleagues examined whether there were differences based on whether people had adult-onset or childhood-onset disease in the same two cohorts of U.K. patients. Those with childhood-onset disease had stronger associations with known genetic risk factors and they tended to be of higher socioeconomic status. “They also tended to have more asthma and other allergic comorbidities,” Dr. Abuabara said. “On the other hand, the adult-onset group [after age 23] were more likely to be female, more likely to be smokers, and tended to have lower childhood socioeconomic status.”
According to the best available evidence, she continued, there is good data on higher relative risk of osteoporosis/fractures and dementia specifically among older adults with AD, and good data on associations with cardiometabolic disease and atopic disease among adults overall, as well as data showing that AD does not seem to be associated with cancer overall. In a study conducted by Jonathan I. Silverberg, MD, PhD, MPH, and Mohammed S. Shaheen, JD, the researchers used physician-diagnosed AD to investigate the associations of osteopenia and osteoporosis in two large U.S. databases: the 2006-2012 Nationwide Emergency Department Sample (NEDS) database and 2002-2012 National Inpatient Sample (NIS). Among patients aged 50 years and older, AD was associated with a higher odds of osteoporosis in NEDS (aOR, 1.31) and NIS (aOR, 1.25) and osteopenia in NEDS (aOR, 1.86).
In a separate matched cohort study, Dr. Abuabara and colleagues used U.K. primary care patient data to evaluate the association between AD and fracture and whether fracture risk varies with AD severity. Overall, they observed a 10% increase in fracture risk among people with AD, compared with those without, especially those of the hip, spine, pelvis, and wrist. “We found that there was a dose-response effect,” she said. “Those with more severe eczema had a much higher risk of fractures. When we looked at different age groups, we found a similar increased risk in the oldest adults as in younger adults.”
In a longitudinal cohort study of primary care medical records from more than 1.1 million individuals in the United Kingdom, AD was associated with an increased risk of vascular dementia (hazard ratio, 1.88), Alzheimer’s disease (HR, 1.69, and other/unspecified dementia (HR, 1.48; .269). “We found a nice dose response, where people with more severe AD had higher rates of dementia,” Dr. Abuabara said. Results from a more recent, smaller study of patients in Taiwan also found an increased risk between AD and the risk of dementia, but not a dose-response effect, likely because of a much smaller sample size.
Mounting research suggests that the risk for cardiovascular disease is also elevated in patients with AD. “There is some variability in the literature, but I think it’s important that when we’re talking about atopic dermatitis to think about the heterogeneity of the disease,” Dr. Abuabara said. In a meta-analysis and systematic review of 19 studies on the topic, she and her colleagues found that AD was associated with an increased risk of myocardial infarction (relative risk, 1.12), stroke (RR, 1.10), ischemic stroke (RR, 1.17), angina (RR, 1.18), and heart failure (RR, 1.26). “For all the different [cardiovascular disease] outcomes there was increasing risk with increasing disease severity,” she said.
She reported that UCSF receives research funding from Pfizer and Cosmetique Active International. She also receives consulting fees from Target RWE.
During the Revolutionizing Atopic Dermatitis virtual symposium, Katrina Abuabara, MD, highlighted the epidemiology and burden of AD among older adults. She began by noting that the disease peaks in infancy and older adulthood. In an analysis that she and her colleagues made of physician-diagnosed AD among more than 8.6 million patients in the United Kingdom between 1994 and 2013, the mean prevalence in a given year was 12.3% among those aged 0-17 years, 5.1% among those age 18-74 years, and 8.7% among those age 75 and older.
“We saw what we expected in early infancy with very high rates of active disease,” said Dr. Abuabara, associate professor of dermatology and epidemiology at the University of California, San Francisco. “We also saw a second peak in older adulthood. This was more surprising to us because the disease hadn’t been as well studied in this population.” Researchers who analyzed data from the Global Burden of Disease Study, which evaluates disease-related morbidity and mortality worldwide, found a somewhat attenuated peak but a similar trend around the world. Its authors ranked AD as 15th among all nonfatal diseases.
In a separate analysis, Dr. Abuabara and colleagues evaluated records of more than 9.1 million primary care patients in the United Kingdom between 1994 and 2013, and who were followed for an average of 6 years. They examined AD activity and found that, based on doctor visits and prescriptions, AD appeared to be active in 48% of those aged 0-17 years, compared with 42% of those aged 18-74 years, and 60% of those aged 75 years and older. “Also, when we looked at the distribution of active disease in older adults, we saw that those who were older had more severe disease,” she said. When they evaluated the prevalence of AD by sociodemographic factors, AD increased with age among older adults (adjusted odd ratio, 1.06), while it decreased by 14% annually among children. In addition, female older adults had about three-fourths the odds of prevalent disease as their male counterparts (aOR, 0.73).
“We also looked at rural and urban differences and found that across ages it was more common in urban as compared to rural populations,” she said. “As for socioeconomic status, it tends to be more common among those of higher socioeconomic status in children and in the older adult group.”
In a study that drew from medical records of 3.85 million primary care patients in the United Kingdom, AD was more common in Asian and Black ethnic groups than in people of White ethnicity. In addition, higher socioeconomic status was associated with a greater incidence of eczema in infants aged younger than 2 years, but the reverse was seen for all other age groups.
To identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, Dr. Abuabara and colleagues evaluated members of two population-based birth cohorts: the 1958 National Childhood Development Study and the 1970 British Cohort Study. The patients were classified into one of four patters of disease activity followed to age 50: rare/none, increasing, decreasing, and high. “We found that there was the early-onset decreasing subgroup, which tend to have a lower probability of AD over time,” Dr. Abuabara said. “We also found that there was a small subgroup that had a constant high probability of AD over time. But we were surprised to find a subgroup with increasing probability over time. This was a fairly sizable subgroup.”
In an earlier study, she and her colleagues examined whether there were differences based on whether people had adult-onset or childhood-onset disease in the same two cohorts of U.K. patients. Those with childhood-onset disease had stronger associations with known genetic risk factors and they tended to be of higher socioeconomic status. “They also tended to have more asthma and other allergic comorbidities,” Dr. Abuabara said. “On the other hand, the adult-onset group [after age 23] were more likely to be female, more likely to be smokers, and tended to have lower childhood socioeconomic status.”
According to the best available evidence, she continued, there is good data on higher relative risk of osteoporosis/fractures and dementia specifically among older adults with AD, and good data on associations with cardiometabolic disease and atopic disease among adults overall, as well as data showing that AD does not seem to be associated with cancer overall. In a study conducted by Jonathan I. Silverberg, MD, PhD, MPH, and Mohammed S. Shaheen, JD, the researchers used physician-diagnosed AD to investigate the associations of osteopenia and osteoporosis in two large U.S. databases: the 2006-2012 Nationwide Emergency Department Sample (NEDS) database and 2002-2012 National Inpatient Sample (NIS). Among patients aged 50 years and older, AD was associated with a higher odds of osteoporosis in NEDS (aOR, 1.31) and NIS (aOR, 1.25) and osteopenia in NEDS (aOR, 1.86).
In a separate matched cohort study, Dr. Abuabara and colleagues used U.K. primary care patient data to evaluate the association between AD and fracture and whether fracture risk varies with AD severity. Overall, they observed a 10% increase in fracture risk among people with AD, compared with those without, especially those of the hip, spine, pelvis, and wrist. “We found that there was a dose-response effect,” she said. “Those with more severe eczema had a much higher risk of fractures. When we looked at different age groups, we found a similar increased risk in the oldest adults as in younger adults.”
In a longitudinal cohort study of primary care medical records from more than 1.1 million individuals in the United Kingdom, AD was associated with an increased risk of vascular dementia (hazard ratio, 1.88), Alzheimer’s disease (HR, 1.69, and other/unspecified dementia (HR, 1.48; .269). “We found a nice dose response, where people with more severe AD had higher rates of dementia,” Dr. Abuabara said. Results from a more recent, smaller study of patients in Taiwan also found an increased risk between AD and the risk of dementia, but not a dose-response effect, likely because of a much smaller sample size.
Mounting research suggests that the risk for cardiovascular disease is also elevated in patients with AD. “There is some variability in the literature, but I think it’s important that when we’re talking about atopic dermatitis to think about the heterogeneity of the disease,” Dr. Abuabara said. In a meta-analysis and systematic review of 19 studies on the topic, she and her colleagues found that AD was associated with an increased risk of myocardial infarction (relative risk, 1.12), stroke (RR, 1.10), ischemic stroke (RR, 1.17), angina (RR, 1.18), and heart failure (RR, 1.26). “For all the different [cardiovascular disease] outcomes there was increasing risk with increasing disease severity,” she said.
She reported that UCSF receives research funding from Pfizer and Cosmetique Active International. She also receives consulting fees from Target RWE.
FROM REVOLUTIONIZING AD 2021
Vedolizumab does not increase risk of C. diff infection in UC
Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.
Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.
In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.
These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.
In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.
The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).
Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.
Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.
In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.
“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
Recurrence worries
Recurrent CDI is an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.
Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.
“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”
Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.
Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff .
Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.
Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.
In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.
These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.
In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.
The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).
Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.
Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.
In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.
“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
Recurrence worries
Recurrent CDI is an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.
Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.
“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”
Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.
Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff .
Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.
Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.
In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.
These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.
In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.
The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).
Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.
Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.
In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.
“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
Recurrence worries
Recurrent CDI is an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.
Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.
“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”
Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.
Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff .
FROM AIBD 2021
Breast cancer treatment worse for incarcerated patients
The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).
Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.
They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.
“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.
Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”
Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”
The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”
Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.
Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.
The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).
“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.
No funding or relevant financial relationships were declared for this featured study.
The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).
Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.
They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.
“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.
Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”
Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”
The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”
Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.
Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.
The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).
“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.
No funding or relevant financial relationships were declared for this featured study.
The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).
Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.
They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.
“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.
Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”
Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”
The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”
Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.
Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.
The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).
“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.
No funding or relevant financial relationships were declared for this featured study.
FROM SABCS 2021
Seventeen percent of breast cancer patients reclassified after risk score reassessment
Elisha Hughes, PhD, director of research biostatistics at Myriad Genetics (which funded the study), and colleagues combined a risk model containing 149 single-nucleotide polymorphisms (SNPs), of which just over one-third were related to genetic ancestry, with the Tyrer-Cuzick (TC) breast cancer risk model.
The resulting combined risk score, which was developed in a cohort of over 145,000 women and validated in another group of almost 69,000 women, was not only well calibrated, but also able to reclassify just over 17% of women into a different risk group versus the clinical model.
The research (abstract P2-11-21) was presented at the San Antonio Breast Cancer Symposium on Dec. 8.
“This is the first breast cancer risk model based on a polygenic score, the 149-SNP PRS, that incorporates genetically determined ancestral composition and is validated for diverse ancestries,” the team reported.
The combined model substantially improved risk stratification over TC alone and may “lead to enhanced breast cancer risk reduction strategies, such as increased surveillance and use of preventive medications,” the researchers reported.
Breast cancer has a substantial genetic component that can “inform risk prediction and personalized preventive measures.” However, polygenic risk scores are largely derived from studies of women of European descent and tend to have poor performance in non-European ancestries.
Combined score substantially improved risk stratification over TC alone
The research team developed a polygenic risk score based on 149 SNPs for women of diverse backgrounds who did not have pathologic variants in breast cancer susceptibility genes, and included 56 ancestry-informative variants with 93 BC-associated variants. They combined the 149-SNP polygenic risk score with the TC risk model to create a combined risk score that was developed in a cohort of 145,786 women who were unaffected by breast cancer, following a fixed-stratified model to avoid double counting between confounded factors.
Of the women included in the cohort, 69.1% were of European descent, while 10.2% were Hispanic, 10.0% Black/African, 1.9% Asian, and 8.8% all other groups.
An independent cohort of 68,803 women of a similar ethnic distribution was then used to evaluate the calibration of the combined risk score against the TC risk model alone, and to examine the relative contributions of the 149-SNP PRS, family history, and other clinical factors.
The results showed that, overall, the combined risk score was well calibrated across ancestries and percentiles of risks, and the absolute lifetime risks were similar to those derived from the TC risk model alone. The only exception was Hispanic carriers of a protective Amerindian SNP who had a lower score on the combined risk score than the TC model.
Using an ANOVA model, the team found that family history contributed 48% to the lifetime risk of breast cancer, while the 149-SNP PRS contributed 35% and other factors 17%. Family history was weakly, but significantly correlated with the 149-SNP PRS.
Determining the impact of adding the 149-SNP PRS to the TC risk model on risk classification, the team showed that across all ancestries, 17.3% of women were reclassified by the combined risk score versus the TC model alone, with 10.8% having their lifetime risk increased to high risk and 29.1% having their risk decreased by the combined model to low risk.
The largest reclassifications were seen for women of European descent, while the smallest were for Black/African women.
Study may have ‘cracked the code’
“What’s exciting is that I think we kind-of ‘cracked the code’ to some extent of how to do this across diseases for all ancestries,” Thomas P. Slavin, MD, chief medical officer at Myriad Genetics, said in an interview. “The adaptation for breast cancer risk stratification and the new panel [is] for breast cancer across all ancestries, but what we developed is something that could be used across diabetes, or colon cancer, or anything.”
He explained that they realized that “for each one of these little hot spots” in the SNPs, “that make one person different from another, you really need to find out where in the world that originated from. So, if you have genetic ancestry on an individual, you can say this spot in the genome has more of an African ancestry to it, or a European ancestry, and then you can weight it appropriately by the population.”
Dr. Slavin said that standard PRSs that simply add up SNPs are “pretty good” and “add a lot” to risk stratification, “but to fine-tune it a little bit and make the best risk model, you really do need to bring in clinical and family history factors.”
Montserrat García-Closas, MD, DrPH, deputy director of the cancer epidemiology and genetics for the National Cancer Institute, said the study is of interest, but “does not give information on how ancestry was considered in the models used to derive the scores.” She also cautioned that the method used in the study to calibrate the model seems “to mean a comparison of scores, rather than comparing the observed and expected risk in prospective cohorts by ancestry groups. This would be a way to estimate bias in risk prediction by ancestry.”
Nevertheless, Dr. García-Closas said the degree of risk reclassification seen with the combined risk score is as expected and pointed to recent work by her and her colleagues in which they tested an integrated model incorporating classical risk factors and a 313-variant PRS to predict breast-cancer risk and achieved similar results.
Several study authors disclosed ties with Myriad Genetics, as well as AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Helix BioPharma, Konica Minolta, Ambry Genetics, Invitae, Stryker, GAIL, Phenogen Sciences, Novartis, Pfizer, CancerIQ, Tempus, 54gene, Color Genetics, Roche/Genentech, ImpediMed, Prelude Therapeutics, BD, Agendia, Targeted Medical Education, Cerebrotech Medical Systems, Integra LifeSciences, Puma Biotechnology, GeneDX/BioReference, Change Health Care, Research to Practice, Clinical Care Options, Physician Education Resource, and Daiichi Sankyo.
The headline for this article was updated on 1/6/22.
Elisha Hughes, PhD, director of research biostatistics at Myriad Genetics (which funded the study), and colleagues combined a risk model containing 149 single-nucleotide polymorphisms (SNPs), of which just over one-third were related to genetic ancestry, with the Tyrer-Cuzick (TC) breast cancer risk model.
The resulting combined risk score, which was developed in a cohort of over 145,000 women and validated in another group of almost 69,000 women, was not only well calibrated, but also able to reclassify just over 17% of women into a different risk group versus the clinical model.
The research (abstract P2-11-21) was presented at the San Antonio Breast Cancer Symposium on Dec. 8.
“This is the first breast cancer risk model based on a polygenic score, the 149-SNP PRS, that incorporates genetically determined ancestral composition and is validated for diverse ancestries,” the team reported.
The combined model substantially improved risk stratification over TC alone and may “lead to enhanced breast cancer risk reduction strategies, such as increased surveillance and use of preventive medications,” the researchers reported.
Breast cancer has a substantial genetic component that can “inform risk prediction and personalized preventive measures.” However, polygenic risk scores are largely derived from studies of women of European descent and tend to have poor performance in non-European ancestries.
Combined score substantially improved risk stratification over TC alone
The research team developed a polygenic risk score based on 149 SNPs for women of diverse backgrounds who did not have pathologic variants in breast cancer susceptibility genes, and included 56 ancestry-informative variants with 93 BC-associated variants. They combined the 149-SNP polygenic risk score with the TC risk model to create a combined risk score that was developed in a cohort of 145,786 women who were unaffected by breast cancer, following a fixed-stratified model to avoid double counting between confounded factors.
Of the women included in the cohort, 69.1% were of European descent, while 10.2% were Hispanic, 10.0% Black/African, 1.9% Asian, and 8.8% all other groups.
An independent cohort of 68,803 women of a similar ethnic distribution was then used to evaluate the calibration of the combined risk score against the TC risk model alone, and to examine the relative contributions of the 149-SNP PRS, family history, and other clinical factors.
The results showed that, overall, the combined risk score was well calibrated across ancestries and percentiles of risks, and the absolute lifetime risks were similar to those derived from the TC risk model alone. The only exception was Hispanic carriers of a protective Amerindian SNP who had a lower score on the combined risk score than the TC model.
Using an ANOVA model, the team found that family history contributed 48% to the lifetime risk of breast cancer, while the 149-SNP PRS contributed 35% and other factors 17%. Family history was weakly, but significantly correlated with the 149-SNP PRS.
Determining the impact of adding the 149-SNP PRS to the TC risk model on risk classification, the team showed that across all ancestries, 17.3% of women were reclassified by the combined risk score versus the TC model alone, with 10.8% having their lifetime risk increased to high risk and 29.1% having their risk decreased by the combined model to low risk.
The largest reclassifications were seen for women of European descent, while the smallest were for Black/African women.
Study may have ‘cracked the code’
“What’s exciting is that I think we kind-of ‘cracked the code’ to some extent of how to do this across diseases for all ancestries,” Thomas P. Slavin, MD, chief medical officer at Myriad Genetics, said in an interview. “The adaptation for breast cancer risk stratification and the new panel [is] for breast cancer across all ancestries, but what we developed is something that could be used across diabetes, or colon cancer, or anything.”
He explained that they realized that “for each one of these little hot spots” in the SNPs, “that make one person different from another, you really need to find out where in the world that originated from. So, if you have genetic ancestry on an individual, you can say this spot in the genome has more of an African ancestry to it, or a European ancestry, and then you can weight it appropriately by the population.”
Dr. Slavin said that standard PRSs that simply add up SNPs are “pretty good” and “add a lot” to risk stratification, “but to fine-tune it a little bit and make the best risk model, you really do need to bring in clinical and family history factors.”
Montserrat García-Closas, MD, DrPH, deputy director of the cancer epidemiology and genetics for the National Cancer Institute, said the study is of interest, but “does not give information on how ancestry was considered in the models used to derive the scores.” She also cautioned that the method used in the study to calibrate the model seems “to mean a comparison of scores, rather than comparing the observed and expected risk in prospective cohorts by ancestry groups. This would be a way to estimate bias in risk prediction by ancestry.”
Nevertheless, Dr. García-Closas said the degree of risk reclassification seen with the combined risk score is as expected and pointed to recent work by her and her colleagues in which they tested an integrated model incorporating classical risk factors and a 313-variant PRS to predict breast-cancer risk and achieved similar results.
Several study authors disclosed ties with Myriad Genetics, as well as AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Helix BioPharma, Konica Minolta, Ambry Genetics, Invitae, Stryker, GAIL, Phenogen Sciences, Novartis, Pfizer, CancerIQ, Tempus, 54gene, Color Genetics, Roche/Genentech, ImpediMed, Prelude Therapeutics, BD, Agendia, Targeted Medical Education, Cerebrotech Medical Systems, Integra LifeSciences, Puma Biotechnology, GeneDX/BioReference, Change Health Care, Research to Practice, Clinical Care Options, Physician Education Resource, and Daiichi Sankyo.
The headline for this article was updated on 1/6/22.
Elisha Hughes, PhD, director of research biostatistics at Myriad Genetics (which funded the study), and colleagues combined a risk model containing 149 single-nucleotide polymorphisms (SNPs), of which just over one-third were related to genetic ancestry, with the Tyrer-Cuzick (TC) breast cancer risk model.
The resulting combined risk score, which was developed in a cohort of over 145,000 women and validated in another group of almost 69,000 women, was not only well calibrated, but also able to reclassify just over 17% of women into a different risk group versus the clinical model.
The research (abstract P2-11-21) was presented at the San Antonio Breast Cancer Symposium on Dec. 8.
“This is the first breast cancer risk model based on a polygenic score, the 149-SNP PRS, that incorporates genetically determined ancestral composition and is validated for diverse ancestries,” the team reported.
The combined model substantially improved risk stratification over TC alone and may “lead to enhanced breast cancer risk reduction strategies, such as increased surveillance and use of preventive medications,” the researchers reported.
Breast cancer has a substantial genetic component that can “inform risk prediction and personalized preventive measures.” However, polygenic risk scores are largely derived from studies of women of European descent and tend to have poor performance in non-European ancestries.
Combined score substantially improved risk stratification over TC alone
The research team developed a polygenic risk score based on 149 SNPs for women of diverse backgrounds who did not have pathologic variants in breast cancer susceptibility genes, and included 56 ancestry-informative variants with 93 BC-associated variants. They combined the 149-SNP polygenic risk score with the TC risk model to create a combined risk score that was developed in a cohort of 145,786 women who were unaffected by breast cancer, following a fixed-stratified model to avoid double counting between confounded factors.
Of the women included in the cohort, 69.1% were of European descent, while 10.2% were Hispanic, 10.0% Black/African, 1.9% Asian, and 8.8% all other groups.
An independent cohort of 68,803 women of a similar ethnic distribution was then used to evaluate the calibration of the combined risk score against the TC risk model alone, and to examine the relative contributions of the 149-SNP PRS, family history, and other clinical factors.
The results showed that, overall, the combined risk score was well calibrated across ancestries and percentiles of risks, and the absolute lifetime risks were similar to those derived from the TC risk model alone. The only exception was Hispanic carriers of a protective Amerindian SNP who had a lower score on the combined risk score than the TC model.
Using an ANOVA model, the team found that family history contributed 48% to the lifetime risk of breast cancer, while the 149-SNP PRS contributed 35% and other factors 17%. Family history was weakly, but significantly correlated with the 149-SNP PRS.
Determining the impact of adding the 149-SNP PRS to the TC risk model on risk classification, the team showed that across all ancestries, 17.3% of women were reclassified by the combined risk score versus the TC model alone, with 10.8% having their lifetime risk increased to high risk and 29.1% having their risk decreased by the combined model to low risk.
The largest reclassifications were seen for women of European descent, while the smallest were for Black/African women.
Study may have ‘cracked the code’
“What’s exciting is that I think we kind-of ‘cracked the code’ to some extent of how to do this across diseases for all ancestries,” Thomas P. Slavin, MD, chief medical officer at Myriad Genetics, said in an interview. “The adaptation for breast cancer risk stratification and the new panel [is] for breast cancer across all ancestries, but what we developed is something that could be used across diabetes, or colon cancer, or anything.”
He explained that they realized that “for each one of these little hot spots” in the SNPs, “that make one person different from another, you really need to find out where in the world that originated from. So, if you have genetic ancestry on an individual, you can say this spot in the genome has more of an African ancestry to it, or a European ancestry, and then you can weight it appropriately by the population.”
Dr. Slavin said that standard PRSs that simply add up SNPs are “pretty good” and “add a lot” to risk stratification, “but to fine-tune it a little bit and make the best risk model, you really do need to bring in clinical and family history factors.”
Montserrat García-Closas, MD, DrPH, deputy director of the cancer epidemiology and genetics for the National Cancer Institute, said the study is of interest, but “does not give information on how ancestry was considered in the models used to derive the scores.” She also cautioned that the method used in the study to calibrate the model seems “to mean a comparison of scores, rather than comparing the observed and expected risk in prospective cohorts by ancestry groups. This would be a way to estimate bias in risk prediction by ancestry.”
Nevertheless, Dr. García-Closas said the degree of risk reclassification seen with the combined risk score is as expected and pointed to recent work by her and her colleagues in which they tested an integrated model incorporating classical risk factors and a 313-variant PRS to predict breast-cancer risk and achieved similar results.
Several study authors disclosed ties with Myriad Genetics, as well as AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Helix BioPharma, Konica Minolta, Ambry Genetics, Invitae, Stryker, GAIL, Phenogen Sciences, Novartis, Pfizer, CancerIQ, Tempus, 54gene, Color Genetics, Roche/Genentech, ImpediMed, Prelude Therapeutics, BD, Agendia, Targeted Medical Education, Cerebrotech Medical Systems, Integra LifeSciences, Puma Biotechnology, GeneDX/BioReference, Change Health Care, Research to Practice, Clinical Care Options, Physician Education Resource, and Daiichi Sankyo.
The headline for this article was updated on 1/6/22.
FROM SABCS 2021
Does atopic dermatitis pose an increased risk of acquiring COVID-19?
According to the best available evidence, patients with atopic dermatitis (AD) do not appear to face an increased risk of acquiring COVID-19 or becoming hospitalized because of the virus.
“This is an area that will continue to evolve, and further understanding will improve the health care advice that we provide to our patients,” Jacob P. Thyssen, MD, PhD, DmSci, said at the Revolutionizing Atopic Dermatitis virtual symposium. “The general recommendation for now is to continue systemic AD treatments during the pandemic, but the risk of acquiring COVID-19 is different for different drugs.”
According to Thyssen, professor of dermatology at the University of Copenhagen, early management guidance from the European Task Force on Atopic Dermatitis (ETFAD), the European Academy of Allergy and Clinical Immunology (EAACI), and the International Eczema Council (IEC) state that patients with AD who are on biologics or immunosuppressants should continue treatment if they are not infected with COVID-19. For example, the EIC statement says that the IEC “does not recommend temporary interruption of systemic AD treatments affecting the immune system in patients without COVID-19 infection or in those who have COVID-19 but are asymptomatic or have only mild symptoms.”
Guidelines from the EAACI recommend that patients with AD who become infected with COVID-19 withhold biologic treatment for a minimum of 2 weeks until they have recovered and/or have a negative SARS-CoV-2 test.
“However, if you have more severe respiratory disease, the advice to dermatologists is to consult with an infectious medicine specialist or a pulmonologist,” Dr. Thyssen said. “That’s out of our specialty realm. But in terms of AD, there’s no reason to stop treatment as long as the patient has mild symptoms or is asymptomatic. AD patients treated with immunosuppressive agents may have a higher risk of COVID-19 complications. Treatment with traditional immunosuppressant medications does increase the risk of infections. But what about COVID-19?”
Traditional systemic immunosuppressive therapies in AD with azathioprine, cyclosporine, and methotrexate suppress the immune system for 1-3 months, Dr. Thyssen continued. “We do know that vaccination response is reduced when using these agents,” he said. “The half-life of dupilumab [Dupixent] is 12-21 days. It takes about 13 weeks before dupilumab is completely out of the system, but it’s such a targeted therapy that it doesn’t lead to any broad immunosuppression.”
Meanwhile, the half-life of JAK inhibitors such as baricitinib (Olumiant) is about 13 hours. “It’s a broader immune suppressant because there will be off-target effects if you have a high dose, but it’s much more specific than the traditional immunosuppressants,” he said. “We now have JAK1 and JAK2 inhibitors in AD, which do not interfere with vaccine responses to the same degree as traditional immunosuppressants.”
To evaluate the risk for COVID-19 in patients with AD, researchers from the Center for Dermatology Research at the University of Manchester, United Kingdom, performed a cross-sectional study of 13,162 dermatology patients seen in the U.K. between June 2018 and Feb. 2021. Of the 13,162 patients, 624 (4.7%) had AD. They found that 4.8% of patients without a history of COVID-19 infection had AD, compared with 3.4% with a history of COVID-19. The risk for COVID-19 in patients with AD was similar to that of controls (adjusted odds ratio, 0.67).
Authors of a separate cross-sectional study published in May evaluated the health insurance medical records of 269,299 patients who were tested for SARS-CoV-2 across University of California Medical Centers. Of these, 3.6% had a positive test for SARS-CoV-2. Of 5,387 patients with AD, the infection rate was 2.9%, which was lower than in those without AD (3.7%; P = .0063). Hospitalization and mortality were not increased in patients with AD.
Another study, a case-control of more than 4.6 million HMO patients in Israel, found that the intake of systemic corticosteroids, older age, comorbid cardiovascular diseases, metabolic syndrome, and COPD were independent predictors of COVID-19–associated hospitalization. Mortality as a result of COVID-19 was independently predicted by metabolic syndrome and COPD but not by any AD-related variables.
“So, for our AD patients out there, there is no need to fear that they develop a COVID-19 infection or have a severe course, but we do have a few medications that would slightly increase the risk,” Dr. Thyssen said.
In another analysis, researchers evaluated Symphony Health–derived data from the COVID-19 Research Database to evaluate the risk for COVID-19 infection in adults with AD. The AD cohort included 39,417 patients, and the cohort without AD included 397,293 patients. Among AD patients, 8,180 were prescribed prednisone, 2,793 were prescribed dupilumab, 714 were prescribed methotrexate, and 512 were prescribed cyclosporine. The risk for COVID-19 was slightly increased in the AD cohort compared with the non-AD cohort (adjusted incidence rate ratio [IRR], 1.18; P < .0001).
“There can be various explanations for this,” Dr. Thyssen said. “I still think we should maintain that AD itself is not a risk factor for COVID-19, but some of the medications may slightly increase the risk.”
In other findings, the investigators observed that treatment with dupilumab versus no systemic medication decreased the risk for COVID-19 by 34% (adjusted IRR, 0.66; P < .0001), as did methotrexate by 18% (adjusted IRR 0.82; P = .32). However, compared with no systemic medication, the use of prednisone slightly increased the risk of COVID-19 (adjusted IRR, 1.13; P = .03), as did the use of cyclosporine (adjusted IRR, 1.20; P = .32) and azathioprine (adjusted IRR, 1.61; P = .16).
More recently, researchers evaluated the records of 1,237 patients with moderate-to-severe AD (aged 9-95 years) to assess the self-reported severity of COVID-19 symptoms among those who received dupilumab versus other treatments.
Of the 1,237 patients with AD, 632 were on dupilumab, 107 were on other systemic treatments, and 498 were on limited or no treatment. Patients treated with dupilumab were less likely to report moderate-to-severe COVID-19 symptoms compared with patients who were on other systemic treatments, or limited/no treatments.
Vaccines and AD
Dr. Thyssen pointed out that the risk-benefit ratio of currently approved COVID-19 vaccines is better than the risk for an infection with SARS-CoV-2. “AD is not a contraindication to vaccination,” he said. “COVID-19 vaccine does not cause AD worsening since the vaccination response is mainly Th1 skewed.” He added that systemic immunosuppressants and JAK inhibitors used to treat AD may attenuate the vaccination response, but no attenuation is expected with dupilumab. “The half-life of JAK inhibitors is so short that vaccination followed by 1 week of pause treatment is a good strategy for patients.”
Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Asian, Arena, Almirall, AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.
A version of this article first appeared on Medscape.com.
According to the best available evidence, patients with atopic dermatitis (AD) do not appear to face an increased risk of acquiring COVID-19 or becoming hospitalized because of the virus.
“This is an area that will continue to evolve, and further understanding will improve the health care advice that we provide to our patients,” Jacob P. Thyssen, MD, PhD, DmSci, said at the Revolutionizing Atopic Dermatitis virtual symposium. “The general recommendation for now is to continue systemic AD treatments during the pandemic, but the risk of acquiring COVID-19 is different for different drugs.”
According to Thyssen, professor of dermatology at the University of Copenhagen, early management guidance from the European Task Force on Atopic Dermatitis (ETFAD), the European Academy of Allergy and Clinical Immunology (EAACI), and the International Eczema Council (IEC) state that patients with AD who are on biologics or immunosuppressants should continue treatment if they are not infected with COVID-19. For example, the EIC statement says that the IEC “does not recommend temporary interruption of systemic AD treatments affecting the immune system in patients without COVID-19 infection or in those who have COVID-19 but are asymptomatic or have only mild symptoms.”
Guidelines from the EAACI recommend that patients with AD who become infected with COVID-19 withhold biologic treatment for a minimum of 2 weeks until they have recovered and/or have a negative SARS-CoV-2 test.
“However, if you have more severe respiratory disease, the advice to dermatologists is to consult with an infectious medicine specialist or a pulmonologist,” Dr. Thyssen said. “That’s out of our specialty realm. But in terms of AD, there’s no reason to stop treatment as long as the patient has mild symptoms or is asymptomatic. AD patients treated with immunosuppressive agents may have a higher risk of COVID-19 complications. Treatment with traditional immunosuppressant medications does increase the risk of infections. But what about COVID-19?”
Traditional systemic immunosuppressive therapies in AD with azathioprine, cyclosporine, and methotrexate suppress the immune system for 1-3 months, Dr. Thyssen continued. “We do know that vaccination response is reduced when using these agents,” he said. “The half-life of dupilumab [Dupixent] is 12-21 days. It takes about 13 weeks before dupilumab is completely out of the system, but it’s such a targeted therapy that it doesn’t lead to any broad immunosuppression.”
Meanwhile, the half-life of JAK inhibitors such as baricitinib (Olumiant) is about 13 hours. “It’s a broader immune suppressant because there will be off-target effects if you have a high dose, but it’s much more specific than the traditional immunosuppressants,” he said. “We now have JAK1 and JAK2 inhibitors in AD, which do not interfere with vaccine responses to the same degree as traditional immunosuppressants.”
To evaluate the risk for COVID-19 in patients with AD, researchers from the Center for Dermatology Research at the University of Manchester, United Kingdom, performed a cross-sectional study of 13,162 dermatology patients seen in the U.K. between June 2018 and Feb. 2021. Of the 13,162 patients, 624 (4.7%) had AD. They found that 4.8% of patients without a history of COVID-19 infection had AD, compared with 3.4% with a history of COVID-19. The risk for COVID-19 in patients with AD was similar to that of controls (adjusted odds ratio, 0.67).
Authors of a separate cross-sectional study published in May evaluated the health insurance medical records of 269,299 patients who were tested for SARS-CoV-2 across University of California Medical Centers. Of these, 3.6% had a positive test for SARS-CoV-2. Of 5,387 patients with AD, the infection rate was 2.9%, which was lower than in those without AD (3.7%; P = .0063). Hospitalization and mortality were not increased in patients with AD.
Another study, a case-control of more than 4.6 million HMO patients in Israel, found that the intake of systemic corticosteroids, older age, comorbid cardiovascular diseases, metabolic syndrome, and COPD were independent predictors of COVID-19–associated hospitalization. Mortality as a result of COVID-19 was independently predicted by metabolic syndrome and COPD but not by any AD-related variables.
“So, for our AD patients out there, there is no need to fear that they develop a COVID-19 infection or have a severe course, but we do have a few medications that would slightly increase the risk,” Dr. Thyssen said.
In another analysis, researchers evaluated Symphony Health–derived data from the COVID-19 Research Database to evaluate the risk for COVID-19 infection in adults with AD. The AD cohort included 39,417 patients, and the cohort without AD included 397,293 patients. Among AD patients, 8,180 were prescribed prednisone, 2,793 were prescribed dupilumab, 714 were prescribed methotrexate, and 512 were prescribed cyclosporine. The risk for COVID-19 was slightly increased in the AD cohort compared with the non-AD cohort (adjusted incidence rate ratio [IRR], 1.18; P < .0001).
“There can be various explanations for this,” Dr. Thyssen said. “I still think we should maintain that AD itself is not a risk factor for COVID-19, but some of the medications may slightly increase the risk.”
In other findings, the investigators observed that treatment with dupilumab versus no systemic medication decreased the risk for COVID-19 by 34% (adjusted IRR, 0.66; P < .0001), as did methotrexate by 18% (adjusted IRR 0.82; P = .32). However, compared with no systemic medication, the use of prednisone slightly increased the risk of COVID-19 (adjusted IRR, 1.13; P = .03), as did the use of cyclosporine (adjusted IRR, 1.20; P = .32) and azathioprine (adjusted IRR, 1.61; P = .16).
More recently, researchers evaluated the records of 1,237 patients with moderate-to-severe AD (aged 9-95 years) to assess the self-reported severity of COVID-19 symptoms among those who received dupilumab versus other treatments.
Of the 1,237 patients with AD, 632 were on dupilumab, 107 were on other systemic treatments, and 498 were on limited or no treatment. Patients treated with dupilumab were less likely to report moderate-to-severe COVID-19 symptoms compared with patients who were on other systemic treatments, or limited/no treatments.
Vaccines and AD
Dr. Thyssen pointed out that the risk-benefit ratio of currently approved COVID-19 vaccines is better than the risk for an infection with SARS-CoV-2. “AD is not a contraindication to vaccination,” he said. “COVID-19 vaccine does not cause AD worsening since the vaccination response is mainly Th1 skewed.” He added that systemic immunosuppressants and JAK inhibitors used to treat AD may attenuate the vaccination response, but no attenuation is expected with dupilumab. “The half-life of JAK inhibitors is so short that vaccination followed by 1 week of pause treatment is a good strategy for patients.”
Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Asian, Arena, Almirall, AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.
A version of this article first appeared on Medscape.com.
According to the best available evidence, patients with atopic dermatitis (AD) do not appear to face an increased risk of acquiring COVID-19 or becoming hospitalized because of the virus.
“This is an area that will continue to evolve, and further understanding will improve the health care advice that we provide to our patients,” Jacob P. Thyssen, MD, PhD, DmSci, said at the Revolutionizing Atopic Dermatitis virtual symposium. “The general recommendation for now is to continue systemic AD treatments during the pandemic, but the risk of acquiring COVID-19 is different for different drugs.”
According to Thyssen, professor of dermatology at the University of Copenhagen, early management guidance from the European Task Force on Atopic Dermatitis (ETFAD), the European Academy of Allergy and Clinical Immunology (EAACI), and the International Eczema Council (IEC) state that patients with AD who are on biologics or immunosuppressants should continue treatment if they are not infected with COVID-19. For example, the EIC statement says that the IEC “does not recommend temporary interruption of systemic AD treatments affecting the immune system in patients without COVID-19 infection or in those who have COVID-19 but are asymptomatic or have only mild symptoms.”
Guidelines from the EAACI recommend that patients with AD who become infected with COVID-19 withhold biologic treatment for a minimum of 2 weeks until they have recovered and/or have a negative SARS-CoV-2 test.
“However, if you have more severe respiratory disease, the advice to dermatologists is to consult with an infectious medicine specialist or a pulmonologist,” Dr. Thyssen said. “That’s out of our specialty realm. But in terms of AD, there’s no reason to stop treatment as long as the patient has mild symptoms or is asymptomatic. AD patients treated with immunosuppressive agents may have a higher risk of COVID-19 complications. Treatment with traditional immunosuppressant medications does increase the risk of infections. But what about COVID-19?”
Traditional systemic immunosuppressive therapies in AD with azathioprine, cyclosporine, and methotrexate suppress the immune system for 1-3 months, Dr. Thyssen continued. “We do know that vaccination response is reduced when using these agents,” he said. “The half-life of dupilumab [Dupixent] is 12-21 days. It takes about 13 weeks before dupilumab is completely out of the system, but it’s such a targeted therapy that it doesn’t lead to any broad immunosuppression.”
Meanwhile, the half-life of JAK inhibitors such as baricitinib (Olumiant) is about 13 hours. “It’s a broader immune suppressant because there will be off-target effects if you have a high dose, but it’s much more specific than the traditional immunosuppressants,” he said. “We now have JAK1 and JAK2 inhibitors in AD, which do not interfere with vaccine responses to the same degree as traditional immunosuppressants.”
To evaluate the risk for COVID-19 in patients with AD, researchers from the Center for Dermatology Research at the University of Manchester, United Kingdom, performed a cross-sectional study of 13,162 dermatology patients seen in the U.K. between June 2018 and Feb. 2021. Of the 13,162 patients, 624 (4.7%) had AD. They found that 4.8% of patients without a history of COVID-19 infection had AD, compared with 3.4% with a history of COVID-19. The risk for COVID-19 in patients with AD was similar to that of controls (adjusted odds ratio, 0.67).
Authors of a separate cross-sectional study published in May evaluated the health insurance medical records of 269,299 patients who were tested for SARS-CoV-2 across University of California Medical Centers. Of these, 3.6% had a positive test for SARS-CoV-2. Of 5,387 patients with AD, the infection rate was 2.9%, which was lower than in those without AD (3.7%; P = .0063). Hospitalization and mortality were not increased in patients with AD.
Another study, a case-control of more than 4.6 million HMO patients in Israel, found that the intake of systemic corticosteroids, older age, comorbid cardiovascular diseases, metabolic syndrome, and COPD were independent predictors of COVID-19–associated hospitalization. Mortality as a result of COVID-19 was independently predicted by metabolic syndrome and COPD but not by any AD-related variables.
“So, for our AD patients out there, there is no need to fear that they develop a COVID-19 infection or have a severe course, but we do have a few medications that would slightly increase the risk,” Dr. Thyssen said.
In another analysis, researchers evaluated Symphony Health–derived data from the COVID-19 Research Database to evaluate the risk for COVID-19 infection in adults with AD. The AD cohort included 39,417 patients, and the cohort without AD included 397,293 patients. Among AD patients, 8,180 were prescribed prednisone, 2,793 were prescribed dupilumab, 714 were prescribed methotrexate, and 512 were prescribed cyclosporine. The risk for COVID-19 was slightly increased in the AD cohort compared with the non-AD cohort (adjusted incidence rate ratio [IRR], 1.18; P < .0001).
“There can be various explanations for this,” Dr. Thyssen said. “I still think we should maintain that AD itself is not a risk factor for COVID-19, but some of the medications may slightly increase the risk.”
In other findings, the investigators observed that treatment with dupilumab versus no systemic medication decreased the risk for COVID-19 by 34% (adjusted IRR, 0.66; P < .0001), as did methotrexate by 18% (adjusted IRR 0.82; P = .32). However, compared with no systemic medication, the use of prednisone slightly increased the risk of COVID-19 (adjusted IRR, 1.13; P = .03), as did the use of cyclosporine (adjusted IRR, 1.20; P = .32) and azathioprine (adjusted IRR, 1.61; P = .16).
More recently, researchers evaluated the records of 1,237 patients with moderate-to-severe AD (aged 9-95 years) to assess the self-reported severity of COVID-19 symptoms among those who received dupilumab versus other treatments.
Of the 1,237 patients with AD, 632 were on dupilumab, 107 were on other systemic treatments, and 498 were on limited or no treatment. Patients treated with dupilumab were less likely to report moderate-to-severe COVID-19 symptoms compared with patients who were on other systemic treatments, or limited/no treatments.
Vaccines and AD
Dr. Thyssen pointed out that the risk-benefit ratio of currently approved COVID-19 vaccines is better than the risk for an infection with SARS-CoV-2. “AD is not a contraindication to vaccination,” he said. “COVID-19 vaccine does not cause AD worsening since the vaccination response is mainly Th1 skewed.” He added that systemic immunosuppressants and JAK inhibitors used to treat AD may attenuate the vaccination response, but no attenuation is expected with dupilumab. “The half-life of JAK inhibitors is so short that vaccination followed by 1 week of pause treatment is a good strategy for patients.”
Dr. Thyssen disclosed that he is a speaker, advisory board member, and/or investigator for Asian, Arena, Almirall, AbbVie, Eli Lilly, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme.
A version of this article first appeared on Medscape.com.
FROM REVOLUTIONIZING AD 2021