Clinician Reviews

As obstacles to hepatitis C treatment uptake were removed, rates of hepatitis-related liver disease in marginalized groups plummeted, according to a new study in Baltimore, published in Annals of Internal Medicine.

A community-based cohort study that follows current and former people who inject drugs (PWID) with hepatitis C documented drastic reductions in liver disease and death as effective oral antivirals became more readily accessible there between 2015 and 2019.

The researchers concluded that hepatitis C elimination targets are achievable. But, they warned, uptake is uneven, and more needs to be done to facilitate treatment.

“[The study] gives us a real-world perspective on what’s happening on the ground, in terms of people getting treated,” said first author Javier Cepeda, PhD, MPH, an assistant professor at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. “Changing policy, reducing barriers, [and] getting them access to treatment really does have this really important public health benefit.”

“It’s compelling to see these improved outcomes amongst a cohort of people who inject drugs with baseline hep C,” said Maria Corcorran, MD, MPH. Dr. Corcorran, an acting assistant professor for the department of medicine at the University of Washington, was not involved with the study. “It’s just further evidence that we need to really be linking people to care and getting people treated and cured.”

The World Health Organization has called for the disease’s global elimination by 2030. Cure rates top 95%. But, there are so many new cases and so many barriers to detection and treatment that how to develop and roll out a public health response is the most important question in the field, wrote study co-author David L. Thomas, MD, MPH, in a review article in The New England Journal of Medicine.

“Folks who inject drugs ... do well on hep C treatment and have similar rates of sustained virologic response or cure,” said Dr. Corcorran, who runs a low-barrier clinic for people experiencing homelessness.

But, she added, “there are barriers that are still put up to treatment in terms of who can treat and what insurance is going to cover.”
 

A look at a vulnerable population

The authors studied adults enrolled in ALIVE (AIDS Linked to the Intravenous Experience), a cohort study that has recruited current and former PWID in the Baltimore area since 1988.

Participants visit the clinic twice a year for health-related interviews and blood testing, including HIV serology, hepatitis C virus (HCV) antibody and RNA testing, and liver function tests. They are counseled about HCV testing and treatment but do not receive treatment through the study.

Beginning in 2006, researchers added liver stiffness measures (LSMs), a noninvasive measure conducted with transient elastography.

From 2006 to 2019, the authors followed 1,323 ALIVE participants with chronic HCV infection. The primary outcome was LSMs.
 

Less liver disease, fewer deaths

At baseline, participants’ median age was 49 years; 82% of participants were Black individuals, 71% percent were male, and two-thirds were HIV-negative.

Three percent reported receiving hepatitis C treatment in 2014, which increased to 39% in 2019.

Among 10,350 LSMs, 15% showed cirrhosis at baseline in 2006. In 2015, that rose to 19%, but by 2019, it had fallen to 8%.

By definition, 100% had detectable HCV RNA at baseline. In 2015, 91% still did. By 2019, that rate had fallen to 48%.

Undetectable HCV RNA correlated with lower log LSM in adjusted models (P < .001). It also correlated strongly with lower odds of liver cirrhosis, with an adjusted odds ratio of 0.28 (95% confidence interval, 0.17-0.45; P < .001). In addition, it correlated with lower risk for all-cause mortality, with an adjusted hazard ratio of 0.54 (95% CI, 0.38-0.77; P < .001).

Limitations include the fact that, although transient elastography is considered the most valid way to detect cirrhosis in people with hepatitis C, liver stiffness has not been validated as a measure of fibrosis among people with a sustained virologic response.

In addition, ALIVE participants are older and more likely to be African American individuals, compared with the general population of PWID in Baltimore, wrote co-author Shruti H. Mehta, PhD, a professor of epidemiology at Johns Hopkins University, Baltimore, in an email exchange with this news organization. That could affect generalizability.
 

Treatment is crucial

The first direct-acting antiviral (DAA) for hepatitis C was approved in 2011, and an oral fixed-dose combination antiviral was approved in 2014, ushering in treatments with cure rates far exceeding those with interferon-based therapy.

But until recently, Medicaid patients in Maryland seeking DAA therapy for hepatitis C required prior authorization, with initial restrictions related to disease stage, substance use, and provider type, according to Dr. Mehta.

Gradually, those restrictions were lifted, Dr. Mehta added, and all were eliminated by 2019.

Dr. Cepeda urges clinicians to treat patients infected with hepatitis C immediately.

“There are really important implications on both reducing liver disease progression and all-cause mortality,” he said.

“Hep C is just one part of a whole constellation of health care delivery [and] of treating all of the other potential problems that might need to be addressed – especially with people who inject drugs,” Dr. Cepeda added. “Getting them into care is really, really important.”

The study was funded by the National Institutes of Health. Dr. Cepeda and Dr. Corcorran report no relevant financial relationships. Dr. Mehta reports receiving payments or honoraria and travel support from Gilead Sciences, the makers of the oral hepatitis C medication ledipasvir/sofosbuvir (Harvoni), as well as equipment, materials, drugs, medical writing, gifts, or other services from Abbott, which sells hepatitis C diagnostics. Dr. Thomas reports ties to Excision Bio and to Merck DSMB.

A version of this article first appeared on Medscape.com.

As obstacles to hepatitis C treatment uptake were removed, rates of hepatitis-related liver disease in marginalized groups plummeted, according to a new study in Baltimore, published in Annals of Internal Medicine.

A community-based cohort study that follows current and former people who inject drugs (PWID) with hepatitis C documented drastic reductions in liver disease and death as effective oral antivirals became more readily accessible there between 2015 and 2019.

The researchers concluded that hepatitis C elimination targets are achievable. But, they warned, uptake is uneven, and more needs to be done to facilitate treatment.

“[The study] gives us a real-world perspective on what’s happening on the ground, in terms of people getting treated,” said first author Javier Cepeda, PhD, MPH, an assistant professor at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. “Changing policy, reducing barriers, [and] getting them access to treatment really does have this really important public health benefit.”

“It’s compelling to see these improved outcomes amongst a cohort of people who inject drugs with baseline hep C,” said Maria Corcorran, MD, MPH. Dr. Corcorran, an acting assistant professor for the department of medicine at the University of Washington, was not involved with the study. “It’s just further evidence that we need to really be linking people to care and getting people treated and cured.”

The World Health Organization has called for the disease’s global elimination by 2030. Cure rates top 95%. But, there are so many new cases and so many barriers to detection and treatment that how to develop and roll out a public health response is the most important question in the field, wrote study co-author David L. Thomas, MD, MPH, in a review article in The New England Journal of Medicine.

“Folks who inject drugs ... do well on hep C treatment and have similar rates of sustained virologic response or cure,” said Dr. Corcorran, who runs a low-barrier clinic for people experiencing homelessness.

But, she added, “there are barriers that are still put up to treatment in terms of who can treat and what insurance is going to cover.”
 

A look at a vulnerable population

The authors studied adults enrolled in ALIVE (AIDS Linked to the Intravenous Experience), a cohort study that has recruited current and former PWID in the Baltimore area since 1988.

Participants visit the clinic twice a year for health-related interviews and blood testing, including HIV serology, hepatitis C virus (HCV) antibody and RNA testing, and liver function tests. They are counseled about HCV testing and treatment but do not receive treatment through the study.

Beginning in 2006, researchers added liver stiffness measures (LSMs), a noninvasive measure conducted with transient elastography.

From 2006 to 2019, the authors followed 1,323 ALIVE participants with chronic HCV infection. The primary outcome was LSMs.
 

Less liver disease, fewer deaths

At baseline, participants’ median age was 49 years; 82% of participants were Black individuals, 71% percent were male, and two-thirds were HIV-negative.

Three percent reported receiving hepatitis C treatment in 2014, which increased to 39% in 2019.

Among 10,350 LSMs, 15% showed cirrhosis at baseline in 2006. In 2015, that rose to 19%, but by 2019, it had fallen to 8%.

By definition, 100% had detectable HCV RNA at baseline. In 2015, 91% still did. By 2019, that rate had fallen to 48%.

Undetectable HCV RNA correlated with lower log LSM in adjusted models (P < .001). It also correlated strongly with lower odds of liver cirrhosis, with an adjusted odds ratio of 0.28 (95% confidence interval, 0.17-0.45; P < .001). In addition, it correlated with lower risk for all-cause mortality, with an adjusted hazard ratio of 0.54 (95% CI, 0.38-0.77; P < .001).

Limitations include the fact that, although transient elastography is considered the most valid way to detect cirrhosis in people with hepatitis C, liver stiffness has not been validated as a measure of fibrosis among people with a sustained virologic response.

In addition, ALIVE participants are older and more likely to be African American individuals, compared with the general population of PWID in Baltimore, wrote co-author Shruti H. Mehta, PhD, a professor of epidemiology at Johns Hopkins University, Baltimore, in an email exchange with this news organization. That could affect generalizability.
 

Treatment is crucial

The first direct-acting antiviral (DAA) for hepatitis C was approved in 2011, and an oral fixed-dose combination antiviral was approved in 2014, ushering in treatments with cure rates far exceeding those with interferon-based therapy.

But until recently, Medicaid patients in Maryland seeking DAA therapy for hepatitis C required prior authorization, with initial restrictions related to disease stage, substance use, and provider type, according to Dr. Mehta.

Gradually, those restrictions were lifted, Dr. Mehta added, and all were eliminated by 2019.

Dr. Cepeda urges clinicians to treat patients infected with hepatitis C immediately.

“There are really important implications on both reducing liver disease progression and all-cause mortality,” he said.

“Hep C is just one part of a whole constellation of health care delivery [and] of treating all of the other potential problems that might need to be addressed – especially with people who inject drugs,” Dr. Cepeda added. “Getting them into care is really, really important.”

The study was funded by the National Institutes of Health. Dr. Cepeda and Dr. Corcorran report no relevant financial relationships. Dr. Mehta reports receiving payments or honoraria and travel support from Gilead Sciences, the makers of the oral hepatitis C medication ledipasvir/sofosbuvir (Harvoni), as well as equipment, materials, drugs, medical writing, gifts, or other services from Abbott, which sells hepatitis C diagnostics. Dr. Thomas reports ties to Excision Bio and to Merck DSMB.

A version of this article first appeared on Medscape.com.

As obstacles to hepatitis C treatment uptake were removed, rates of hepatitis-related liver disease in marginalized groups plummeted, according to a new study in Baltimore, published in Annals of Internal Medicine.

A community-based cohort study that follows current and former people who inject drugs (PWID) with hepatitis C documented drastic reductions in liver disease and death as effective oral antivirals became more readily accessible there between 2015 and 2019.

The researchers concluded that hepatitis C elimination targets are achievable. But, they warned, uptake is uneven, and more needs to be done to facilitate treatment.

“[The study] gives us a real-world perspective on what’s happening on the ground, in terms of people getting treated,” said first author Javier Cepeda, PhD, MPH, an assistant professor at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. “Changing policy, reducing barriers, [and] getting them access to treatment really does have this really important public health benefit.”

“It’s compelling to see these improved outcomes amongst a cohort of people who inject drugs with baseline hep C,” said Maria Corcorran, MD, MPH. Dr. Corcorran, an acting assistant professor for the department of medicine at the University of Washington, was not involved with the study. “It’s just further evidence that we need to really be linking people to care and getting people treated and cured.”

The World Health Organization has called for the disease’s global elimination by 2030. Cure rates top 95%. But, there are so many new cases and so many barriers to detection and treatment that how to develop and roll out a public health response is the most important question in the field, wrote study co-author David L. Thomas, MD, MPH, in a review article in The New England Journal of Medicine.

“Folks who inject drugs ... do well on hep C treatment and have similar rates of sustained virologic response or cure,” said Dr. Corcorran, who runs a low-barrier clinic for people experiencing homelessness.

But, she added, “there are barriers that are still put up to treatment in terms of who can treat and what insurance is going to cover.”
 

A look at a vulnerable population

The authors studied adults enrolled in ALIVE (AIDS Linked to the Intravenous Experience), a cohort study that has recruited current and former PWID in the Baltimore area since 1988.

Participants visit the clinic twice a year for health-related interviews and blood testing, including HIV serology, hepatitis C virus (HCV) antibody and RNA testing, and liver function tests. They are counseled about HCV testing and treatment but do not receive treatment through the study.

Beginning in 2006, researchers added liver stiffness measures (LSMs), a noninvasive measure conducted with transient elastography.

From 2006 to 2019, the authors followed 1,323 ALIVE participants with chronic HCV infection. The primary outcome was LSMs.
 

Less liver disease, fewer deaths

At baseline, participants’ median age was 49 years; 82% of participants were Black individuals, 71% percent were male, and two-thirds were HIV-negative.

Three percent reported receiving hepatitis C treatment in 2014, which increased to 39% in 2019.

Among 10,350 LSMs, 15% showed cirrhosis at baseline in 2006. In 2015, that rose to 19%, but by 2019, it had fallen to 8%.

By definition, 100% had detectable HCV RNA at baseline. In 2015, 91% still did. By 2019, that rate had fallen to 48%.

Undetectable HCV RNA correlated with lower log LSM in adjusted models (P < .001). It also correlated strongly with lower odds of liver cirrhosis, with an adjusted odds ratio of 0.28 (95% confidence interval, 0.17-0.45; P < .001). In addition, it correlated with lower risk for all-cause mortality, with an adjusted hazard ratio of 0.54 (95% CI, 0.38-0.77; P < .001).

Limitations include the fact that, although transient elastography is considered the most valid way to detect cirrhosis in people with hepatitis C, liver stiffness has not been validated as a measure of fibrosis among people with a sustained virologic response.

In addition, ALIVE participants are older and more likely to be African American individuals, compared with the general population of PWID in Baltimore, wrote co-author Shruti H. Mehta, PhD, a professor of epidemiology at Johns Hopkins University, Baltimore, in an email exchange with this news organization. That could affect generalizability.
 

Treatment is crucial

The first direct-acting antiviral (DAA) for hepatitis C was approved in 2011, and an oral fixed-dose combination antiviral was approved in 2014, ushering in treatments with cure rates far exceeding those with interferon-based therapy.

But until recently, Medicaid patients in Maryland seeking DAA therapy for hepatitis C required prior authorization, with initial restrictions related to disease stage, substance use, and provider type, according to Dr. Mehta.

Gradually, those restrictions were lifted, Dr. Mehta added, and all were eliminated by 2019.

Dr. Cepeda urges clinicians to treat patients infected with hepatitis C immediately.

“There are really important implications on both reducing liver disease progression and all-cause mortality,” he said.

“Hep C is just one part of a whole constellation of health care delivery [and] of treating all of the other potential problems that might need to be addressed – especially with people who inject drugs,” Dr. Cepeda added. “Getting them into care is really, really important.”

The study was funded by the National Institutes of Health. Dr. Cepeda and Dr. Corcorran report no relevant financial relationships. Dr. Mehta reports receiving payments or honoraria and travel support from Gilead Sciences, the makers of the oral hepatitis C medication ledipasvir/sofosbuvir (Harvoni), as well as equipment, materials, drugs, medical writing, gifts, or other services from Abbott, which sells hepatitis C diagnostics. Dr. Thomas reports ties to Excision Bio and to Merck DSMB.

A version of this article first appeared on Medscape.com.

Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate. Two published studies have drawn attention to long COVID-19 signs and symptoms in these patients.

Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).

The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
 

Definitions are changing

In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”

Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.

In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).

These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”

The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.

In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.

The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.

The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).

In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.

The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.

“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”

“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”

The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
 

Danish parent survey

The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.

Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.

Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.

Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
 

More information needed

Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.

Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”

Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.

She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”

Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”

There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.

This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate. Two published studies have drawn attention to long COVID-19 signs and symptoms in these patients.

Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).

The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
 

Definitions are changing

In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”

Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.

In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).

These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”

The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.

In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.

The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.

The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).

In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.

The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.

“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”

“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”

The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
 

Danish parent survey

The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.

Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.

Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.

Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
 

More information needed

Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.

Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”

Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.

She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”

Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”

There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.

This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate. Two published studies have drawn attention to long COVID-19 signs and symptoms in these patients.

Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).

The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
 

Definitions are changing

In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”

Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.

In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).

These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”

The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.

In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.

The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.

The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).

In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.

The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.

“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”

“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”

The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
 

Danish parent survey

The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.

Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.

Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.

Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
 

More information needed

Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.

Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”

Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.

She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”

Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”

There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.

This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.

INDIANAPOLIS – Infants and preschoolers with atopic dermatitis (AD) experience a substantial disease burden across several domains, including atopic comorbidities, pruritus, sleep loss, hospitalizations, frequent prolonged flares, and school attendance. Those are key findings from a large international web-based survey that was presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

“Improved knowledge of the AD-related burden may help reinforce the medical need in the pediatric population and contribute to better and earlier adequate management of the disease,” authors led by Stephan Weidinger , MD, PhD, vice head of the department of dermatology at University Hospital Schleswig-Holstein, Kiel, Germany, wrote in the abstract.

For the study, Dr. Weidinger and colleagues evaluated 1,486 infants and preschoolers with AD aged 6 months to under 6 years, who participated in the Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE), an international, cross-sectional, web-based survey of children and adolescents. The study population resided in 18 countries from five regions of the world, including North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Parents or guardians answered all questions for infants/preschoolers younger than 4 years of age, while preschoolers aged 4 to younger than 6 years were asked to answer questions related to the impact of AD on their health-related quality of life.

AD severity was assessed using Patient Global Assessment (PtGA), where parents or guardians described their child’s eczema severity over the last week as mild, moderate, or severe. The researchers stratified outcomes by geographic region and AD severity, which included the following atopic comorbidities: worst itch, worst skin pain, and overall sleep disturbance in the past 24 hours as measured by the 0-10 numeric rating scale, where higher scores indicate worse severity; eczema-related hospitalization in the past 12 months; and frequency and average duration of flares over the past month.

The mean age of the study participants was 3 years and 61.6% had mild disease. The most common atopic comorbidities were hay fever, asthma, and seasonal allergies, and the incidence of atopic comorbidities increased with increasing AD severity. One or more atopic comorbidities was reported in 88.3% of patients with mild AD, compared with 92.1% of those with moderate disease and 95.8% of those with severe disease. In addition, infants and preschoolers with moderate or severe AD had worse itch, skin pain, and sleep disturbances over the past 24 hours, compared with those who had mild AD.

More than half of infants and preschoolers with severe AD (54.1%) were reported to have been hospitalized in the past 12 months (this ranged from 30.2% to 71.3% across regions), as did 35% of patients with moderate AD and 32.1% of those with mild AD. In addition, 50.6% of infants and preschoolers with severe AD had more than two flares in the past month, compared with 18.1% of those with moderate AD and 6.3% of those with mild disease.

In other findings, 50.7% of infants and preschoolers with severe AD had flares than lasted an average of 2 or more weeks, compared with 20.8% of those with moderate disease and 10% of those with mild disease. Also, 78.3% of preschoolers aged 4 to less than 6 years had missed one or more days of school in the previous 4 weeks: a mean of 5.1 days among those with mild AD, a mean of 7.3 days among those with moderate AD, and a mean of 12.1 days among those with severe disease.

Raj J. Chovatiya MD, PhD, of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that infants and preschoolers remain an understudied group despite the high prevalence of AD in this age range. “The results of this study demonstrate a substantial burden of disease in this population, particularly among those with more severe disease,” said Dr. Chovatiya, who also directs the university’s Center for Eczema and Itch. “This includes longer and more frequent AD flares as well as high rates of inpatient hospitalization. These findings suggest that additional research is needed to better characterize disease burden and optimize outcomes for young children with AD.”

The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Weidinger and other coauthors reported having received institutional research grants and consulting fees from many pharmaceutical companies that manufacture drugs used for the treatment of psoriasis and eczema.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly, EPI Health, Incyte, L’Oréal, the National Eczema Association, Pfizer, Regeneron, Sanofi, and UCB.

INDIANAPOLIS – Infants and preschoolers with atopic dermatitis (AD) experience a substantial disease burden across several domains, including atopic comorbidities, pruritus, sleep loss, hospitalizations, frequent prolonged flares, and school attendance. Those are key findings from a large international web-based survey that was presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

“Improved knowledge of the AD-related burden may help reinforce the medical need in the pediatric population and contribute to better and earlier adequate management of the disease,” authors led by Stephan Weidinger , MD, PhD, vice head of the department of dermatology at University Hospital Schleswig-Holstein, Kiel, Germany, wrote in the abstract.

For the study, Dr. Weidinger and colleagues evaluated 1,486 infants and preschoolers with AD aged 6 months to under 6 years, who participated in the Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE), an international, cross-sectional, web-based survey of children and adolescents. The study population resided in 18 countries from five regions of the world, including North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Parents or guardians answered all questions for infants/preschoolers younger than 4 years of age, while preschoolers aged 4 to younger than 6 years were asked to answer questions related to the impact of AD on their health-related quality of life.

AD severity was assessed using Patient Global Assessment (PtGA), where parents or guardians described their child’s eczema severity over the last week as mild, moderate, or severe. The researchers stratified outcomes by geographic region and AD severity, which included the following atopic comorbidities: worst itch, worst skin pain, and overall sleep disturbance in the past 24 hours as measured by the 0-10 numeric rating scale, where higher scores indicate worse severity; eczema-related hospitalization in the past 12 months; and frequency and average duration of flares over the past month.

The mean age of the study participants was 3 years and 61.6% had mild disease. The most common atopic comorbidities were hay fever, asthma, and seasonal allergies, and the incidence of atopic comorbidities increased with increasing AD severity. One or more atopic comorbidities was reported in 88.3% of patients with mild AD, compared with 92.1% of those with moderate disease and 95.8% of those with severe disease. In addition, infants and preschoolers with moderate or severe AD had worse itch, skin pain, and sleep disturbances over the past 24 hours, compared with those who had mild AD.

More than half of infants and preschoolers with severe AD (54.1%) were reported to have been hospitalized in the past 12 months (this ranged from 30.2% to 71.3% across regions), as did 35% of patients with moderate AD and 32.1% of those with mild AD. In addition, 50.6% of infants and preschoolers with severe AD had more than two flares in the past month, compared with 18.1% of those with moderate AD and 6.3% of those with mild disease.

In other findings, 50.7% of infants and preschoolers with severe AD had flares than lasted an average of 2 or more weeks, compared with 20.8% of those with moderate disease and 10% of those with mild disease. Also, 78.3% of preschoolers aged 4 to less than 6 years had missed one or more days of school in the previous 4 weeks: a mean of 5.1 days among those with mild AD, a mean of 7.3 days among those with moderate AD, and a mean of 12.1 days among those with severe disease.

Raj J. Chovatiya MD, PhD, of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that infants and preschoolers remain an understudied group despite the high prevalence of AD in this age range. “The results of this study demonstrate a substantial burden of disease in this population, particularly among those with more severe disease,” said Dr. Chovatiya, who also directs the university’s Center for Eczema and Itch. “This includes longer and more frequent AD flares as well as high rates of inpatient hospitalization. These findings suggest that additional research is needed to better characterize disease burden and optimize outcomes for young children with AD.”

The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Weidinger and other coauthors reported having received institutional research grants and consulting fees from many pharmaceutical companies that manufacture drugs used for the treatment of psoriasis and eczema.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly, EPI Health, Incyte, L’Oréal, the National Eczema Association, Pfizer, Regeneron, Sanofi, and UCB.

INDIANAPOLIS – Infants and preschoolers with atopic dermatitis (AD) experience a substantial disease burden across several domains, including atopic comorbidities, pruritus, sleep loss, hospitalizations, frequent prolonged flares, and school attendance. Those are key findings from a large international web-based survey that was presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

“Improved knowledge of the AD-related burden may help reinforce the medical need in the pediatric population and contribute to better and earlier adequate management of the disease,” authors led by Stephan Weidinger , MD, PhD, vice head of the department of dermatology at University Hospital Schleswig-Holstein, Kiel, Germany, wrote in the abstract.

For the study, Dr. Weidinger and colleagues evaluated 1,486 infants and preschoolers with AD aged 6 months to under 6 years, who participated in the Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE), an international, cross-sectional, web-based survey of children and adolescents. The study population resided in 18 countries from five regions of the world, including North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Parents or guardians answered all questions for infants/preschoolers younger than 4 years of age, while preschoolers aged 4 to younger than 6 years were asked to answer questions related to the impact of AD on their health-related quality of life.

AD severity was assessed using Patient Global Assessment (PtGA), where parents or guardians described their child’s eczema severity over the last week as mild, moderate, or severe. The researchers stratified outcomes by geographic region and AD severity, which included the following atopic comorbidities: worst itch, worst skin pain, and overall sleep disturbance in the past 24 hours as measured by the 0-10 numeric rating scale, where higher scores indicate worse severity; eczema-related hospitalization in the past 12 months; and frequency and average duration of flares over the past month.

The mean age of the study participants was 3 years and 61.6% had mild disease. The most common atopic comorbidities were hay fever, asthma, and seasonal allergies, and the incidence of atopic comorbidities increased with increasing AD severity. One or more atopic comorbidities was reported in 88.3% of patients with mild AD, compared with 92.1% of those with moderate disease and 95.8% of those with severe disease. In addition, infants and preschoolers with moderate or severe AD had worse itch, skin pain, and sleep disturbances over the past 24 hours, compared with those who had mild AD.

More than half of infants and preschoolers with severe AD (54.1%) were reported to have been hospitalized in the past 12 months (this ranged from 30.2% to 71.3% across regions), as did 35% of patients with moderate AD and 32.1% of those with mild AD. In addition, 50.6% of infants and preschoolers with severe AD had more than two flares in the past month, compared with 18.1% of those with moderate AD and 6.3% of those with mild disease.

In other findings, 50.7% of infants and preschoolers with severe AD had flares than lasted an average of 2 or more weeks, compared with 20.8% of those with moderate disease and 10% of those with mild disease. Also, 78.3% of preschoolers aged 4 to less than 6 years had missed one or more days of school in the previous 4 weeks: a mean of 5.1 days among those with mild AD, a mean of 7.3 days among those with moderate AD, and a mean of 12.1 days among those with severe disease.

Raj J. Chovatiya MD, PhD, of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that infants and preschoolers remain an understudied group despite the high prevalence of AD in this age range. “The results of this study demonstrate a substantial burden of disease in this population, particularly among those with more severe disease,” said Dr. Chovatiya, who also directs the university’s Center for Eczema and Itch. “This includes longer and more frequent AD flares as well as high rates of inpatient hospitalization. These findings suggest that additional research is needed to better characterize disease burden and optimize outcomes for young children with AD.”

The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Weidinger and other coauthors reported having received institutional research grants and consulting fees from many pharmaceutical companies that manufacture drugs used for the treatment of psoriasis and eczema.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly, EPI Health, Incyte, L’Oréal, the National Eczema Association, Pfizer, Regeneron, Sanofi, and UCB.

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adults with severe asthma (SA) experienced significantly fewer exacerbations on biologic therapies, compared with those who did not use biologics, based on data from more than 2,000 individuals.

The development of biologics to target specific inflammatory pathways “has transformed the management of uncontrolled SA,” but data on the real-world use of biologics in severe asthma patients treated by subspecialists are limited, wrote Reynold A. Panettieri, Jr., MD, of Rutgers, State University of New Jersey, New Brunswick, and colleagues.

In a study published in the Annals of Allergy, Asthma & Immunology, the researchers reviewed data from CHRONICLE, an ongoing, prospective, real-world noninterventional study of adults aged 18 years and older with severe asthma in the United States.

The study population included 2,847 patients enrolled in the CHRONICLE study between February 2018 and February 2021; 68.8% were women, 74.6% were White. The patients ranged in age from 18 to 89 years, with a mean age of 54.2 years.

Biologic use was defined as patients who started or had ongoing use of biologics between 12 months before enrollment and the patient’s most recent data collection. Switches were defined as stopping one biologic and starting another within 6 months; stops were defined as discontinuing a biologic without switching to another within 6 months. A total of 66% of the patients were using biologics at the time of study enrollment. The most common biologic was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), and dupilumab (18%).

Overall, 89% of the patients had ongoing biologic use, 16% had biologic switches, and 13% had stops.

Patients who started biologics or switched biologics had significant reductions in asthma exacerbations at 6 months, compared with nonbiologic users of 58% (1.80 vs. 0.76 per patient-year) and 49% (1.47 vs. 0.75 per patient-year), respectively (P < .001 for both). Asthma exacerbations declined by 70% among biologics users for whom data were available for 12 months before and 12 months after starting biologics.

Exacerbations decreased at 6 months after biologic initiation across all subgroups of patients, notably patients with pre-biologic FEV₁ < 80% and patients with FEV₁ ≥ 80% (66% and 53%, respectively); never smokers and current/former smokers (63% and 50%, respectively); and patients with COPD and without COPD (58% and 52%, respectively).

The researchers also found a greater reduction in exacerbations among patients who switched from anti-IgE therapy to anti–IL-5/IL-5R/IL-4R therapy, compared with those who switched among anti–IL-5/IL-5R/IL-4R therapies (58% vs. 46%).

Patients who stopped or switched biologics appeared to have more severe or treatment-refractory disease than those with ongoing biologic use, the researchers noted. The most common reason for stopping or switching was worsening symptoms.

The study findings were limited by several factors, including the focus only on adults in the United States with subspecialist-treated SA, which may limit generalizability to children or other populations, the researchers noted. Other limitations included the variation in clinical decisions and insurance coverage and the inability to conduct longitudinal assessments, they said.

The results demonstrate that starting or switching biologics was consistently associated with fewer exacerbations in severe asthma. However, more research is needed to determine why some patients were not receiving biologics because they were not considered clinically eligible by their subspecialist health care providers, the researchers concluded.

The current study and the CHRONICLE study were supported by AstraZeneca. Lead author Dr. Panettieri disclosed serving on the advisory boards for and receiving grant support from AstraZeneca, Sanofi, Genentech, Regeneron, and Novartis.

Adults with severe asthma (SA) experienced significantly fewer exacerbations on biologic therapies, compared with those who did not use biologics, based on data from more than 2,000 individuals.

The development of biologics to target specific inflammatory pathways “has transformed the management of uncontrolled SA,” but data on the real-world use of biologics in severe asthma patients treated by subspecialists are limited, wrote Reynold A. Panettieri, Jr., MD, of Rutgers, State University of New Jersey, New Brunswick, and colleagues.

In a study published in the Annals of Allergy, Asthma & Immunology, the researchers reviewed data from CHRONICLE, an ongoing, prospective, real-world noninterventional study of adults aged 18 years and older with severe asthma in the United States.

The study population included 2,847 patients enrolled in the CHRONICLE study between February 2018 and February 2021; 68.8% were women, 74.6% were White. The patients ranged in age from 18 to 89 years, with a mean age of 54.2 years.

Biologic use was defined as patients who started or had ongoing use of biologics between 12 months before enrollment and the patient’s most recent data collection. Switches were defined as stopping one biologic and starting another within 6 months; stops were defined as discontinuing a biologic without switching to another within 6 months. A total of 66% of the patients were using biologics at the time of study enrollment. The most common biologic was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), and dupilumab (18%).

Overall, 89% of the patients had ongoing biologic use, 16% had biologic switches, and 13% had stops.

Patients who started biologics or switched biologics had significant reductions in asthma exacerbations at 6 months, compared with nonbiologic users of 58% (1.80 vs. 0.76 per patient-year) and 49% (1.47 vs. 0.75 per patient-year), respectively (P < .001 for both). Asthma exacerbations declined by 70% among biologics users for whom data were available for 12 months before and 12 months after starting biologics.

Exacerbations decreased at 6 months after biologic initiation across all subgroups of patients, notably patients with pre-biologic FEV₁ < 80% and patients with FEV₁ ≥ 80% (66% and 53%, respectively); never smokers and current/former smokers (63% and 50%, respectively); and patients with COPD and without COPD (58% and 52%, respectively).

The researchers also found a greater reduction in exacerbations among patients who switched from anti-IgE therapy to anti–IL-5/IL-5R/IL-4R therapy, compared with those who switched among anti–IL-5/IL-5R/IL-4R therapies (58% vs. 46%).

Patients who stopped or switched biologics appeared to have more severe or treatment-refractory disease than those with ongoing biologic use, the researchers noted. The most common reason for stopping or switching was worsening symptoms.

The study findings were limited by several factors, including the focus only on adults in the United States with subspecialist-treated SA, which may limit generalizability to children or other populations, the researchers noted. Other limitations included the variation in clinical decisions and insurance coverage and the inability to conduct longitudinal assessments, they said.

The results demonstrate that starting or switching biologics was consistently associated with fewer exacerbations in severe asthma. However, more research is needed to determine why some patients were not receiving biologics because they were not considered clinically eligible by their subspecialist health care providers, the researchers concluded.

The current study and the CHRONICLE study were supported by AstraZeneca. Lead author Dr. Panettieri disclosed serving on the advisory boards for and receiving grant support from AstraZeneca, Sanofi, Genentech, Regeneron, and Novartis.

Adults with severe asthma (SA) experienced significantly fewer exacerbations on biologic therapies, compared with those who did not use biologics, based on data from more than 2,000 individuals.

The development of biologics to target specific inflammatory pathways “has transformed the management of uncontrolled SA,” but data on the real-world use of biologics in severe asthma patients treated by subspecialists are limited, wrote Reynold A. Panettieri, Jr., MD, of Rutgers, State University of New Jersey, New Brunswick, and colleagues.

In a study published in the Annals of Allergy, Asthma & Immunology, the researchers reviewed data from CHRONICLE, an ongoing, prospective, real-world noninterventional study of adults aged 18 years and older with severe asthma in the United States.

The study population included 2,847 patients enrolled in the CHRONICLE study between February 2018 and February 2021; 68.8% were women, 74.6% were White. The patients ranged in age from 18 to 89 years, with a mean age of 54.2 years.

Biologic use was defined as patients who started or had ongoing use of biologics between 12 months before enrollment and the patient’s most recent data collection. Switches were defined as stopping one biologic and starting another within 6 months; stops were defined as discontinuing a biologic without switching to another within 6 months. A total of 66% of the patients were using biologics at the time of study enrollment. The most common biologic was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), and dupilumab (18%).

Overall, 89% of the patients had ongoing biologic use, 16% had biologic switches, and 13% had stops.

Patients who started biologics or switched biologics had significant reductions in asthma exacerbations at 6 months, compared with nonbiologic users of 58% (1.80 vs. 0.76 per patient-year) and 49% (1.47 vs. 0.75 per patient-year), respectively (P < .001 for both). Asthma exacerbations declined by 70% among biologics users for whom data were available for 12 months before and 12 months after starting biologics.

Exacerbations decreased at 6 months after biologic initiation across all subgroups of patients, notably patients with pre-biologic FEV₁ < 80% and patients with FEV₁ ≥ 80% (66% and 53%, respectively); never smokers and current/former smokers (63% and 50%, respectively); and patients with COPD and without COPD (58% and 52%, respectively).

The researchers also found a greater reduction in exacerbations among patients who switched from anti-IgE therapy to anti–IL-5/IL-5R/IL-4R therapy, compared with those who switched among anti–IL-5/IL-5R/IL-4R therapies (58% vs. 46%).

Patients who stopped or switched biologics appeared to have more severe or treatment-refractory disease than those with ongoing biologic use, the researchers noted. The most common reason for stopping or switching was worsening symptoms.

The study findings were limited by several factors, including the focus only on adults in the United States with subspecialist-treated SA, which may limit generalizability to children or other populations, the researchers noted. Other limitations included the variation in clinical decisions and insurance coverage and the inability to conduct longitudinal assessments, they said.

The results demonstrate that starting or switching biologics was consistently associated with fewer exacerbations in severe asthma. However, more research is needed to determine why some patients were not receiving biologics because they were not considered clinically eligible by their subspecialist health care providers, the researchers concluded.

The current study and the CHRONICLE study were supported by AstraZeneca. Lead author Dr. Panettieri disclosed serving on the advisory boards for and receiving grant support from AstraZeneca, Sanofi, Genentech, Regeneron, and Novartis.

Adding salt to food at the table was linked to a higher risk of premature death and a lower life expectancy, independent of diet, lifestyle, socioeconomic level, and pre-existing diseases, in a new study.

In the study of more than 500,000 people, compared with those who never or rarely added salt, those who always added salt to their food had a 28% increased risk of dying prematurely (defined as death before the age of 75 years).

Results also showed that adding salt to food was linked to a lower life expectancy. At the age of 50 years, life expectancy was reduced by 1.5 years in women and by 2.28 years in men who always added salt to their food, compared with those who never or rarely did.

However, these increased risks appeared to be attenuated with increasing intakes of high-potassium foods (vegetables and fruits).

The study was published online in the European Heart Journal.

“As far as we are aware, this is the first study to analyze adding salt to meals as a unique measurement for dietary sodium intake. Such a measure is less likely affected by other dietary components, especially potassium intake,” senior author Lu Qi, MD, Tulane University, New Orleans, told this news organization.

“Our study provides supportive evidence from a novel perspective to show the adverse effects of high sodium intake on human health, which is still a controversial topic. Our findings support the advice that reduction of salt intake by reducing the salt added to meals may benefit health and improve life expectancy. Our results also suggest that high intakes of fruits and vegetables are beneficial regarding lowering the adverse effects of salt,” he added.
 

Link between dietary salt and health is subject of longstanding debate

The researchers explained that the relationship between dietary salt intake and health remains a subject of longstanding debate, with previous studies on the association between sodium intake and mortality having shown conflicting results.

They attributed the inconsistent results to the low accuracy of sodium measurement, noting that sodium intake varies widely from day to day, but the majority of previous studies have largely relied on a single day’s urine collection or dietary survey for estimating the sodium intake, which is inadequate to assess an individual’s usual consumption levels.

They also pointed out that it is difficult to separate the contributions of intakes of sodium and potassium to health based on current methods for measuring dietary sodium and  potassium, and this may confound the association between sodium intake and health outcomes.

They noted that the hypothesis that a high-potassium intake may attenuate the adverse association of high-sodium intake with health outcomes has been proposed for many years, but studies assessing the interaction between sodium intake and potassium intake on the risk of mortality are scarce.

Adding salt to food at the table is a common eating behavior directly related to an individual’s long-term preference for salty tasting foods and habitual salt intake, the authors said, adding that commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors including potassium. “Therefore, adding salt to foods provides a unique assessment to evaluate the association between habitual sodium intake and mortality.”
 

UK Biobank study

For the current study Dr. Qi and colleagues analyzed data from 501,379 people taking part in the UK Biobank study. When joining the study between 2006 and 2010, the participants were asked whether they added salt to their foods never/rarely, sometimes, usually or always. Participants were then followed for a median of 9 years.

After adjustment for sex, age, race, smoking, moderate drinking, body mass index, physical activity, Townsend deprivation index, high cholesterol, chronic kidney disease, diabetes, cardiovascular disease, and cancer, results showed an increasing risk of all-cause premature mortality rose with increasing frequency of adding salt to foods.

The adjusted hazard ratios, compared with those who never or rarely added salt, were 1.02 (95% CI, 0.99-1.06) for those who added salt sometimes, 1.07 (95% CI, 1.02-1.11) for those who usually added salt, and 1.28 (95% CI, 1.20-1.35) for those who always added salt.

The researchers also estimated the lower survival time caused by the high frequency of adding salt to foods. At age 50, women who always added salt to foods had an average 1.50 fewer years of life expectancy, and men who always added salt had an average 2.28 fewer years of life expectancy, as compared with their counterparts who never/rarely added salt to foods.

For cause-specific premature mortality, results showed that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular mortality and cancer mortality, but not for dementia mortality or respiratory mortality. For the subtypes of cardiovascular mortality, adding salt to foods was significantly associated with higher risk of stroke mortality but not coronary heart disease mortality.

Other analyses suggested that the association of adding salt to foods with an increased risk of premature mortality appeared to be attenuated with increasing intake of food high in potassium (fruits and vegetables).

The authors point out that the amounts of discretionary sodium intake (the salt used at the table or in home cooking) have been largely overlooked in previous studies, even though adding salt to foods accounts for a considerable proportion of total sodium intake (6%-20%) in Western diets.

“Our findings also support the notion that even a modest reduction in sodium intake is likely to result in substantial health benefits, especially when it is achieved in the general population,” they conclude.
 

Conflicting information from different studies

But the current findings seem to directly contradict those from another recent study by Messerli and colleagues showing higher sodium intake correlates with improved life expectancy.

Addressing these contradictory results, Dr. Qi commented: “The study of Messerli et al. is based on an ecological design, in which the analysis is performed on country average sodium intake, rather than at the individual level. This type of ecological study has several major limitations, such as the lack of individuals’ sodium intake, uncontrolled confounding, and the cross-sectional nature. Typically, ecological studies are not considered useful for testing hypothesis in epidemiological studies.”

Dr. Qi noted that, in contrast, his current study analyzes individuals’ exposure, and has a prospective design. “Our findings are supported by previous large-scale observational studies and clinical trials which show the high intake of sodium may adversely affect chronic diseases such as cardiovascular disease and hypertension.” =

Lead author of the ecological study, Franz Messerli, MD, Bern (Switzerland) University Hospital, however, was not convinced by the findings from Dr. Qi’s study.

“The difference in 24-hour sodium intake between those who never/rarely added salt and those who always did is a minuscule 0.17 g. It is highly unlikely that such negligible quantity has any impact on blood pressure, not to mention cardiovascular mortality or life expectancy,” he commented in an interview.

He also pointed out that, in Dr. Qi’s study, people who added salt more frequently also consumed more red meat and processed meat, as well as less fish and less fruit and vegetables. “I would suggest that the bad habit of adding salt at the table is simply a powerful marker for an unhealthy diet.”

“There is no question that an excessive salt intake is harmful in hypertensive patients and increases the risk of stroke. But 0.17 g is not going to make any difference,” Dr. Messerli added.
 

What is the optimum level?

In an editorial accompanying the study by Dr. Qi and colleagues in the European Heart Journal, Annika Rosengren, MD, PhD, Sahlgrenska University Hospital, Gothenburg, Sweden, noted that guidelines recommend a salt intake below 5 g, or about a teaspoon, per day. But few individuals meet this recommendation.

Because several recent studies show a U- or J-shaped association between salt and atherosclerotic cardiovascular disease, reducing salt intake across the whole population may not be universally beneficial, Dr. Rosengren said.

“So far, what the collective evidence about salt seems to indicate is that healthy people consuming what constitutes normal levels of ordinary salt need not worry too much about their salt intake,” she wrote.

Instead, she advised a diet rich in fruit and vegetables should be a priority to counterbalance potentially harmful effects of salt, and for many other reasons.

And she added that people at high risk, such as those with hypertension who have a high salt intake, are probably well advised to cut down, and not adding extra salt to already prepared foods is one way of achieving this. However, at the individual level, the optimal salt consumption range, or the “sweet spot” remains to be determined. 

“Not adding extra salt to food is unlikely to be harmful and could contribute to strategies to lower population blood pressure levels,” Dr. Rosengren concluded.

A version of this article first appeared on Medscape.com.

Adding salt to food at the table was linked to a higher risk of premature death and a lower life expectancy, independent of diet, lifestyle, socioeconomic level, and pre-existing diseases, in a new study.

In the study of more than 500,000 people, compared with those who never or rarely added salt, those who always added salt to their food had a 28% increased risk of dying prematurely (defined as death before the age of 75 years).

Results also showed that adding salt to food was linked to a lower life expectancy. At the age of 50 years, life expectancy was reduced by 1.5 years in women and by 2.28 years in men who always added salt to their food, compared with those who never or rarely did.

However, these increased risks appeared to be attenuated with increasing intakes of high-potassium foods (vegetables and fruits).

The study was published online in the European Heart Journal.

“As far as we are aware, this is the first study to analyze adding salt to meals as a unique measurement for dietary sodium intake. Such a measure is less likely affected by other dietary components, especially potassium intake,” senior author Lu Qi, MD, Tulane University, New Orleans, told this news organization.

“Our study provides supportive evidence from a novel perspective to show the adverse effects of high sodium intake on human health, which is still a controversial topic. Our findings support the advice that reduction of salt intake by reducing the salt added to meals may benefit health and improve life expectancy. Our results also suggest that high intakes of fruits and vegetables are beneficial regarding lowering the adverse effects of salt,” he added.
 

Link between dietary salt and health is subject of longstanding debate

The researchers explained that the relationship between dietary salt intake and health remains a subject of longstanding debate, with previous studies on the association between sodium intake and mortality having shown conflicting results.

They attributed the inconsistent results to the low accuracy of sodium measurement, noting that sodium intake varies widely from day to day, but the majority of previous studies have largely relied on a single day’s urine collection or dietary survey for estimating the sodium intake, which is inadequate to assess an individual’s usual consumption levels.

They also pointed out that it is difficult to separate the contributions of intakes of sodium and potassium to health based on current methods for measuring dietary sodium and  potassium, and this may confound the association between sodium intake and health outcomes.

They noted that the hypothesis that a high-potassium intake may attenuate the adverse association of high-sodium intake with health outcomes has been proposed for many years, but studies assessing the interaction between sodium intake and potassium intake on the risk of mortality are scarce.

Adding salt to food at the table is a common eating behavior directly related to an individual’s long-term preference for salty tasting foods and habitual salt intake, the authors said, adding that commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors including potassium. “Therefore, adding salt to foods provides a unique assessment to evaluate the association between habitual sodium intake and mortality.”
 

UK Biobank study

For the current study Dr. Qi and colleagues analyzed data from 501,379 people taking part in the UK Biobank study. When joining the study between 2006 and 2010, the participants were asked whether they added salt to their foods never/rarely, sometimes, usually or always. Participants were then followed for a median of 9 years.

After adjustment for sex, age, race, smoking, moderate drinking, body mass index, physical activity, Townsend deprivation index, high cholesterol, chronic kidney disease, diabetes, cardiovascular disease, and cancer, results showed an increasing risk of all-cause premature mortality rose with increasing frequency of adding salt to foods.

The adjusted hazard ratios, compared with those who never or rarely added salt, were 1.02 (95% CI, 0.99-1.06) for those who added salt sometimes, 1.07 (95% CI, 1.02-1.11) for those who usually added salt, and 1.28 (95% CI, 1.20-1.35) for those who always added salt.

The researchers also estimated the lower survival time caused by the high frequency of adding salt to foods. At age 50, women who always added salt to foods had an average 1.50 fewer years of life expectancy, and men who always added salt had an average 2.28 fewer years of life expectancy, as compared with their counterparts who never/rarely added salt to foods.

For cause-specific premature mortality, results showed that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular mortality and cancer mortality, but not for dementia mortality or respiratory mortality. For the subtypes of cardiovascular mortality, adding salt to foods was significantly associated with higher risk of stroke mortality but not coronary heart disease mortality.

Other analyses suggested that the association of adding salt to foods with an increased risk of premature mortality appeared to be attenuated with increasing intake of food high in potassium (fruits and vegetables).

The authors point out that the amounts of discretionary sodium intake (the salt used at the table or in home cooking) have been largely overlooked in previous studies, even though adding salt to foods accounts for a considerable proportion of total sodium intake (6%-20%) in Western diets.

“Our findings also support the notion that even a modest reduction in sodium intake is likely to result in substantial health benefits, especially when it is achieved in the general population,” they conclude.
 

Conflicting information from different studies

But the current findings seem to directly contradict those from another recent study by Messerli and colleagues showing higher sodium intake correlates with improved life expectancy.

Addressing these contradictory results, Dr. Qi commented: “The study of Messerli et al. is based on an ecological design, in which the analysis is performed on country average sodium intake, rather than at the individual level. This type of ecological study has several major limitations, such as the lack of individuals’ sodium intake, uncontrolled confounding, and the cross-sectional nature. Typically, ecological studies are not considered useful for testing hypothesis in epidemiological studies.”

Dr. Qi noted that, in contrast, his current study analyzes individuals’ exposure, and has a prospective design. “Our findings are supported by previous large-scale observational studies and clinical trials which show the high intake of sodium may adversely affect chronic diseases such as cardiovascular disease and hypertension.” =

Lead author of the ecological study, Franz Messerli, MD, Bern (Switzerland) University Hospital, however, was not convinced by the findings from Dr. Qi’s study.

“The difference in 24-hour sodium intake between those who never/rarely added salt and those who always did is a minuscule 0.17 g. It is highly unlikely that such negligible quantity has any impact on blood pressure, not to mention cardiovascular mortality or life expectancy,” he commented in an interview.

He also pointed out that, in Dr. Qi’s study, people who added salt more frequently also consumed more red meat and processed meat, as well as less fish and less fruit and vegetables. “I would suggest that the bad habit of adding salt at the table is simply a powerful marker for an unhealthy diet.”

“There is no question that an excessive salt intake is harmful in hypertensive patients and increases the risk of stroke. But 0.17 g is not going to make any difference,” Dr. Messerli added.
 

What is the optimum level?

In an editorial accompanying the study by Dr. Qi and colleagues in the European Heart Journal, Annika Rosengren, MD, PhD, Sahlgrenska University Hospital, Gothenburg, Sweden, noted that guidelines recommend a salt intake below 5 g, or about a teaspoon, per day. But few individuals meet this recommendation.

Because several recent studies show a U- or J-shaped association between salt and atherosclerotic cardiovascular disease, reducing salt intake across the whole population may not be universally beneficial, Dr. Rosengren said.

“So far, what the collective evidence about salt seems to indicate is that healthy people consuming what constitutes normal levels of ordinary salt need not worry too much about their salt intake,” she wrote.

Instead, she advised a diet rich in fruit and vegetables should be a priority to counterbalance potentially harmful effects of salt, and for many other reasons.

And she added that people at high risk, such as those with hypertension who have a high salt intake, are probably well advised to cut down, and not adding extra salt to already prepared foods is one way of achieving this. However, at the individual level, the optimal salt consumption range, or the “sweet spot” remains to be determined. 

“Not adding extra salt to food is unlikely to be harmful and could contribute to strategies to lower population blood pressure levels,” Dr. Rosengren concluded.

A version of this article first appeared on Medscape.com.

Adding salt to food at the table was linked to a higher risk of premature death and a lower life expectancy, independent of diet, lifestyle, socioeconomic level, and pre-existing diseases, in a new study.

In the study of more than 500,000 people, compared with those who never or rarely added salt, those who always added salt to their food had a 28% increased risk of dying prematurely (defined as death before the age of 75 years).

Results also showed that adding salt to food was linked to a lower life expectancy. At the age of 50 years, life expectancy was reduced by 1.5 years in women and by 2.28 years in men who always added salt to their food, compared with those who never or rarely did.

However, these increased risks appeared to be attenuated with increasing intakes of high-potassium foods (vegetables and fruits).

The study was published online in the European Heart Journal.

“As far as we are aware, this is the first study to analyze adding salt to meals as a unique measurement for dietary sodium intake. Such a measure is less likely affected by other dietary components, especially potassium intake,” senior author Lu Qi, MD, Tulane University, New Orleans, told this news organization.

“Our study provides supportive evidence from a novel perspective to show the adverse effects of high sodium intake on human health, which is still a controversial topic. Our findings support the advice that reduction of salt intake by reducing the salt added to meals may benefit health and improve life expectancy. Our results also suggest that high intakes of fruits and vegetables are beneficial regarding lowering the adverse effects of salt,” he added.
 

Link between dietary salt and health is subject of longstanding debate

The researchers explained that the relationship between dietary salt intake and health remains a subject of longstanding debate, with previous studies on the association between sodium intake and mortality having shown conflicting results.

They attributed the inconsistent results to the low accuracy of sodium measurement, noting that sodium intake varies widely from day to day, but the majority of previous studies have largely relied on a single day’s urine collection or dietary survey for estimating the sodium intake, which is inadequate to assess an individual’s usual consumption levels.

They also pointed out that it is difficult to separate the contributions of intakes of sodium and potassium to health based on current methods for measuring dietary sodium and  potassium, and this may confound the association between sodium intake and health outcomes.

They noted that the hypothesis that a high-potassium intake may attenuate the adverse association of high-sodium intake with health outcomes has been proposed for many years, but studies assessing the interaction between sodium intake and potassium intake on the risk of mortality are scarce.

Adding salt to food at the table is a common eating behavior directly related to an individual’s long-term preference for salty tasting foods and habitual salt intake, the authors said, adding that commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors including potassium. “Therefore, adding salt to foods provides a unique assessment to evaluate the association between habitual sodium intake and mortality.”
 

UK Biobank study

For the current study Dr. Qi and colleagues analyzed data from 501,379 people taking part in the UK Biobank study. When joining the study between 2006 and 2010, the participants were asked whether they added salt to their foods never/rarely, sometimes, usually or always. Participants were then followed for a median of 9 years.

After adjustment for sex, age, race, smoking, moderate drinking, body mass index, physical activity, Townsend deprivation index, high cholesterol, chronic kidney disease, diabetes, cardiovascular disease, and cancer, results showed an increasing risk of all-cause premature mortality rose with increasing frequency of adding salt to foods.

The adjusted hazard ratios, compared with those who never or rarely added salt, were 1.02 (95% CI, 0.99-1.06) for those who added salt sometimes, 1.07 (95% CI, 1.02-1.11) for those who usually added salt, and 1.28 (95% CI, 1.20-1.35) for those who always added salt.

The researchers also estimated the lower survival time caused by the high frequency of adding salt to foods. At age 50, women who always added salt to foods had an average 1.50 fewer years of life expectancy, and men who always added salt had an average 2.28 fewer years of life expectancy, as compared with their counterparts who never/rarely added salt to foods.

For cause-specific premature mortality, results showed that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular mortality and cancer mortality, but not for dementia mortality or respiratory mortality. For the subtypes of cardiovascular mortality, adding salt to foods was significantly associated with higher risk of stroke mortality but not coronary heart disease mortality.

Other analyses suggested that the association of adding salt to foods with an increased risk of premature mortality appeared to be attenuated with increasing intake of food high in potassium (fruits and vegetables).

The authors point out that the amounts of discretionary sodium intake (the salt used at the table or in home cooking) have been largely overlooked in previous studies, even though adding salt to foods accounts for a considerable proportion of total sodium intake (6%-20%) in Western diets.

“Our findings also support the notion that even a modest reduction in sodium intake is likely to result in substantial health benefits, especially when it is achieved in the general population,” they conclude.
 

Conflicting information from different studies

But the current findings seem to directly contradict those from another recent study by Messerli and colleagues showing higher sodium intake correlates with improved life expectancy.

Addressing these contradictory results, Dr. Qi commented: “The study of Messerli et al. is based on an ecological design, in which the analysis is performed on country average sodium intake, rather than at the individual level. This type of ecological study has several major limitations, such as the lack of individuals’ sodium intake, uncontrolled confounding, and the cross-sectional nature. Typically, ecological studies are not considered useful for testing hypothesis in epidemiological studies.”

Dr. Qi noted that, in contrast, his current study analyzes individuals’ exposure, and has a prospective design. “Our findings are supported by previous large-scale observational studies and clinical trials which show the high intake of sodium may adversely affect chronic diseases such as cardiovascular disease and hypertension.” =

Lead author of the ecological study, Franz Messerli, MD, Bern (Switzerland) University Hospital, however, was not convinced by the findings from Dr. Qi’s study.

“The difference in 24-hour sodium intake between those who never/rarely added salt and those who always did is a minuscule 0.17 g. It is highly unlikely that such negligible quantity has any impact on blood pressure, not to mention cardiovascular mortality or life expectancy,” he commented in an interview.

He also pointed out that, in Dr. Qi’s study, people who added salt more frequently also consumed more red meat and processed meat, as well as less fish and less fruit and vegetables. “I would suggest that the bad habit of adding salt at the table is simply a powerful marker for an unhealthy diet.”

“There is no question that an excessive salt intake is harmful in hypertensive patients and increases the risk of stroke. But 0.17 g is not going to make any difference,” Dr. Messerli added.
 

What is the optimum level?

In an editorial accompanying the study by Dr. Qi and colleagues in the European Heart Journal, Annika Rosengren, MD, PhD, Sahlgrenska University Hospital, Gothenburg, Sweden, noted that guidelines recommend a salt intake below 5 g, or about a teaspoon, per day. But few individuals meet this recommendation.

Because several recent studies show a U- or J-shaped association between salt and atherosclerotic cardiovascular disease, reducing salt intake across the whole population may not be universally beneficial, Dr. Rosengren said.

“So far, what the collective evidence about salt seems to indicate is that healthy people consuming what constitutes normal levels of ordinary salt need not worry too much about their salt intake,” she wrote.

Instead, she advised a diet rich in fruit and vegetables should be a priority to counterbalance potentially harmful effects of salt, and for many other reasons.

And she added that people at high risk, such as those with hypertension who have a high salt intake, are probably well advised to cut down, and not adding extra salt to already prepared foods is one way of achieving this. However, at the individual level, the optimal salt consumption range, or the “sweet spot” remains to be determined. 

“Not adding extra salt to food is unlikely to be harmful and could contribute to strategies to lower population blood pressure levels,” Dr. Rosengren concluded.

A version of this article first appeared on Medscape.com.

A retrospective investigation using medical claims data found no elevated risk of disease flares in patients with immune-mediated inflammatory diseases (IMIDs) who received the recombinant zoster vaccine (RZV), according to research published in Arthritis & Rheumatology.

The authors of the study noted that individuals with IMIDs are at increased risk for herpes zoster and related complications, including postherpetic neuralgia, and that vaccination has been recommended for certain groups of patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis, by the American College of Rheumatology and other professional organizations for individuals aged 50 and older.

The study investigators used medical claims from IBM MarketScan, which provided data on patients aged 50-64 years, and data from the Centers for Medicare and Medicaid Services’ Medicare on patients aged 65 and older.

They defined presumed flares in three ways: hospitalization/emergency department visits for IMIDs, steroid treatment with a short-acting oral glucocorticoid, or treatment with a parenteral glucocorticoid injection. The investigators conducted a self-controlled case series (SCCS) analysis to examine any temporal link between the RZV and disease flares.

Among enrollees with IMIDs, 14.8% of the 55,654 patients in the MarketScan database and 43.2% of the 160,545 patients in the Medicare database received at least one dose of RZV during 2018-2019. The two-dose series completion within 6 months was 76.6% in the MarketScan group (age range, 50-64 years) and 85.4% among Medicare enrollees (age range, 65 years and older). In the SCCS analysis, 10% and 13% of patients developed flares in the control group as compared to 9%, and 11%-12% in the risk window following one or two doses of RZV among MarketScan and Medicare enrollees, respectively.

Based on these findings, the investigators concluded there was no statistically significant increase in flares subsequent to RZV administration for any IMID in either patients aged 50-64 years or patients aged 65 years and older following the first dose or second dose.

Nilanjana Bose, MD, a rheumatologist with Lonestar Rheumatology, Houston, Texas, who was not involved with the study, said that the research addresses a topic where there is uneasiness, namely vaccination in patients with IMIDs.

A retrospective investigation using medical claims data found no elevated risk of disease flares in patients with immune-mediated inflammatory diseases (IMIDs) who received the recombinant zoster vaccine (RZV), according to research published in Arthritis & Rheumatology.

The authors of the study noted that individuals with IMIDs are at increased risk for herpes zoster and related complications, including postherpetic neuralgia, and that vaccination has been recommended for certain groups of patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis, by the American College of Rheumatology and other professional organizations for individuals aged 50 and older.

The study investigators used medical claims from IBM MarketScan, which provided data on patients aged 50-64 years, and data from the Centers for Medicare and Medicaid Services’ Medicare on patients aged 65 and older.

They defined presumed flares in three ways: hospitalization/emergency department visits for IMIDs, steroid treatment with a short-acting oral glucocorticoid, or treatment with a parenteral glucocorticoid injection. The investigators conducted a self-controlled case series (SCCS) analysis to examine any temporal link between the RZV and disease flares.

Among enrollees with IMIDs, 14.8% of the 55,654 patients in the MarketScan database and 43.2% of the 160,545 patients in the Medicare database received at least one dose of RZV during 2018-2019. The two-dose series completion within 6 months was 76.6% in the MarketScan group (age range, 50-64 years) and 85.4% among Medicare enrollees (age range, 65 years and older). In the SCCS analysis, 10% and 13% of patients developed flares in the control group as compared to 9%, and 11%-12% in the risk window following one or two doses of RZV among MarketScan and Medicare enrollees, respectively.

Based on these findings, the investigators concluded there was no statistically significant increase in flares subsequent to RZV administration for any IMID in either patients aged 50-64 years or patients aged 65 years and older following the first dose or second dose.

Nilanjana Bose, MD, a rheumatologist with Lonestar Rheumatology, Houston, Texas, who was not involved with the study, said that the research addresses a topic where there is uneasiness, namely vaccination in patients with IMIDs.

A retrospective investigation using medical claims data found no elevated risk of disease flares in patients with immune-mediated inflammatory diseases (IMIDs) who received the recombinant zoster vaccine (RZV), according to research published in Arthritis & Rheumatology.

The authors of the study noted that individuals with IMIDs are at increased risk for herpes zoster and related complications, including postherpetic neuralgia, and that vaccination has been recommended for certain groups of patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis, by the American College of Rheumatology and other professional organizations for individuals aged 50 and older.

The study investigators used medical claims from IBM MarketScan, which provided data on patients aged 50-64 years, and data from the Centers for Medicare and Medicaid Services’ Medicare on patients aged 65 and older.

They defined presumed flares in three ways: hospitalization/emergency department visits for IMIDs, steroid treatment with a short-acting oral glucocorticoid, or treatment with a parenteral glucocorticoid injection. The investigators conducted a self-controlled case series (SCCS) analysis to examine any temporal link between the RZV and disease flares.

Among enrollees with IMIDs, 14.8% of the 55,654 patients in the MarketScan database and 43.2% of the 160,545 patients in the Medicare database received at least one dose of RZV during 2018-2019. The two-dose series completion within 6 months was 76.6% in the MarketScan group (age range, 50-64 years) and 85.4% among Medicare enrollees (age range, 65 years and older). In the SCCS analysis, 10% and 13% of patients developed flares in the control group as compared to 9%, and 11%-12% in the risk window following one or two doses of RZV among MarketScan and Medicare enrollees, respectively.

Based on these findings, the investigators concluded there was no statistically significant increase in flares subsequent to RZV administration for any IMID in either patients aged 50-64 years or patients aged 65 years and older following the first dose or second dose.

Nilanjana Bose, MD, a rheumatologist with Lonestar Rheumatology, Houston, Texas, who was not involved with the study, said that the research addresses a topic where there is uneasiness, namely vaccination in patients with IMIDs.

California Gov. Gavin Newsom says the state government will manufacture its own low-cost insulin to make the drug more affordable for residents.

On July 7, he said he had just signed a state budget that includes $50 million for development of the insulin and another $50 million for a place to make it.

“Nothing, nothing epitomizes market failures more than the cost of insulin,” Gov. Newsom said in a video posted on the governor’s Twitter page. He noted that many Americans have out-of-pocket costs ranging from $300 to $500 per month for insulin, which is used to treat diabetes.

“In California, we know people should not go into debt to receive lifesaving medication,” he said.

Gov. Newsom said that when he first took office, he signed an executive order to launch California’s own prescription drug system and that the insulin initiative is the first step toward making that happen.

People who take insulin have long complained about its high price. A November 2021 report from The Lancet said 25% of the insulin patients in the United States struggle to pay for it.

The cost of insulin for patients with insurance ranges from $334 to $1,000 a month, ABC News said, citing the Kaiser Family Foundation.

Legislation in Congress would bring down the cost of insulin if passed, with one bill capping costs at $35 per month for patients with health insurance. But The Hill reported that some Republicans oppose the legislation because it would interfere with free markets and raise costs for drug companies.

The CDC says 37.3 million people in the United States – about 11.3% of the population – have diabetes, with 8.5 million of them undiagnosed.

A version of this article first appeared on WebMD.com.

California Gov. Gavin Newsom says the state government will manufacture its own low-cost insulin to make the drug more affordable for residents.

On July 7, he said he had just signed a state budget that includes $50 million for development of the insulin and another $50 million for a place to make it.

“Nothing, nothing epitomizes market failures more than the cost of insulin,” Gov. Newsom said in a video posted on the governor’s Twitter page. He noted that many Americans have out-of-pocket costs ranging from $300 to $500 per month for insulin, which is used to treat diabetes.

“In California, we know people should not go into debt to receive lifesaving medication,” he said.

Gov. Newsom said that when he first took office, he signed an executive order to launch California’s own prescription drug system and that the insulin initiative is the first step toward making that happen.

People who take insulin have long complained about its high price. A November 2021 report from The Lancet said 25% of the insulin patients in the United States struggle to pay for it.

The cost of insulin for patients with insurance ranges from $334 to $1,000 a month, ABC News said, citing the Kaiser Family Foundation.

Legislation in Congress would bring down the cost of insulin if passed, with one bill capping costs at $35 per month for patients with health insurance. But The Hill reported that some Republicans oppose the legislation because it would interfere with free markets and raise costs for drug companies.

The CDC says 37.3 million people in the United States – about 11.3% of the population – have diabetes, with 8.5 million of them undiagnosed.

A version of this article first appeared on WebMD.com.

California Gov. Gavin Newsom says the state government will manufacture its own low-cost insulin to make the drug more affordable for residents.

On July 7, he said he had just signed a state budget that includes $50 million for development of the insulin and another $50 million for a place to make it.

“Nothing, nothing epitomizes market failures more than the cost of insulin,” Gov. Newsom said in a video posted on the governor’s Twitter page. He noted that many Americans have out-of-pocket costs ranging from $300 to $500 per month for insulin, which is used to treat diabetes.

“In California, we know people should not go into debt to receive lifesaving medication,” he said.

Gov. Newsom said that when he first took office, he signed an executive order to launch California’s own prescription drug system and that the insulin initiative is the first step toward making that happen.

People who take insulin have long complained about its high price. A November 2021 report from The Lancet said 25% of the insulin patients in the United States struggle to pay for it.

The cost of insulin for patients with insurance ranges from $334 to $1,000 a month, ABC News said, citing the Kaiser Family Foundation.

Legislation in Congress would bring down the cost of insulin if passed, with one bill capping costs at $35 per month for patients with health insurance. But The Hill reported that some Republicans oppose the legislation because it would interfere with free markets and raise costs for drug companies.

The CDC says 37.3 million people in the United States – about 11.3% of the population – have diabetes, with 8.5 million of them undiagnosed.

A version of this article first appeared on WebMD.com.

A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.

Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.

Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.

The study was published online in Gastroenterology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.

Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.

One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.

To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.

The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.

The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.

In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.

There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.

The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.

The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.

The researchers have no relevant financial disclosures.

A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.

Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.

Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.

The study was published online in Gastroenterology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.

Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.

One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.

To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.

The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.

The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.

In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.

There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.

The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.

The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.

The researchers have no relevant financial disclosures.

A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.

Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.

Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.

The study was published online in Gastroenterology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.

Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.

One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.

To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.

The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.

The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.

In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.

There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.

The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.

The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.

The researchers have no relevant financial disclosures.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.