Asthma

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

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

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

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

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

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

The risk of bullying and teasing is higher in children and young people with poorer asthma control, an international study reported. Published online in the Archives of Disease in Childhood, the Room to Breathe survey of 943 children in six countries found 9.9% had experienced asthma-related bullying or teasing (n = 93).

Children with well-controlled disease, however, were less likely to report being victimized by asthma-related bullying/teasing: odds ratio, 0.51; 95% confidence interval, 0.23-0.84; P = .006).

“It’s important for pediatricians to recognize that children and young people with asthma commonly report bullying or teasing as a result of their condition,” Will Carroll, MD, of the Paediatric Respiratory Service at Staffordshire Children’s Hospital at Royal Stoke, Stoke-on-Trent, England, told this news organization. “Pediatricians should talk to children themselves with asthma about this and not just their parents, and efforts should be made to improve asthma control whenever possible.”

Though common and potentially long-lasting in its effects, bullying is rarely addressed by health care professionals, the U.K. authors said.

But things may differ in the United States. According to Mark Welles, MD, a pediatrician at Cohen Children’s Medical Center at Northwell Health in Queen’s, N.Y., and regional cochair of the American Academy of Pediatrics antibullying committee, young doctors here are trained to ask about bullying when seeing a child, no matter what the reason for the visit. “It’s important to build a rapport with the child, and you need to ask about the disease they may have but also generally ask, ‘How are things at school? Is everyone nice to you?’ It is becoming more common practice to ask this,” said Dr. Welles, who was not involved with the U.K. research.

The U.K. study drew on unpublished data from the Room to Breathe survey conducted by Dr. Carroll’s group during 2008-2009 in Canada, the United Kingdom, Greece, Hungary, South Africa, and the Netherlands. Only 358 of 930 (38.5%) children were found to be well controlled according to current Global Initiative for Asthma symptom-control criteria.

The analysis also found a highly significant association (P < .0001) between Childhood Asthma Control Test (C-ACT) score and reported bullying/teasing, with bullied children having lower scores. C-ACT–defined controlled asthma scores of 20 or higher were significantly associated with a lower risk of bullying (OR, 0.46; 95% CI, 0.28-0.76; P = .001).

In other study findings, harassment was more common in children whose asthma was serious enough to entail activity restriction (OR, 1.74; 95% CI, 1.11-2.75; P = .010) and who described their asthma as “bad” (OR, 3.02; 95% CI, 1.86-4.85; P < .001), as well as those whose parents reported ongoing asthma-related health worries (OR, 1.64; 95% CI, 1.04-2.58; P = .024).

“When a child is clearly different from others, such as having bad asthma or being limited in activities due to asthma, they stand out more and are more frequently bullied,” said Tracy Evian Waasdorp, PhD, MSEd, director of research for school-based bullying and social-emotional learning at Children’s Hospital of Philadelphia, and also not a participant in the U.K. study.

In contrast to the 10% bullying rate in Dr. Carroll’s study, Dr. Waasdorp referred to a CHOP analysis of more than 64,000 youth from a Northeastern state in which those with asthma were 40% more likely to be victims of in-person bullying and 70% were more likely to be cyberbullied than youth without asthma. “Having a medical condition can therefore put you at risk of being bullied regardless of what country you live in,” she said.

CHOP policy encourages practitioners to routinely ask about bullying and to provide handouts and resources for parents, she added.

Interestingly, the U.K. investigators found that open public use of spacers was not associated with asthma-related bullying, nor was parental worry at diagnosis or parental concern about steroid use.

But according to Dr. Welles, “Kids may be using the inhaler in front of other kids, and they may be embarrassed and not want to be seen as different. So they may not use the inhaler when needed for gym class or sports, forcing them to sit out and then potentially be bullied again. It’s a vicious cycle.”

Previous research has identified the bullying and teasing of children with food allergies.

Behaviors have included allergy-specific harassment such as smearing peanut butter on a youngster’s forehead or putting peanut butter cookie crumbs in a child’s lunch box.

“In our survey we asked the question ‘Have you been teased or bullied because of your asthma?’ but we didn’t ask what form this took,” Dr. Carroll said. “But we were surprised at just how many children said yes. It’s time for more research, I think.”

“There are never enough studies around this,” added Dr. Welles. “Bullying, whether because of asthma or otherwise, has the potential for long-term effects well into adulthood.”

In the meantime, asthma consultations should incorporate specific questions about bullying. They should also be child focused in order to gain a representative appreciation of asthma control and its effect on the child’s life.

“As pediatricians, we need to be continuously supporting parents and find the help they need to address any mental health issues,” Dr. Welles said. “Every pediatrician and parent needs to be aware and recognize when something is different in their child’s life. Please don’t ignore it.”

Dr. Waasdorp stressed that school and other communities should be aware that children with asthma may be at increased risk for aggression and harmful interactions related to their asthma. “Programming to reduce bullying should focus broadly on shifting the climate so that bullying is not perceived to be normative and on improving ‘upstander,’ or positive bystander, responses.” she said.

The original survey was funded by Nycomed (Zurich). No additional funding was requested for the current analysis. Dr. Carroll reported personal fees from GlaxoSmithKline, Novartis, and Trudell Medical International outside the submitted work. Dr. Welles and Dr. Waasdorp disclosed no competing interests relevant to their comments.

The risk of bullying and teasing is higher in children and young people with poorer asthma control, an international study reported. Published online in the Archives of Disease in Childhood, the Room to Breathe survey of 943 children in six countries found 9.9% had experienced asthma-related bullying or teasing (n = 93).

Children with well-controlled disease, however, were less likely to report being victimized by asthma-related bullying/teasing: odds ratio, 0.51; 95% confidence interval, 0.23-0.84; P = .006).

“It’s important for pediatricians to recognize that children and young people with asthma commonly report bullying or teasing as a result of their condition,” Will Carroll, MD, of the Paediatric Respiratory Service at Staffordshire Children’s Hospital at Royal Stoke, Stoke-on-Trent, England, told this news organization. “Pediatricians should talk to children themselves with asthma about this and not just their parents, and efforts should be made to improve asthma control whenever possible.”

Though common and potentially long-lasting in its effects, bullying is rarely addressed by health care professionals, the U.K. authors said.

But things may differ in the United States. According to Mark Welles, MD, a pediatrician at Cohen Children’s Medical Center at Northwell Health in Queen’s, N.Y., and regional cochair of the American Academy of Pediatrics antibullying committee, young doctors here are trained to ask about bullying when seeing a child, no matter what the reason for the visit. “It’s important to build a rapport with the child, and you need to ask about the disease they may have but also generally ask, ‘How are things at school? Is everyone nice to you?’ It is becoming more common practice to ask this,” said Dr. Welles, who was not involved with the U.K. research.

The U.K. study drew on unpublished data from the Room to Breathe survey conducted by Dr. Carroll’s group during 2008-2009 in Canada, the United Kingdom, Greece, Hungary, South Africa, and the Netherlands. Only 358 of 930 (38.5%) children were found to be well controlled according to current Global Initiative for Asthma symptom-control criteria.

The analysis also found a highly significant association (P < .0001) between Childhood Asthma Control Test (C-ACT) score and reported bullying/teasing, with bullied children having lower scores. C-ACT–defined controlled asthma scores of 20 or higher were significantly associated with a lower risk of bullying (OR, 0.46; 95% CI, 0.28-0.76; P = .001).

In other study findings, harassment was more common in children whose asthma was serious enough to entail activity restriction (OR, 1.74; 95% CI, 1.11-2.75; P = .010) and who described their asthma as “bad” (OR, 3.02; 95% CI, 1.86-4.85; P < .001), as well as those whose parents reported ongoing asthma-related health worries (OR, 1.64; 95% CI, 1.04-2.58; P = .024).

“When a child is clearly different from others, such as having bad asthma or being limited in activities due to asthma, they stand out more and are more frequently bullied,” said Tracy Evian Waasdorp, PhD, MSEd, director of research for school-based bullying and social-emotional learning at Children’s Hospital of Philadelphia, and also not a participant in the U.K. study.

In contrast to the 10% bullying rate in Dr. Carroll’s study, Dr. Waasdorp referred to a CHOP analysis of more than 64,000 youth from a Northeastern state in which those with asthma were 40% more likely to be victims of in-person bullying and 70% were more likely to be cyberbullied than youth without asthma. “Having a medical condition can therefore put you at risk of being bullied regardless of what country you live in,” she said.

CHOP policy encourages practitioners to routinely ask about bullying and to provide handouts and resources for parents, she added.

Interestingly, the U.K. investigators found that open public use of spacers was not associated with asthma-related bullying, nor was parental worry at diagnosis or parental concern about steroid use.

But according to Dr. Welles, “Kids may be using the inhaler in front of other kids, and they may be embarrassed and not want to be seen as different. So they may not use the inhaler when needed for gym class or sports, forcing them to sit out and then potentially be bullied again. It’s a vicious cycle.”

Previous research has identified the bullying and teasing of children with food allergies.

Behaviors have included allergy-specific harassment such as smearing peanut butter on a youngster’s forehead or putting peanut butter cookie crumbs in a child’s lunch box.

“In our survey we asked the question ‘Have you been teased or bullied because of your asthma?’ but we didn’t ask what form this took,” Dr. Carroll said. “But we were surprised at just how many children said yes. It’s time for more research, I think.”

“There are never enough studies around this,” added Dr. Welles. “Bullying, whether because of asthma or otherwise, has the potential for long-term effects well into adulthood.”

In the meantime, asthma consultations should incorporate specific questions about bullying. They should also be child focused in order to gain a representative appreciation of asthma control and its effect on the child’s life.

“As pediatricians, we need to be continuously supporting parents and find the help they need to address any mental health issues,” Dr. Welles said. “Every pediatrician and parent needs to be aware and recognize when something is different in their child’s life. Please don’t ignore it.”

Dr. Waasdorp stressed that school and other communities should be aware that children with asthma may be at increased risk for aggression and harmful interactions related to their asthma. “Programming to reduce bullying should focus broadly on shifting the climate so that bullying is not perceived to be normative and on improving ‘upstander,’ or positive bystander, responses.” she said.

The original survey was funded by Nycomed (Zurich). No additional funding was requested for the current analysis. Dr. Carroll reported personal fees from GlaxoSmithKline, Novartis, and Trudell Medical International outside the submitted work. Dr. Welles and Dr. Waasdorp disclosed no competing interests relevant to their comments.

The risk of bullying and teasing is higher in children and young people with poorer asthma control, an international study reported. Published online in the Archives of Disease in Childhood, the Room to Breathe survey of 943 children in six countries found 9.9% had experienced asthma-related bullying or teasing (n = 93).

Children with well-controlled disease, however, were less likely to report being victimized by asthma-related bullying/teasing: odds ratio, 0.51; 95% confidence interval, 0.23-0.84; P = .006).

“It’s important for pediatricians to recognize that children and young people with asthma commonly report bullying or teasing as a result of their condition,” Will Carroll, MD, of the Paediatric Respiratory Service at Staffordshire Children’s Hospital at Royal Stoke, Stoke-on-Trent, England, told this news organization. “Pediatricians should talk to children themselves with asthma about this and not just their parents, and efforts should be made to improve asthma control whenever possible.”

Though common and potentially long-lasting in its effects, bullying is rarely addressed by health care professionals, the U.K. authors said.

But things may differ in the United States. According to Mark Welles, MD, a pediatrician at Cohen Children’s Medical Center at Northwell Health in Queen’s, N.Y., and regional cochair of the American Academy of Pediatrics antibullying committee, young doctors here are trained to ask about bullying when seeing a child, no matter what the reason for the visit. “It’s important to build a rapport with the child, and you need to ask about the disease they may have but also generally ask, ‘How are things at school? Is everyone nice to you?’ It is becoming more common practice to ask this,” said Dr. Welles, who was not involved with the U.K. research.

The U.K. study drew on unpublished data from the Room to Breathe survey conducted by Dr. Carroll’s group during 2008-2009 in Canada, the United Kingdom, Greece, Hungary, South Africa, and the Netherlands. Only 358 of 930 (38.5%) children were found to be well controlled according to current Global Initiative for Asthma symptom-control criteria.

The analysis also found a highly significant association (P < .0001) between Childhood Asthma Control Test (C-ACT) score and reported bullying/teasing, with bullied children having lower scores. C-ACT–defined controlled asthma scores of 20 or higher were significantly associated with a lower risk of bullying (OR, 0.46; 95% CI, 0.28-0.76; P = .001).

In other study findings, harassment was more common in children whose asthma was serious enough to entail activity restriction (OR, 1.74; 95% CI, 1.11-2.75; P = .010) and who described their asthma as “bad” (OR, 3.02; 95% CI, 1.86-4.85; P < .001), as well as those whose parents reported ongoing asthma-related health worries (OR, 1.64; 95% CI, 1.04-2.58; P = .024).

“When a child is clearly different from others, such as having bad asthma or being limited in activities due to asthma, they stand out more and are more frequently bullied,” said Tracy Evian Waasdorp, PhD, MSEd, director of research for school-based bullying and social-emotional learning at Children’s Hospital of Philadelphia, and also not a participant in the U.K. study.

In contrast to the 10% bullying rate in Dr. Carroll’s study, Dr. Waasdorp referred to a CHOP analysis of more than 64,000 youth from a Northeastern state in which those with asthma were 40% more likely to be victims of in-person bullying and 70% were more likely to be cyberbullied than youth without asthma. “Having a medical condition can therefore put you at risk of being bullied regardless of what country you live in,” she said.

CHOP policy encourages practitioners to routinely ask about bullying and to provide handouts and resources for parents, she added.

Interestingly, the U.K. investigators found that open public use of spacers was not associated with asthma-related bullying, nor was parental worry at diagnosis or parental concern about steroid use.

But according to Dr. Welles, “Kids may be using the inhaler in front of other kids, and they may be embarrassed and not want to be seen as different. So they may not use the inhaler when needed for gym class or sports, forcing them to sit out and then potentially be bullied again. It’s a vicious cycle.”

Previous research has identified the bullying and teasing of children with food allergies.

Behaviors have included allergy-specific harassment such as smearing peanut butter on a youngster’s forehead or putting peanut butter cookie crumbs in a child’s lunch box.

“In our survey we asked the question ‘Have you been teased or bullied because of your asthma?’ but we didn’t ask what form this took,” Dr. Carroll said. “But we were surprised at just how many children said yes. It’s time for more research, I think.”

“There are never enough studies around this,” added Dr. Welles. “Bullying, whether because of asthma or otherwise, has the potential for long-term effects well into adulthood.”

In the meantime, asthma consultations should incorporate specific questions about bullying. They should also be child focused in order to gain a representative appreciation of asthma control and its effect on the child’s life.

“As pediatricians, we need to be continuously supporting parents and find the help they need to address any mental health issues,” Dr. Welles said. “Every pediatrician and parent needs to be aware and recognize when something is different in their child’s life. Please don’t ignore it.”

Dr. Waasdorp stressed that school and other communities should be aware that children with asthma may be at increased risk for aggression and harmful interactions related to their asthma. “Programming to reduce bullying should focus broadly on shifting the climate so that bullying is not perceived to be normative and on improving ‘upstander,’ or positive bystander, responses.” she said.

The original survey was funded by Nycomed (Zurich). No additional funding was requested for the current analysis. Dr. Carroll reported personal fees from GlaxoSmithKline, Novartis, and Trudell Medical International outside the submitted work. Dr. Welles and Dr. Waasdorp disclosed no competing interests relevant to their comments.

Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.

Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.

Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.

The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.

Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.

The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).

When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.

These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.

In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.

The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.

The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.

The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.

“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
 

Findings support value of vaccination for children with asthma

“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.

“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.

Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.

“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.

“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.

Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.

The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.

Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.

Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.

Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.

The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.

Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.

The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).

When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.

These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.

In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.

The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.

The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.

The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.

“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
 

Findings support value of vaccination for children with asthma

“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.

“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.

Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.

“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.

“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.

Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.

The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.

Children and adolescents with poorly controlled asthma were three to six times more likely to be hospitalized with COVID-19 infections, based on data from a national study of more than 750,000 children in Scotland.

Although the majority of COVID-19 cases in children have been mild, some children require hospitalization, wrote Ting Shi, PhD, of the University of Edinburgh (Scotland) and colleagues.

Vaccination policies to potentially reduce infection and hospitalization of children remain inconsistent, the researchers said. Identifying which school-age children would derive the greatest benefit from vaccination “could help to reduce the risk of infection and consequently the need for children to have time off school; and might also reduce the risk of spread of SARS-CoV-2 within schools and households,” but the potential benefits of vaccination for children with asthma in particular have not been well studied, they wrote.

The United Kingdom’s Joint Commission on Vaccination and Immunisation commissioned research on the rates of hospitalization among children with poorly controlled asthma. In a national incidence cohort study published in The Lancet Respiratory Medicine, the researchers reviewed data from all children aged 5-17 years in Scotland who were enrolled in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). The total number of children in the dataset was 752,867, and 63,463 (8.4%) of these had diagnosed asthma. Among the children with asthma, 4,339 (6.8%) had confirmed COVID-19 infections between March 1, 2020, and July 27, 2021. A total of 67 infected children were hospitalized. Of the 689,404 children without asthma, 40,231 (5.8%) had confirmed COVID-19 infections, and 382 (0.9%) of these children were hospitalized.

Overall, hospital admission rates for COVID-19 were significantly higher among children with asthma, compared to those without asthma (adjusted hazard ratio, 1.49), and the rates increased among children with poorly controlled asthma.

The researchers used previous hospital admission for asthma as a measure of uncontrolled asthma, and found that hospitalization was at least six times as likely for children with poorly controlled asthma, compared with those with no asthma (aHR, 6.40), although children with well-controlled asthma also had an increased risk of hospitalization, compared with those with no asthma (aHR, 1.36).

When the researchers used oral corticosteroid prescriptions as an indicator of uncontrolled asthma, the adjusted hazard ratios were 3.38, 3.53, 1.52, and 1.34 for children with prescribed corticosteroid courses of three or more, two, one, and none, respectively, compared with children with no asthma.

These hazard ratios remained significant after controlling for factors including age, sex, socioeconomic status, comorbidity, and previous hospital admission, the researchers wrote.

In an age-based analysis, results were similar for children aged 12-17 years, but in children aged 5-11 years, the hospitalization risk decreased for those with one course of corticosteroids and reached the highest rate for those with three or more courses, rather than two courses.

The study findings were limited by several factors including the relatively small numbers of COVID-19 hospitalizations, ICU admissions, and deaths in children with asthma, the researchers noted. Other limitations include potential changes in asthma control over the study period, and lack of data on certain confounders such as tobacco use, unsuitable housing, and ethnicity, they noted. However, the results were strengthened by the use of a large, national dataset, and access to electronic health records, they said.

The findings reflect data from previous studies suggesting increased risk of hospitalization for patients with respiratory illness who develop COVID-19 infections, the researchers wrote.

The results emphasize the importance of good asthma control to protect children from severe COVID-19, and careful monitoring of children with poorly controlled asthma who do become infected, they added.

“The findings from this linkage of multiple data sources have helped inform the prioritisation of school-aged children with poorly controlled asthma for vaccines,” they concluded.
 

Findings support value of vaccination for children with asthma

“Pediatricians see many children who suffer from asthma, and although one could assume that these children would have more serious consequences from contracting COVID-19, the current study examines a large database in a way not possible in the United States to address the severity question,” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The authors used prior hospitalization rate or two prescriptions for oral corticosteroids as markers of asthma severity prior to the onset of COVID-19 in Scotland, and they collected retrospective data for 16 months of the pandemic through July of 2021, showing a significant increase in hospitalization for those children,” she said. Dr. Boulter said she was not surprised by this finding, given the impact of COVID-19 on the respiratory system.

“Pediatricians have found significant challenges from some groups of parents when discussing the indications and need for vaccination in their patients,” said Dr. Boulter. “Having this data on the increased risk of morbidity and mortality in children with asthma might help parents who are uncertain about the risk/benefit ratio of the vaccine make their decision,” she said.

Dr. Boulter said she hoped that additional studies will yield ongoing information about hospitalization rates for COVID-19 not only about asthma, but also other diagnoses affecting children in the United States and worldwide.

“It would also be important to see a breakdown of ethnic factors and adverse childhood experiences and how they relate to hospitalization and death from COVID-19,” Dr. Boulter said.

“The results of this study are not surprising, as we have known for a long time that children with severe asthma are more susceptible to severe respiratory viruses,” Francis E. Rushton, MD, a pediatrician in Beaufort, S.C., said in an interview. “But the study is still important, as it helps us determine which children are most urgently in need of protection from COVID-19 in any of its forms,” he emphasized. In particular, the current study underlines the importance of vaccinating children with unstable asthma, Dr. Rushton said.

Going forward, “it would be interesting to do additional studies looking at other markers for poor asthma control that could guide our vaccine efforts so that they are focused on those most at risk,” he added.

The study was supported by the UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and the Scottish Government. Lead author Dr. Shi had no financial conflicts to disclose. Dr. Rushton and Dr. Boulter had no financial conflicts to disclose, but each serves on the Editorial Advisory Board of Pediatric News.

Asthma highlights from ACAAI 2021 range from efficacy of biologic therapies to the late effects of COVID-19 in asthma patients, as reported by Dr Sandhya Khurana from the University of Rochester, in Rochester, New York.   

Dr Khurana opens by discussing a study that examined real-world data to assess the effect of COVID-19 infection in asthma patients. The study found that when adjusting for age, sex, BMI, use of inhaled corticosteroids, and atopy, Latino patients, when compared with non-Latino White and Black patients, were more susceptible to prolonged respiratory inflammation after COVID-19 infection.   

She then reports on a study that examined potential long-term morbidities associated with systemic corticosteroid (SCS) therapy. The study, which drew from a large administrative claims database, found that high-risk SCS exposure was associated with lifelong adverse chronic health conditions, including type 2 diabetes, hypertension, osteoporosis, and depression. Children ages 4-11 are particularly at risk.  

Next, Dr Khurana highlights studies evaluating the efficacy of dupilumab and tezepelumab, two novel biologics, in asthma patients who also have allergies. Both studies demonstrated a potential benefit for a broad population of patients with severe, uncontrolled asthma.   

Finally, Dr Khurana comments on ZEPHYR 2, a retrospective cohort study that looked to quantify the real-world impact of switching between biologics.  

--

Sandhya Khurana, MD, Professor, Department of Medicine, University of Rochester; Director, Mary Parkes Center for Asthma, Allergy & Pulmonary Care, Rochester, New York 

Sandhya Khurana, MD, has disclosed the following relevant financial relationships: 
Received research grant from: GlaxoSmithKline 

Asthma highlights from ACAAI 2021 range from efficacy of biologic therapies to the late effects of COVID-19 in asthma patients, as reported by Dr Sandhya Khurana from the University of Rochester, in Rochester, New York.   

Dr Khurana opens by discussing a study that examined real-world data to assess the effect of COVID-19 infection in asthma patients. The study found that when adjusting for age, sex, BMI, use of inhaled corticosteroids, and atopy, Latino patients, when compared with non-Latino White and Black patients, were more susceptible to prolonged respiratory inflammation after COVID-19 infection.   

She then reports on a study that examined potential long-term morbidities associated with systemic corticosteroid (SCS) therapy. The study, which drew from a large administrative claims database, found that high-risk SCS exposure was associated with lifelong adverse chronic health conditions, including type 2 diabetes, hypertension, osteoporosis, and depression. Children ages 4-11 are particularly at risk.  

Next, Dr Khurana highlights studies evaluating the efficacy of dupilumab and tezepelumab, two novel biologics, in asthma patients who also have allergies. Both studies demonstrated a potential benefit for a broad population of patients with severe, uncontrolled asthma.   

Finally, Dr Khurana comments on ZEPHYR 2, a retrospective cohort study that looked to quantify the real-world impact of switching between biologics.  

--

Sandhya Khurana, MD, Professor, Department of Medicine, University of Rochester; Director, Mary Parkes Center for Asthma, Allergy & Pulmonary Care, Rochester, New York 

Sandhya Khurana, MD, has disclosed the following relevant financial relationships: 
Received research grant from: GlaxoSmithKline 

Asthma highlights from ACAAI 2021 range from efficacy of biologic therapies to the late effects of COVID-19 in asthma patients, as reported by Dr Sandhya Khurana from the University of Rochester, in Rochester, New York.   

Dr Khurana opens by discussing a study that examined real-world data to assess the effect of COVID-19 infection in asthma patients. The study found that when adjusting for age, sex, BMI, use of inhaled corticosteroids, and atopy, Latino patients, when compared with non-Latino White and Black patients, were more susceptible to prolonged respiratory inflammation after COVID-19 infection.   

She then reports on a study that examined potential long-term morbidities associated with systemic corticosteroid (SCS) therapy. The study, which drew from a large administrative claims database, found that high-risk SCS exposure was associated with lifelong adverse chronic health conditions, including type 2 diabetes, hypertension, osteoporosis, and depression. Children ages 4-11 are particularly at risk.  

Next, Dr Khurana highlights studies evaluating the efficacy of dupilumab and tezepelumab, two novel biologics, in asthma patients who also have allergies. Both studies demonstrated a potential benefit for a broad population of patients with severe, uncontrolled asthma.   

Finally, Dr Khurana comments on ZEPHYR 2, a retrospective cohort study that looked to quantify the real-world impact of switching between biologics.  

--

Sandhya Khurana, MD, Professor, Department of Medicine, University of Rochester; Director, Mary Parkes Center for Asthma, Allergy & Pulmonary Care, Rochester, New York 

Sandhya Khurana, MD, has disclosed the following relevant financial relationships: 
Received research grant from: GlaxoSmithKline 

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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