Immunology

For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.

A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.

An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.

Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”

Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.

Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
 

Concerns about SLIT

One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.

On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.

But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).

Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.

Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”

Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.

But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.

Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”

On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”

Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.

SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.

As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.

One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.

A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.

For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.

A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.

An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.

Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”

Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.

Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
 

Concerns about SLIT

One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.

On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.

But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).

Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.

Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”

Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.

But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.

Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”

On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”

Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.

SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.

As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.

One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.

A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.

For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.

A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.

An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.

Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”

Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.

Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
 

Concerns about SLIT

One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.

On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.

But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).

Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.

Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”

Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.

But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.

Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”

On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”

Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.

SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.

As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.

One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.

A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.

Some days it feels like more than half of the journal articles I encounter report data suggesting that poverty is associated with some disease entity. I realize that young postgraduates are under some pressure to publish, but I’m ready for a break. I and most pediatricians already know, or at least have assumed, that in general and with few exceptions unwellness and poverty are closely linked. Whether that association is causal or not is a more interesting question. The answer, I suspect, depends on which health condition we are talking about. For the moment I think we should assume that poverty is more likely a major contributor and not merely a fellow traveler of poor health.

Some other questions: What are we as pediatricians expected to do about poverty? Is awareness sufficient? Should I be content with having an elevated awareness that a certain patient has a given disease because I know his family is economically challenged? Or, conversely, should I be satisfied that I have asked about a family’s economic distress when I have just diagnosed a child with asthma? The answer to those questions is a very personal one for each of us to ponder and may depend on where we feel we can best invest our time and skill set.

Like me, you may feel that the focus of your professional life is better spent diagnosing and treating the collateral damage of poverty and addressing economic inequities in your philanthropic activities and your choices at the polls. On the other hand, you may choose to use your public persona as a physician to more actively address poverty whether it is on a local, national, or global stage. There is no correct answer and a hybrid may work best for you.

On the other hand, while you agree that there is some link between poverty and unwellness, perhaps the issue is overblown and we should pay more attention to other factors such as the sad state of the family in both disadvantaged and advantaged populations. Maybe if we worked harder to foster and support two-parent families the drag of economic disadvantage would be reduced.

I recently encountered a study that explores this very question. Christina Cross, PhD, a postdoctoral fellow in the department of sociology at Harvard University, reports on her soon-to-be-published study of a nationally representative sample in which she found that, using a selection of academic metrics including earned grades, likelihood of grade repetition, and rates of suspension, in low-income families there was no difference in achievement between Black youth raised in single-parent households and Black youth raised in two-parent households. However, in well-off families, Black youth raised in two-parent households had better academic metrics. (“Why living in a two-parent home isn’t a cure-all for Black students.” Christina Cross. The Harvard Gazette. 2021 Jun 3).

I guess few of us are surprised that living in a two-parent household can provide a child with some advantages. However, it is disappointing and again not surprising that poverty can rob a child of these advantages. While it may make us feel like we are doing something when we offer counseling that promotes two-family households, this may be no more valuable than supporting apple pie and motherhood. Dr. Cross concludes that President Biden’s proposed American Families Plan is more likely to succeed than those focused on counseling because it will offer direct financial support with its tax credits and subsidies.*

Let’s hope she is correct.

* This story was updated on July 6, 2021. 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Some days it feels like more than half of the journal articles I encounter report data suggesting that poverty is associated with some disease entity. I realize that young postgraduates are under some pressure to publish, but I’m ready for a break. I and most pediatricians already know, or at least have assumed, that in general and with few exceptions unwellness and poverty are closely linked. Whether that association is causal or not is a more interesting question. The answer, I suspect, depends on which health condition we are talking about. For the moment I think we should assume that poverty is more likely a major contributor and not merely a fellow traveler of poor health.

Some other questions: What are we as pediatricians expected to do about poverty? Is awareness sufficient? Should I be content with having an elevated awareness that a certain patient has a given disease because I know his family is economically challenged? Or, conversely, should I be satisfied that I have asked about a family’s economic distress when I have just diagnosed a child with asthma? The answer to those questions is a very personal one for each of us to ponder and may depend on where we feel we can best invest our time and skill set.

Like me, you may feel that the focus of your professional life is better spent diagnosing and treating the collateral damage of poverty and addressing economic inequities in your philanthropic activities and your choices at the polls. On the other hand, you may choose to use your public persona as a physician to more actively address poverty whether it is on a local, national, or global stage. There is no correct answer and a hybrid may work best for you.

On the other hand, while you agree that there is some link between poverty and unwellness, perhaps the issue is overblown and we should pay more attention to other factors such as the sad state of the family in both disadvantaged and advantaged populations. Maybe if we worked harder to foster and support two-parent families the drag of economic disadvantage would be reduced.

I recently encountered a study that explores this very question. Christina Cross, PhD, a postdoctoral fellow in the department of sociology at Harvard University, reports on her soon-to-be-published study of a nationally representative sample in which she found that, using a selection of academic metrics including earned grades, likelihood of grade repetition, and rates of suspension, in low-income families there was no difference in achievement between Black youth raised in single-parent households and Black youth raised in two-parent households. However, in well-off families, Black youth raised in two-parent households had better academic metrics. (“Why living in a two-parent home isn’t a cure-all for Black students.” Christina Cross. The Harvard Gazette. 2021 Jun 3).

I guess few of us are surprised that living in a two-parent household can provide a child with some advantages. However, it is disappointing and again not surprising that poverty can rob a child of these advantages. While it may make us feel like we are doing something when we offer counseling that promotes two-family households, this may be no more valuable than supporting apple pie and motherhood. Dr. Cross concludes that President Biden’s proposed American Families Plan is more likely to succeed than those focused on counseling because it will offer direct financial support with its tax credits and subsidies.*

Let’s hope she is correct.

* This story was updated on July 6, 2021. 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Some days it feels like more than half of the journal articles I encounter report data suggesting that poverty is associated with some disease entity. I realize that young postgraduates are under some pressure to publish, but I’m ready for a break. I and most pediatricians already know, or at least have assumed, that in general and with few exceptions unwellness and poverty are closely linked. Whether that association is causal or not is a more interesting question. The answer, I suspect, depends on which health condition we are talking about. For the moment I think we should assume that poverty is more likely a major contributor and not merely a fellow traveler of poor health.

Some other questions: What are we as pediatricians expected to do about poverty? Is awareness sufficient? Should I be content with having an elevated awareness that a certain patient has a given disease because I know his family is economically challenged? Or, conversely, should I be satisfied that I have asked about a family’s economic distress when I have just diagnosed a child with asthma? The answer to those questions is a very personal one for each of us to ponder and may depend on where we feel we can best invest our time and skill set.

Like me, you may feel that the focus of your professional life is better spent diagnosing and treating the collateral damage of poverty and addressing economic inequities in your philanthropic activities and your choices at the polls. On the other hand, you may choose to use your public persona as a physician to more actively address poverty whether it is on a local, national, or global stage. There is no correct answer and a hybrid may work best for you.

On the other hand, while you agree that there is some link between poverty and unwellness, perhaps the issue is overblown and we should pay more attention to other factors such as the sad state of the family in both disadvantaged and advantaged populations. Maybe if we worked harder to foster and support two-parent families the drag of economic disadvantage would be reduced.

I recently encountered a study that explores this very question. Christina Cross, PhD, a postdoctoral fellow in the department of sociology at Harvard University, reports on her soon-to-be-published study of a nationally representative sample in which she found that, using a selection of academic metrics including earned grades, likelihood of grade repetition, and rates of suspension, in low-income families there was no difference in achievement between Black youth raised in single-parent households and Black youth raised in two-parent households. However, in well-off families, Black youth raised in two-parent households had better academic metrics. (“Why living in a two-parent home isn’t a cure-all for Black students.” Christina Cross. The Harvard Gazette. 2021 Jun 3).

I guess few of us are surprised that living in a two-parent household can provide a child with some advantages. However, it is disappointing and again not surprising that poverty can rob a child of these advantages. While it may make us feel like we are doing something when we offer counseling that promotes two-family households, this may be no more valuable than supporting apple pie and motherhood. Dr. Cross concludes that President Biden’s proposed American Families Plan is more likely to succeed than those focused on counseling because it will offer direct financial support with its tax credits and subsidies.*

Let’s hope she is correct.

* This story was updated on July 6, 2021. 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

The Food and Drug Administration has approved one formulation of azelastine (Astepro) nasal spray for nonprescription treatment of allergies, making it the first nasal antihistamine available over the counter in the United States.

The 0.15% strength of azelastine hydrochloride nasal spray is now approved for nonprescription treatment of seasonal and perennial allergic rhinitis in adults and children 6 years of age or older, the agency said. The 0.1% strength remains a prescription product that is indicated in younger children.

The “approval provides individuals an option for a safe and effective nasal antihistamine without requiring the assistance of a health care provider,” Theresa M. Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said in a prepared statement.

The FDA granted the nonprescription approval to Bayer Healthcare LLC, which said in a press release that the nasal spray would be available in national mass retail locations starting in the first quarter of 2022.

Oral antihistamines such as cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra) have been on store shelves for years. Azelastine 0.15% will be the first and only over-the-counter antihistamine for indoor and outdoor allergy relief in a nasal formulation, Bayer said.

An over-the-counter nasal antihistamine could be a better option for some allergy sufferers when compared with what is already over the counter, said Tracy Prematta, MD, a private practice allergist in Havertown, Pa.

“In general, I like the nasal antihistamines,” Dr. Prematta said in an interview. “They work quickly, whereas the nasal steroids don’t, and I think a lot of people who go to the drugstore looking for allergy relief are actually looking for something quick-acting.”

However, the cost of the over-the-counter azelastine may play a big role in whether patients go with the prescription or nonprescription option, according to Dr. Prematta.

Bayer has not yet set the price for nonprescription azelastine, a company spokesperson told this news organization.

The change in azelastine approval status happened through a regulatory process called an Rx-to-OTC switch. According to the FDA, products switched to nonprescription status need to have data demonstrating that they are safe and effective as self-medication when used as directed.

The product manufacturer has to show that consumers know how to use the drug safely and effectively without a health care professional supervising them, the FDA said.

The FDA considers the change in status for azelastine a partial Rx-to-OTC switch, since the 0.15% strength is now over the counter and the 0.1% strength remains a prescription product.

The 0.1% strength is indicated for perennial allergies in children 6 months to 6 years old, and seasonal allergies for children 2-6 years old, according to the FDA.

Drowsiness is a side effect of azelastine, the FDA said. According to prescribing information, consumers using the nasal spray need to be careful when driving or operating machinery, and should avoid alcohol.

Using the product with alcohol, sedatives, or tranquilizers may increase drowsiness, the agency added.

Sedation is also common with the oral antihistamines people take to treat their allergies, said Dr. Prematta, who added that patients may also complain of dry mouth, nose, or throat.

Although some allergy sufferers dislike the taste of antihistamine nasal spray, they can try to overcome that issue by tilting the head forward, pointing the tip of the nozzle toward the outside of the nose, and sniffing gently, Dr. Prematta said.

“That really minimizes what gets in the back of your throat, so taste becomes less of a problem,” she explained.

Dr. Prematta has disclosed no relevant financial relationships.
 

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

The Food and Drug Administration has approved one formulation of azelastine (Astepro) nasal spray for nonprescription treatment of allergies, making it the first nasal antihistamine available over the counter in the United States.

The 0.15% strength of azelastine hydrochloride nasal spray is now approved for nonprescription treatment of seasonal and perennial allergic rhinitis in adults and children 6 years of age or older, the agency said. The 0.1% strength remains a prescription product that is indicated in younger children.

The “approval provides individuals an option for a safe and effective nasal antihistamine without requiring the assistance of a health care provider,” Theresa M. Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said in a prepared statement.

The FDA granted the nonprescription approval to Bayer Healthcare LLC, which said in a press release that the nasal spray would be available in national mass retail locations starting in the first quarter of 2022.

Oral antihistamines such as cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra) have been on store shelves for years. Azelastine 0.15% will be the first and only over-the-counter antihistamine for indoor and outdoor allergy relief in a nasal formulation, Bayer said.

An over-the-counter nasal antihistamine could be a better option for some allergy sufferers when compared with what is already over the counter, said Tracy Prematta, MD, a private practice allergist in Havertown, Pa.

“In general, I like the nasal antihistamines,” Dr. Prematta said in an interview. “They work quickly, whereas the nasal steroids don’t, and I think a lot of people who go to the drugstore looking for allergy relief are actually looking for something quick-acting.”

However, the cost of the over-the-counter azelastine may play a big role in whether patients go with the prescription or nonprescription option, according to Dr. Prematta.

Bayer has not yet set the price for nonprescription azelastine, a company spokesperson told this news organization.

The change in azelastine approval status happened through a regulatory process called an Rx-to-OTC switch. According to the FDA, products switched to nonprescription status need to have data demonstrating that they are safe and effective as self-medication when used as directed.

The product manufacturer has to show that consumers know how to use the drug safely and effectively without a health care professional supervising them, the FDA said.

The FDA considers the change in status for azelastine a partial Rx-to-OTC switch, since the 0.15% strength is now over the counter and the 0.1% strength remains a prescription product.

The 0.1% strength is indicated for perennial allergies in children 6 months to 6 years old, and seasonal allergies for children 2-6 years old, according to the FDA.

Drowsiness is a side effect of azelastine, the FDA said. According to prescribing information, consumers using the nasal spray need to be careful when driving or operating machinery, and should avoid alcohol.

Using the product with alcohol, sedatives, or tranquilizers may increase drowsiness, the agency added.

Sedation is also common with the oral antihistamines people take to treat their allergies, said Dr. Prematta, who added that patients may also complain of dry mouth, nose, or throat.

Although some allergy sufferers dislike the taste of antihistamine nasal spray, they can try to overcome that issue by tilting the head forward, pointing the tip of the nozzle toward the outside of the nose, and sniffing gently, Dr. Prematta said.

“That really minimizes what gets in the back of your throat, so taste becomes less of a problem,” she explained.

Dr. Prematta has disclosed no relevant financial relationships.
 

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

The Food and Drug Administration has approved one formulation of azelastine (Astepro) nasal spray for nonprescription treatment of allergies, making it the first nasal antihistamine available over the counter in the United States.

The 0.15% strength of azelastine hydrochloride nasal spray is now approved for nonprescription treatment of seasonal and perennial allergic rhinitis in adults and children 6 years of age or older, the agency said. The 0.1% strength remains a prescription product that is indicated in younger children.

The “approval provides individuals an option for a safe and effective nasal antihistamine without requiring the assistance of a health care provider,” Theresa M. Michele, MD, director of the office of nonprescription drugs in the FDA’s Center for Drug Evaluation and Research, said in a prepared statement.

The FDA granted the nonprescription approval to Bayer Healthcare LLC, which said in a press release that the nasal spray would be available in national mass retail locations starting in the first quarter of 2022.

Oral antihistamines such as cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra) have been on store shelves for years. Azelastine 0.15% will be the first and only over-the-counter antihistamine for indoor and outdoor allergy relief in a nasal formulation, Bayer said.

An over-the-counter nasal antihistamine could be a better option for some allergy sufferers when compared with what is already over the counter, said Tracy Prematta, MD, a private practice allergist in Havertown, Pa.

“In general, I like the nasal antihistamines,” Dr. Prematta said in an interview. “They work quickly, whereas the nasal steroids don’t, and I think a lot of people who go to the drugstore looking for allergy relief are actually looking for something quick-acting.”

However, the cost of the over-the-counter azelastine may play a big role in whether patients go with the prescription or nonprescription option, according to Dr. Prematta.

Bayer has not yet set the price for nonprescription azelastine, a company spokesperson told this news organization.

The change in azelastine approval status happened through a regulatory process called an Rx-to-OTC switch. According to the FDA, products switched to nonprescription status need to have data demonstrating that they are safe and effective as self-medication when used as directed.

The product manufacturer has to show that consumers know how to use the drug safely and effectively without a health care professional supervising them, the FDA said.

The FDA considers the change in status for azelastine a partial Rx-to-OTC switch, since the 0.15% strength is now over the counter and the 0.1% strength remains a prescription product.

The 0.1% strength is indicated for perennial allergies in children 6 months to 6 years old, and seasonal allergies for children 2-6 years old, according to the FDA.

Drowsiness is a side effect of azelastine, the FDA said. According to prescribing information, consumers using the nasal spray need to be careful when driving or operating machinery, and should avoid alcohol.

Using the product with alcohol, sedatives, or tranquilizers may increase drowsiness, the agency added.

Sedation is also common with the oral antihistamines people take to treat their allergies, said Dr. Prematta, who added that patients may also complain of dry mouth, nose, or throat.

Although some allergy sufferers dislike the taste of antihistamine nasal spray, they can try to overcome that issue by tilting the head forward, pointing the tip of the nozzle toward the outside of the nose, and sniffing gently, Dr. Prematta said.

“That really minimizes what gets in the back of your throat, so taste becomes less of a problem,” she explained.

Dr. Prematta has disclosed no relevant financial relationships.
 

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

Allergic conjunctivitis harms quality of life for children and their parents, apparently causing greater day-to-day worries than potentially blinding diseases, researchers report.

Parents worry especially that treatments might not be effective, according to Shi-yao Zhang, MD, and colleagues from Sun Yat-sen University, Guangzhou, China. “This finding suggests that more communication with parents regarding treatment and prognosis is needed,” they write in an article published online June 10 in JAMA Ophthalmology.

One of the most prevalent eye disorders in children, allergic conjunctivitis is often chronic, leading patients to ask repeatedly for help from physicians. It can take an emotional toll and can cause children to miss school.

“With any sign of a slightly pink eye [or a] runny nose, which are very common with allergies, children are being sent home, because everyone’s concerned about COVID,” said Yi Ning J. Strube, MD, an associate professor of ophthalmology and pediatrics at Queen’s University, Kingston, Canada, whose commentary appears in the same issue of JAMA Ophthalmology.

Adolescents are also sometimes accused of smoking cannabis because of their red eyes, she said.

However, little research has examined the effects of allergic conjunctivitis on the quality of life of children and their guardians, Dr. Zhang and colleagues write. To fill that gap, the researchers administered the Pediatric Quality of Life Inventory (PedsQL) to 92 children with allergic conjunctivitis and their parents. The children were aged 5 to 18 years.

The researchers administered the same questionnaire to 96 healthy children of the same ages, along with their parents. These participants served as a control group.

On a scale of 0 to 100, in which a higher score signifies a better quality of life, the median total PedsQL score was 69.6 for children with allergic conjunctivitis versus 96.7 for the control group.

Subscores of physical, emotional, social, and especially school functioning were all significantly lower for the children with allergic conjunctivitis than for the control persons. “Because children generally spend most of their time in the school environment, this outcome raises an issue regarding whether children have a poorer performance in their education,” Dr. Zhang and colleagues write.

Dr. Strube recommends that physicians educate their patients about allergic conjunctivitis using handouts or high-quality websites. She often refers patients and their families to the allergic conjunctivitis webpage of the American Academy of Pediatric Ophthalmology and Strabismus.

She tells parents to have their child “take a shower and wash their hair when they get home before they rub their pollen-filled hair on their pillowcase and make their allergy symptoms worse.”

Parents and schools should try to filter pollen and other allergens from indoor air, she added.

Parents of the children with allergic conjunctivitis in the study also reported lower quality of life; they scored 68.8, versus 96.5 for parents of children in the control group. The differences for both parents and children were statistically significant (P < .001). Overall, the parents’ quality-of-life scores correlated with their children’s (correlation coefficient, r = 0.59; P < .001).

Children with vernal or atopic keratoconjunctivitis scored 3.3 points lower on health-related quality of life than those with seasonal allergic conjunctivitis.

Children with higher corneal fluorescein staining scores also had lower quality-of-life scores. Parents whose children had higher corneal fluorescein staining scores and also those who had multiple consultations with health care practitioners also reported lower quality of life.

The quality-of-life scores of the children with allergic conjunctivitis were lower than scores in previous studies for children with vision-threatening diseases, such as glaucoma and congenital cataract. This may be because glaucoma and cataracts do not typically cause discomfort even if they impair the patient’s vision, said Dr. Strube.

She pointed out one potential flaw in the study: In the cohort with allergic conjunctivitis, 83.7% were boys, compared to 42.7% of the control group. Vernal keratoconjunctivitis affects more boys than girls, and not controlling for this factor could have confounded the data, Dr. Strube said.

It could also be useful to replicate the study in other countries to see whether geographic or cultural factors affected the results, she said. “A lot of these big centers around the world, including in China, have poor air quality, so that may be contributing to patients’ symptoms,” she said. “With regards to reported health quality of life and impact on education, results from different parts of the world may be different, due to parenting styles and education styles,” she said.

The study was supported by the National Natural Science Foundation of China and the Science Foundation of Guangdong Province. Dr. Zhang and colleagues reported no relevant financial relationships. Dr. Strube reported receiving personal fees from Santen Canada Advisory Board Consultant outside the submitted work.

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

Allergic conjunctivitis harms quality of life for children and their parents, apparently causing greater day-to-day worries than potentially blinding diseases, researchers report.

Parents worry especially that treatments might not be effective, according to Shi-yao Zhang, MD, and colleagues from Sun Yat-sen University, Guangzhou, China. “This finding suggests that more communication with parents regarding treatment and prognosis is needed,” they write in an article published online June 10 in JAMA Ophthalmology.

One of the most prevalent eye disorders in children, allergic conjunctivitis is often chronic, leading patients to ask repeatedly for help from physicians. It can take an emotional toll and can cause children to miss school.

“With any sign of a slightly pink eye [or a] runny nose, which are very common with allergies, children are being sent home, because everyone’s concerned about COVID,” said Yi Ning J. Strube, MD, an associate professor of ophthalmology and pediatrics at Queen’s University, Kingston, Canada, whose commentary appears in the same issue of JAMA Ophthalmology.

Adolescents are also sometimes accused of smoking cannabis because of their red eyes, she said.

However, little research has examined the effects of allergic conjunctivitis on the quality of life of children and their guardians, Dr. Zhang and colleagues write. To fill that gap, the researchers administered the Pediatric Quality of Life Inventory (PedsQL) to 92 children with allergic conjunctivitis and their parents. The children were aged 5 to 18 years.

The researchers administered the same questionnaire to 96 healthy children of the same ages, along with their parents. These participants served as a control group.

On a scale of 0 to 100, in which a higher score signifies a better quality of life, the median total PedsQL score was 69.6 for children with allergic conjunctivitis versus 96.7 for the control group.

Subscores of physical, emotional, social, and especially school functioning were all significantly lower for the children with allergic conjunctivitis than for the control persons. “Because children generally spend most of their time in the school environment, this outcome raises an issue regarding whether children have a poorer performance in their education,” Dr. Zhang and colleagues write.

Dr. Strube recommends that physicians educate their patients about allergic conjunctivitis using handouts or high-quality websites. She often refers patients and their families to the allergic conjunctivitis webpage of the American Academy of Pediatric Ophthalmology and Strabismus.

She tells parents to have their child “take a shower and wash their hair when they get home before they rub their pollen-filled hair on their pillowcase and make their allergy symptoms worse.”

Parents and schools should try to filter pollen and other allergens from indoor air, she added.

Parents of the children with allergic conjunctivitis in the study also reported lower quality of life; they scored 68.8, versus 96.5 for parents of children in the control group. The differences for both parents and children were statistically significant (P < .001). Overall, the parents’ quality-of-life scores correlated with their children’s (correlation coefficient, r = 0.59; P < .001).

Children with vernal or atopic keratoconjunctivitis scored 3.3 points lower on health-related quality of life than those with seasonal allergic conjunctivitis.

Children with higher corneal fluorescein staining scores also had lower quality-of-life scores. Parents whose children had higher corneal fluorescein staining scores and also those who had multiple consultations with health care practitioners also reported lower quality of life.

The quality-of-life scores of the children with allergic conjunctivitis were lower than scores in previous studies for children with vision-threatening diseases, such as glaucoma and congenital cataract. This may be because glaucoma and cataracts do not typically cause discomfort even if they impair the patient’s vision, said Dr. Strube.

She pointed out one potential flaw in the study: In the cohort with allergic conjunctivitis, 83.7% were boys, compared to 42.7% of the control group. Vernal keratoconjunctivitis affects more boys than girls, and not controlling for this factor could have confounded the data, Dr. Strube said.

It could also be useful to replicate the study in other countries to see whether geographic or cultural factors affected the results, she said. “A lot of these big centers around the world, including in China, have poor air quality, so that may be contributing to patients’ symptoms,” she said. “With regards to reported health quality of life and impact on education, results from different parts of the world may be different, due to parenting styles and education styles,” she said.

The study was supported by the National Natural Science Foundation of China and the Science Foundation of Guangdong Province. Dr. Zhang and colleagues reported no relevant financial relationships. Dr. Strube reported receiving personal fees from Santen Canada Advisory Board Consultant outside the submitted work.

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

Allergic conjunctivitis harms quality of life for children and their parents, apparently causing greater day-to-day worries than potentially blinding diseases, researchers report.

Parents worry especially that treatments might not be effective, according to Shi-yao Zhang, MD, and colleagues from Sun Yat-sen University, Guangzhou, China. “This finding suggests that more communication with parents regarding treatment and prognosis is needed,” they write in an article published online June 10 in JAMA Ophthalmology.

One of the most prevalent eye disorders in children, allergic conjunctivitis is often chronic, leading patients to ask repeatedly for help from physicians. It can take an emotional toll and can cause children to miss school.

“With any sign of a slightly pink eye [or a] runny nose, which are very common with allergies, children are being sent home, because everyone’s concerned about COVID,” said Yi Ning J. Strube, MD, an associate professor of ophthalmology and pediatrics at Queen’s University, Kingston, Canada, whose commentary appears in the same issue of JAMA Ophthalmology.

Adolescents are also sometimes accused of smoking cannabis because of their red eyes, she said.

However, little research has examined the effects of allergic conjunctivitis on the quality of life of children and their guardians, Dr. Zhang and colleagues write. To fill that gap, the researchers administered the Pediatric Quality of Life Inventory (PedsQL) to 92 children with allergic conjunctivitis and their parents. The children were aged 5 to 18 years.

The researchers administered the same questionnaire to 96 healthy children of the same ages, along with their parents. These participants served as a control group.

On a scale of 0 to 100, in which a higher score signifies a better quality of life, the median total PedsQL score was 69.6 for children with allergic conjunctivitis versus 96.7 for the control group.

Subscores of physical, emotional, social, and especially school functioning were all significantly lower for the children with allergic conjunctivitis than for the control persons. “Because children generally spend most of their time in the school environment, this outcome raises an issue regarding whether children have a poorer performance in their education,” Dr. Zhang and colleagues write.

Dr. Strube recommends that physicians educate their patients about allergic conjunctivitis using handouts or high-quality websites. She often refers patients and their families to the allergic conjunctivitis webpage of the American Academy of Pediatric Ophthalmology and Strabismus.

She tells parents to have their child “take a shower and wash their hair when they get home before they rub their pollen-filled hair on their pillowcase and make their allergy symptoms worse.”

Parents and schools should try to filter pollen and other allergens from indoor air, she added.

Parents of the children with allergic conjunctivitis in the study also reported lower quality of life; they scored 68.8, versus 96.5 for parents of children in the control group. The differences for both parents and children were statistically significant (P < .001). Overall, the parents’ quality-of-life scores correlated with their children’s (correlation coefficient, r = 0.59; P < .001).

Children with vernal or atopic keratoconjunctivitis scored 3.3 points lower on health-related quality of life than those with seasonal allergic conjunctivitis.

Children with higher corneal fluorescein staining scores also had lower quality-of-life scores. Parents whose children had higher corneal fluorescein staining scores and also those who had multiple consultations with health care practitioners also reported lower quality of life.

The quality-of-life scores of the children with allergic conjunctivitis were lower than scores in previous studies for children with vision-threatening diseases, such as glaucoma and congenital cataract. This may be because glaucoma and cataracts do not typically cause discomfort even if they impair the patient’s vision, said Dr. Strube.

She pointed out one potential flaw in the study: In the cohort with allergic conjunctivitis, 83.7% were boys, compared to 42.7% of the control group. Vernal keratoconjunctivitis affects more boys than girls, and not controlling for this factor could have confounded the data, Dr. Strube said.

It could also be useful to replicate the study in other countries to see whether geographic or cultural factors affected the results, she said. “A lot of these big centers around the world, including in China, have poor air quality, so that may be contributing to patients’ symptoms,” she said. “With regards to reported health quality of life and impact on education, results from different parts of the world may be different, due to parenting styles and education styles,” she said.

The study was supported by the National Natural Science Foundation of China and the Science Foundation of Guangdong Province. Dr. Zhang and colleagues reported no relevant financial relationships. Dr. Strube reported receiving personal fees from Santen Canada Advisory Board Consultant outside the submitted work.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

In the absence of formal clinical trials, pediatricians are racing to determine the efficacy and risks of currently used therapies for the SARS-CoV-2–linked multisystem inflammatory syndrome in children (MIS-C).

That requires rapid pragmatic evaluation of therapies. Two real-world observational studies published online June 16 in The New England Journal of Medicine do that, with differing results.

In the Overcoming COVID-19 study, investigators assessed initial therapy and outcomes for patients with MIS-C using surveillance data from 58 pediatric hospitals nationwide.

The results suggest that patients with MIS-C who were younger than 21 years of age and who were initially treated with intravenous immunoglobulin (IVIG) plus glucocorticoids fared better in terms of cardiovascular function.

The study included 518 children (median age, 8.7 years) who were admitted to the hospital between March and October 2020 and who received at least one immunomodulatory therapy. In a propensity score–matched analysis, those given IVIG plus glucocorticoids (n = 103) had a lower risk for the primary outcome of cardiovascular dysfunction on or after day 2 than those given IVIG alone (n = 103), at 17% versus 31% (risk ratio, 0.56; 95% confidence interval, 0.34-0.94).

Risks for individual aspects of the study’s composite outcome were also lower with IVIG plus glucocorticoids. Left ventricular dysfunction occurred in 8% and 17%, respectively (RR, 0.46; 95% CI, 0.19-1.15). Shock requiring vasopressor use emerged in 13% and 24%, respectively (RR, 0.54; 95% CI, 0.29-1.00).

In addition, there were fewer cases in which adjunctive therapy was given on day one among those who received combination therapy than among those who received IVIG alone, at 34% versus 70% (RR, 0.49; 95% CI, 0.36-0.65), but the risk for fever was not lower on or after day two (31% and 40%, respectively; RR, 0.78; 95% CI, 0.53-1.13).

Lead author Mary Beth F. Son, MD, director of the rheumatology program at Boston Children’s Hospital, who is also associate professor of pediatrics at Harvard Medical School, stressed that the study did not assess which MIS-C patients should receive treatment. “Rather, we studied children who had been treated with one of two initial regimens and then assessed short-term outcomes,” she told this news organization.

Going forward, it will be important to study which children should receive immunomodulatory treatment, Dr. Son said. “Specifically, can the less ill children receive IVIG alone or no treatment? This is an unanswered question at the moment, which could be addressed with a randomized controlled trial.”

Future directions, she added, will include assessing long-term cardiac outcomes for patients with MIS-C as well as studying outpatient regimens, especially those that involve steroids.

Earlier this year, French investigators found better outcomes with combined corticosteroids and IVIG than with IVIG alone. They suggested that combination therapy should be the standard of care, given the present state of therapeutic knowledge.
 

Maybe not so standard

Different results emerged, however, from an international study of MIS-C that compared three, rather than two, treatment approaches. Collaborators from the Best Available Treatment Study for MIS-C (BATS) evaluated data for 614 children with suspected MIS-C between June 2020 and February 2021 in 32 countries and found no substantial differences in recovery among children whose primary treatment was IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone.

The study by Andrew J. McArdle, MB BChir, MSC, a clinical research fellow at Imperial College London, and colleagues was published June 16 in The New England Journal of Medicine.

In the BATS cohort, 246 received IVIG alone, 208 received IVIG plus glucocorticoids, and 99 received glucocorticoids alone. Twenty-two patients received other combinations, including biologics, and 39 received no immunomodulatory therapy.

Among patients who were included in the primary analysis, death occurred or inotropic or ventilatory support was employed in 56 of 180 of the patients who received IVIG plus glucocorticoids, compared with 44 of 211 patients treated with IVIG alone, for an adjusted odds ratio (aOR) of 0.77 (95% CI, 0.33-1.82). Among those who received glucocorticoids alone, 17 of 83 met the primary endpoint of death or inotropic or ventilatory support, for an aOR relative to IVIG alone of 0.54 (95% CI, 0.22-1.33).

After adjustments, the likelihood for reduced disease severity was similar in the two groups relative to IVIG alone, at 0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone. Time to reduction in disease severity was also comparable across all groups.

Some of the differences between the U.S. study and the global studies could be the result of the larger size of the international cohort and possibly a difference in the strains of virus in the United States and abroad, according to S. Sexson Tejtel, MD, PhD, MPH, a pediatric cardiologist at Texas Children’s Hospital and an assistant professor at Baylor College of Medicine, Houston, Texas. “Some strains make children sicker than others, and they’re going to need more treatment,” said Dr. Sexson Tejtel, who was not involved in either study.

Dr. Sexson Tejtel also noted that the U.S. researchers did not assess outcomes among children treated with steroids alone. “It would be interesting to know what steroids alone look like in the U.S. MIS-C population,” she said in an interview.

BATS corresponding author Michael Levin, MBE, PhD, FRCPCH, an Imperial College professor of pediatrics and international child health, told this news organization that the differing results may have arisen because of the international study’s three-treatment focus, its wider spectrum of patients, and its different endpoints: Death and inotropic support on or after day 2, versus echocardiographic left ventricular dysfunction or inotropic usage.

Regardless of the differences between the two studies, neither establishes the most effective single or combination treatment, writes Roberta L. DeBiasi, MD, of the Division of Pediatric Infectious Diseases at Children’s National Hospital and Research Institute and George Washington University, Washington, in an accompanying editorial. “Specifically, neither study was powered to include an evaluation of approaches that steer away from broad immunosuppression with glucocorticoids and that focus on more targeted and titratable treatments with biologic agents, such as anakinra and infliximab,” she writes.

Dr. DeBiasi adds that long-term follow-up studies of cardiac and noncardiac outcomes in these patients will launch soon. “Meanwhile, continued collaboration across centers is essential to decreasing the short-term incidence of death and complications,” she writes.

“It will be interesting as we apply results from these studies as they come out to see how they change our practice,” Dr. Sexson Tejtel said. “And it would be good to have some randomized clinical trials.”

For Dr. Levin, the bottom line is that all three treatments are associated with recovery for a majority of children. “This is good news for clinicians who have been guessing which treatment to use,” he said. “Both studies are attempts to provide doctors with some evidence on which to base treatment decisions and are not the final answer. Our study is ongoing, and with larger numbers of patients it may give clearer answers.”

The Overcoming COVID-19 study was funded by the U.S. Centers for Disease Control and Prevention. Several coauthors have reported support from industry outside of the submitted work. BATS was funded by the European Union’s Horizons 2020 Program. The study authors have disclosed no relevant financial relationships. One coauthor’s spouse is employed by GlaxoSmithKline. Dr. DeBiasi and Dr. Sexson Tejtel have disclosed no relevant financial relationships.

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

U.S. children and adolescents may be at higher risk for vaccine-preventable diseases this fall as vaccination levels have not caught up with prepandemic coverage, according to a study published in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

“Pediatric outbreaks of vaccine-preventable diseases have the potential to derail efforts to reopen schools for the 2021-22 academic year and further delay nationwide efforts to return students to the classroom,” wrote Bhavini Patel Murthy, MD, with the immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.

The number of children getting routine vaccinations plummeted between March and May 2020, compared with the same months in 2019. Although vaccination rates increased again from June 2020 to September 2020, the rebound was not enough to reach prepandemic levels, according to the study.

At the beginning of the June–September 2020 period, the news was good, the authors wrote. After most stay-at-home orders were lifted, the number of weekly routine pediatric vaccinations started to approach, and even surpass, baseline prepandemic levels in most of the 10 jurisdictions studied.

“However,” the authors wrote, “across all age groups and across all vaccine types, none of the jurisdictions demonstrated a sustained or prolonged increase in the number of weekly doses administered above prepandemic administration levels, which would have been necessary to catch up children and adolescents who missed routine vaccinations.”

To overcome the gap, the authors said that clinicians should take the initiative. “Health care providers should assess the vaccination status of all pediatric patients, including adolescents, and contact those who are behind schedule to ensure that all children are fully vaccinated.”

As COVID-19 vaccinations become more readily available to children, the CDC recommends that providers consider giving COVID-19 shots along with other routinely recommended vaccines.

Martha Perry, MD, associate professor and medical director at the University of North Carolina Children’s Primary Care Clinic, Chapel Hill, said in an interview that getting the message out about the need to get children and adolescents caught up may require a national messaging campaign similar to that for COVID-19 vaccinations, as well as opening mass vaccination sites rather than families seeking vaccinations from individual providers.

She noted that, although schools may offer a checks and balances system for required vaccinations, children who are not yet school age depend on families getting individual appointments.
 

Size of the gaps

The MMWR article shows that the shortfall in vaccinations in June–September 2020, compared with those months the year before are striking.

For children younger than 2 years old and aged 2-6 years, diphtheria, tetanus, and acellular pertussis (DtaP) vaccinations declined an average of 9.1% and 6.7%, respectively.

Among children aged 12-23 months and 2-8 years, MMR vaccinations decreased 8.8% and 11.3%, respectively.

Among children aged 9-12 years and adolescents 13-17 years, human papillomavirus vaccinations decreased an average 12.2% and 28.1%, respectively. Among the same age groups, Tdap vaccinations dropped 21.3% and 30.0%, respectively.

Dr. Perry said that, although all the shortfalls are important, lags in vaccinations for measles and pertussis are particularly alarming in light of outbreaks in recent years.

Additionally, she said, as COVID-19 restrictions are lifting, some of the mitigation strategies, such as mask wearing, that kept other diseases at bay will not be in place, heightening the risk for infection.

The authors chose to measure weekly doses in March–May 2020, and June–September 2020 because many jurisdictions imposed and then lifted stay-at-home orders during these times. They analyzed data from 10 jurisdictions with high-performing information systems (Idaho, Iowa, Louisiana, Michigan, Minnesota, New York City, North Dakota, Oregon, Washington, and Wisconsin).
 

Adults missing vaccinations as well

Another analysis, commissioned by GlaxoSmithKline and conducted by Avalere Health, calculated 8.8 million missed adolescent vaccine doses and 17.2 million missed adult vaccine doses as a result of the pandemic and ongoing government restrictions and public health measures.

That study examined claims for CDC-recommended vaccines across commercial, managed Medicaid, Medicare Advantage, and Medicare fee-for-service Part B for January–November 2020, compared with the same period in 2019. 

It also found that vaccine claims remain well below 2019 levels. Total noninfluenza vaccine claims submissions were down by between 13% and 35% among adolescents and 17% and 40% among adults, compared with the same period in 2019.

Dr. Perry said it will be critical for schools across the nation to enforce their policies on requiring up-to-date vaccinations even if online attendance is offered.

The workforce needed for this will be challenging, she noted.

“We’ve lost a lot of workforce in the health care field in the pandemic for a variety of reasons and it may be challenging to fill those positions,” she said.

She also said the study underlines the importance of each state having a vaccine registry so each provider can determine what vaccinations a child needs.

The study authors and Dr. Perry reported no relevant financial relationships.

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

U.S. children and adolescents may be at higher risk for vaccine-preventable diseases this fall as vaccination levels have not caught up with prepandemic coverage, according to a study published in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

“Pediatric outbreaks of vaccine-preventable diseases have the potential to derail efforts to reopen schools for the 2021-22 academic year and further delay nationwide efforts to return students to the classroom,” wrote Bhavini Patel Murthy, MD, with the immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.

The number of children getting routine vaccinations plummeted between March and May 2020, compared with the same months in 2019. Although vaccination rates increased again from June 2020 to September 2020, the rebound was not enough to reach prepandemic levels, according to the study.

At the beginning of the June–September 2020 period, the news was good, the authors wrote. After most stay-at-home orders were lifted, the number of weekly routine pediatric vaccinations started to approach, and even surpass, baseline prepandemic levels in most of the 10 jurisdictions studied.

“However,” the authors wrote, “across all age groups and across all vaccine types, none of the jurisdictions demonstrated a sustained or prolonged increase in the number of weekly doses administered above prepandemic administration levels, which would have been necessary to catch up children and adolescents who missed routine vaccinations.”

To overcome the gap, the authors said that clinicians should take the initiative. “Health care providers should assess the vaccination status of all pediatric patients, including adolescents, and contact those who are behind schedule to ensure that all children are fully vaccinated.”

As COVID-19 vaccinations become more readily available to children, the CDC recommends that providers consider giving COVID-19 shots along with other routinely recommended vaccines.

Martha Perry, MD, associate professor and medical director at the University of North Carolina Children’s Primary Care Clinic, Chapel Hill, said in an interview that getting the message out about the need to get children and adolescents caught up may require a national messaging campaign similar to that for COVID-19 vaccinations, as well as opening mass vaccination sites rather than families seeking vaccinations from individual providers.

She noted that, although schools may offer a checks and balances system for required vaccinations, children who are not yet school age depend on families getting individual appointments.
 

Size of the gaps

The MMWR article shows that the shortfall in vaccinations in June–September 2020, compared with those months the year before are striking.

For children younger than 2 years old and aged 2-6 years, diphtheria, tetanus, and acellular pertussis (DtaP) vaccinations declined an average of 9.1% and 6.7%, respectively.

Among children aged 12-23 months and 2-8 years, MMR vaccinations decreased 8.8% and 11.3%, respectively.

Among children aged 9-12 years and adolescents 13-17 years, human papillomavirus vaccinations decreased an average 12.2% and 28.1%, respectively. Among the same age groups, Tdap vaccinations dropped 21.3% and 30.0%, respectively.

Dr. Perry said that, although all the shortfalls are important, lags in vaccinations for measles and pertussis are particularly alarming in light of outbreaks in recent years.

Additionally, she said, as COVID-19 restrictions are lifting, some of the mitigation strategies, such as mask wearing, that kept other diseases at bay will not be in place, heightening the risk for infection.

The authors chose to measure weekly doses in March–May 2020, and June–September 2020 because many jurisdictions imposed and then lifted stay-at-home orders during these times. They analyzed data from 10 jurisdictions with high-performing information systems (Idaho, Iowa, Louisiana, Michigan, Minnesota, New York City, North Dakota, Oregon, Washington, and Wisconsin).
 

Adults missing vaccinations as well

Another analysis, commissioned by GlaxoSmithKline and conducted by Avalere Health, calculated 8.8 million missed adolescent vaccine doses and 17.2 million missed adult vaccine doses as a result of the pandemic and ongoing government restrictions and public health measures.

That study examined claims for CDC-recommended vaccines across commercial, managed Medicaid, Medicare Advantage, and Medicare fee-for-service Part B for January–November 2020, compared with the same period in 2019. 

It also found that vaccine claims remain well below 2019 levels. Total noninfluenza vaccine claims submissions were down by between 13% and 35% among adolescents and 17% and 40% among adults, compared with the same period in 2019.

Dr. Perry said it will be critical for schools across the nation to enforce their policies on requiring up-to-date vaccinations even if online attendance is offered.

The workforce needed for this will be challenging, she noted.

“We’ve lost a lot of workforce in the health care field in the pandemic for a variety of reasons and it may be challenging to fill those positions,” she said.

She also said the study underlines the importance of each state having a vaccine registry so each provider can determine what vaccinations a child needs.

The study authors and Dr. Perry reported no relevant financial relationships.

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

U.S. children and adolescents may be at higher risk for vaccine-preventable diseases this fall as vaccination levels have not caught up with prepandemic coverage, according to a study published in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.

“Pediatric outbreaks of vaccine-preventable diseases have the potential to derail efforts to reopen schools for the 2021-22 academic year and further delay nationwide efforts to return students to the classroom,” wrote Bhavini Patel Murthy, MD, with the immunization services division, National Center for Immunization and Respiratory Diseases, and colleagues.

The number of children getting routine vaccinations plummeted between March and May 2020, compared with the same months in 2019. Although vaccination rates increased again from June 2020 to September 2020, the rebound was not enough to reach prepandemic levels, according to the study.

At the beginning of the June–September 2020 period, the news was good, the authors wrote. After most stay-at-home orders were lifted, the number of weekly routine pediatric vaccinations started to approach, and even surpass, baseline prepandemic levels in most of the 10 jurisdictions studied.

“However,” the authors wrote, “across all age groups and across all vaccine types, none of the jurisdictions demonstrated a sustained or prolonged increase in the number of weekly doses administered above prepandemic administration levels, which would have been necessary to catch up children and adolescents who missed routine vaccinations.”

To overcome the gap, the authors said that clinicians should take the initiative. “Health care providers should assess the vaccination status of all pediatric patients, including adolescents, and contact those who are behind schedule to ensure that all children are fully vaccinated.”

As COVID-19 vaccinations become more readily available to children, the CDC recommends that providers consider giving COVID-19 shots along with other routinely recommended vaccines.

Martha Perry, MD, associate professor and medical director at the University of North Carolina Children’s Primary Care Clinic, Chapel Hill, said in an interview that getting the message out about the need to get children and adolescents caught up may require a national messaging campaign similar to that for COVID-19 vaccinations, as well as opening mass vaccination sites rather than families seeking vaccinations from individual providers.

She noted that, although schools may offer a checks and balances system for required vaccinations, children who are not yet school age depend on families getting individual appointments.
 

Size of the gaps

The MMWR article shows that the shortfall in vaccinations in June–September 2020, compared with those months the year before are striking.

For children younger than 2 years old and aged 2-6 years, diphtheria, tetanus, and acellular pertussis (DtaP) vaccinations declined an average of 9.1% and 6.7%, respectively.

Among children aged 12-23 months and 2-8 years, MMR vaccinations decreased 8.8% and 11.3%, respectively.

Among children aged 9-12 years and adolescents 13-17 years, human papillomavirus vaccinations decreased an average 12.2% and 28.1%, respectively. Among the same age groups, Tdap vaccinations dropped 21.3% and 30.0%, respectively.

Dr. Perry said that, although all the shortfalls are important, lags in vaccinations for measles and pertussis are particularly alarming in light of outbreaks in recent years.

Additionally, she said, as COVID-19 restrictions are lifting, some of the mitigation strategies, such as mask wearing, that kept other diseases at bay will not be in place, heightening the risk for infection.

The authors chose to measure weekly doses in March–May 2020, and June–September 2020 because many jurisdictions imposed and then lifted stay-at-home orders during these times. They analyzed data from 10 jurisdictions with high-performing information systems (Idaho, Iowa, Louisiana, Michigan, Minnesota, New York City, North Dakota, Oregon, Washington, and Wisconsin).
 

Adults missing vaccinations as well

Another analysis, commissioned by GlaxoSmithKline and conducted by Avalere Health, calculated 8.8 million missed adolescent vaccine doses and 17.2 million missed adult vaccine doses as a result of the pandemic and ongoing government restrictions and public health measures.

That study examined claims for CDC-recommended vaccines across commercial, managed Medicaid, Medicare Advantage, and Medicare fee-for-service Part B for January–November 2020, compared with the same period in 2019. 

It also found that vaccine claims remain well below 2019 levels. Total noninfluenza vaccine claims submissions were down by between 13% and 35% among adolescents and 17% and 40% among adults, compared with the same period in 2019.

Dr. Perry said it will be critical for schools across the nation to enforce their policies on requiring up-to-date vaccinations even if online attendance is offered.

The workforce needed for this will be challenging, she noted.

“We’ve lost a lot of workforce in the health care field in the pandemic for a variety of reasons and it may be challenging to fill those positions,” she said.

She also said the study underlines the importance of each state having a vaccine registry so each provider can determine what vaccinations a child needs.

The study authors and Dr. Perry reported no relevant financial relationships.

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

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

Swelling of the heart appears to be a very rare side effect that primarily strikes young people after vaccination for COVID-19, a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.

The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.

Telltale symptoms include chest pain, shortness of breath, and fever.

William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.

“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.

The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children. 

Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization.  Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.

“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.

Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
 

Adverse events reports

The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials. 

But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.

But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get. 

Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.

The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.

Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.

The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
 

More study needed

Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.

“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee. 

“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.

Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.

“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.

The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.

In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.

The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.

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

Swelling of the heart appears to be a very rare side effect that primarily strikes young people after vaccination for COVID-19, a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.

The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.

Telltale symptoms include chest pain, shortness of breath, and fever.

William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.

“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.

The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children. 

Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization.  Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.

“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.

Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
 

Adverse events reports

The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials. 

But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.

But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get. 

Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.

The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.

Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.

The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
 

More study needed

Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.

“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee. 

“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.

Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.

“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.

The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.

In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.

The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.

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

Swelling of the heart appears to be a very rare side effect that primarily strikes young people after vaccination for COVID-19, a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.

The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.

Telltale symptoms include chest pain, shortness of breath, and fever.

William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.

“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.

The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children. 

Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization.  Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.

“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.

Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
 

Adverse events reports

The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials. 

But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.

But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get. 

Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.

The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.

Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.

The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
 

More study needed

Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.

“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee. 

“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.

Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.

“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.

The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.

In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.

The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.

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

Children with food allergies often require diligent monitoring and a restricted diet to reduce allergic attacks, but there is little evidence available to support so-called “food bans” at schools and childcare centers.

Instead, a new practice guideline published earlier this month in the Journal of Allergy and Clinical Immunology calls for better allergy management training for staff, as well as increased epinephrine availability in educational environments. The guidelines were developed by an international panel of clinicians, school personnel, and parents.
 

The guidance at a glance

Rather than creating site-wide food prohibitions on nuts, dairy, and other allergenic foods, the practice guidance recommends centers and schools use “common-sense approaches” to reduce allergic reaction risk among school-aged children. According to the guideline authors, these strategies could include promoting handwashing, providing adult supervision during snacks and meals, and cleaning surfaces where food is either eaten or prepared.

Additionally, the new evidence-based guidance calls for schools and childcare centers to teach school personnel to recognize, prevent, and respond appropriately to food-related allergic reactions when they do occur.

The guidance also recommends that educational institutions require an up-to-date allergy ‘action plan’ from parents, designed for their children with allergies. These action plans can be integrated into the training of teachers and nurses to help manage potential allergic reactions.

Moreover, the guidance suggests schools should keep unassigned epinephrine autoinjectors in stock, both on site and even when traveling, where laws permit, rather than requiring students with allergies to bring in their own autoinjectors. Ultimately, this represents a more proactive approach to treating anaphylaxis, particularly in settings where treatment is urgently needed, such as when students are away from campus and participating in a school-designated trip or event.
 

Expert perspectives

Jennifer A. Dantzer, MD, MHS, allergist-immunologist and assistant professor of pediatrics at Johns Hopkins University, Baltimore, told this news organization via email that the practice guidelines offer an important starting point for ensuring quality of life of students, parents, and other school personnel.

While the Centers for Disease Control and Prevention published voluntary guidance for managing food allergies in schools back in 2013, there has since “been a lack of universal policies and procedures to manage the risk of allergic reactions in schools,” explained Dr. Dantzer. “The new guidelines are a good first step of using available evidence and all the key stakeholders, clinicians, school personnel, and families to figure out the best way to keep children with food allergies safe at school.”

Dr. Dantzer wasn’t involved in the creation of the new practice guidelines, but she shared how her clinical experience reinforces the need for the evidence-based recommendations. “Every single week we talk with families, both in clinic and in our research studies, about living with food allergies, and we recognize that every child is different,” she said. “We constantly work to advocate for each individual child with food allergies.”

Pediatric allergist Malika Gupta, MBBS, MD, said in an interview via email that the guidelines could assist in the creation of new nationwide policies for food allergy management at schools. “Also, the guidelines are labeled ‘conditional,’ which gives policymakers the ability to adapt to their specific circumstances and individuals, as well as make modifications according to regional trends,” she added.

Dr. Gupta, a clinical assistant professor in the Division of Allergy and Clinical Immunology at the University of Michigan, Ann Arbor, echoed the guideline panel’s sentiments regarding food bans, explaining that prohibiting certain foods could lend a “false sense of security” and could also “promote bullying and a sense of isolation for the food-allergic child.” In spite of the lack of evidence supporting food bans, Dr. Gupta noted that these bans can give families a sense of control and security. Ideally, more research should be performed to determine whether food bans actually work, she added.

In addition to promoting the new guidelines, allergists and pediatricians can also implement proactive allergy reaction mitigation strategies that work with school systems, according to Dr. Gupta. “In-clinic, we ensure all families have food allergy action plans for school and current epinephrine auto-injectors,” she said. “We also often have our food allergy nurses educate schools when food allergy awareness is a concern.”

Many of the 25 authors of the food allergy guidelines disclosed relevant financial relationships. The full list is with the original article. According to a footnote within the guidelines, “Panel members who were deemed to have a real, perceived, or potential conflict of interest were asked to abstain from voting on recommendations related to that interest.”  

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

Children with food allergies often require diligent monitoring and a restricted diet to reduce allergic attacks, but there is little evidence available to support so-called “food bans” at schools and childcare centers.

Instead, a new practice guideline published earlier this month in the Journal of Allergy and Clinical Immunology calls for better allergy management training for staff, as well as increased epinephrine availability in educational environments. The guidelines were developed by an international panel of clinicians, school personnel, and parents.
 

The guidance at a glance

Rather than creating site-wide food prohibitions on nuts, dairy, and other allergenic foods, the practice guidance recommends centers and schools use “common-sense approaches” to reduce allergic reaction risk among school-aged children. According to the guideline authors, these strategies could include promoting handwashing, providing adult supervision during snacks and meals, and cleaning surfaces where food is either eaten or prepared.

Additionally, the new evidence-based guidance calls for schools and childcare centers to teach school personnel to recognize, prevent, and respond appropriately to food-related allergic reactions when they do occur.

The guidance also recommends that educational institutions require an up-to-date allergy ‘action plan’ from parents, designed for their children with allergies. These action plans can be integrated into the training of teachers and nurses to help manage potential allergic reactions.

Moreover, the guidance suggests schools should keep unassigned epinephrine autoinjectors in stock, both on site and even when traveling, where laws permit, rather than requiring students with allergies to bring in their own autoinjectors. Ultimately, this represents a more proactive approach to treating anaphylaxis, particularly in settings where treatment is urgently needed, such as when students are away from campus and participating in a school-designated trip or event.
 

Expert perspectives

Jennifer A. Dantzer, MD, MHS, allergist-immunologist and assistant professor of pediatrics at Johns Hopkins University, Baltimore, told this news organization via email that the practice guidelines offer an important starting point for ensuring quality of life of students, parents, and other school personnel.

While the Centers for Disease Control and Prevention published voluntary guidance for managing food allergies in schools back in 2013, there has since “been a lack of universal policies and procedures to manage the risk of allergic reactions in schools,” explained Dr. Dantzer. “The new guidelines are a good first step of using available evidence and all the key stakeholders, clinicians, school personnel, and families to figure out the best way to keep children with food allergies safe at school.”

Dr. Dantzer wasn’t involved in the creation of the new practice guidelines, but she shared how her clinical experience reinforces the need for the evidence-based recommendations. “Every single week we talk with families, both in clinic and in our research studies, about living with food allergies, and we recognize that every child is different,” she said. “We constantly work to advocate for each individual child with food allergies.”

Pediatric allergist Malika Gupta, MBBS, MD, said in an interview via email that the guidelines could assist in the creation of new nationwide policies for food allergy management at schools. “Also, the guidelines are labeled ‘conditional,’ which gives policymakers the ability to adapt to their specific circumstances and individuals, as well as make modifications according to regional trends,” she added.

Dr. Gupta, a clinical assistant professor in the Division of Allergy and Clinical Immunology at the University of Michigan, Ann Arbor, echoed the guideline panel’s sentiments regarding food bans, explaining that prohibiting certain foods could lend a “false sense of security” and could also “promote bullying and a sense of isolation for the food-allergic child.” In spite of the lack of evidence supporting food bans, Dr. Gupta noted that these bans can give families a sense of control and security. Ideally, more research should be performed to determine whether food bans actually work, she added.

In addition to promoting the new guidelines, allergists and pediatricians can also implement proactive allergy reaction mitigation strategies that work with school systems, according to Dr. Gupta. “In-clinic, we ensure all families have food allergy action plans for school and current epinephrine auto-injectors,” she said. “We also often have our food allergy nurses educate schools when food allergy awareness is a concern.”

Many of the 25 authors of the food allergy guidelines disclosed relevant financial relationships. The full list is with the original article. According to a footnote within the guidelines, “Panel members who were deemed to have a real, perceived, or potential conflict of interest were asked to abstain from voting on recommendations related to that interest.”  

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

Children with food allergies often require diligent monitoring and a restricted diet to reduce allergic attacks, but there is little evidence available to support so-called “food bans” at schools and childcare centers.

Instead, a new practice guideline published earlier this month in the Journal of Allergy and Clinical Immunology calls for better allergy management training for staff, as well as increased epinephrine availability in educational environments. The guidelines were developed by an international panel of clinicians, school personnel, and parents.
 

The guidance at a glance

Rather than creating site-wide food prohibitions on nuts, dairy, and other allergenic foods, the practice guidance recommends centers and schools use “common-sense approaches” to reduce allergic reaction risk among school-aged children. According to the guideline authors, these strategies could include promoting handwashing, providing adult supervision during snacks and meals, and cleaning surfaces where food is either eaten or prepared.

Additionally, the new evidence-based guidance calls for schools and childcare centers to teach school personnel to recognize, prevent, and respond appropriately to food-related allergic reactions when they do occur.

The guidance also recommends that educational institutions require an up-to-date allergy ‘action plan’ from parents, designed for their children with allergies. These action plans can be integrated into the training of teachers and nurses to help manage potential allergic reactions.

Moreover, the guidance suggests schools should keep unassigned epinephrine autoinjectors in stock, both on site and even when traveling, where laws permit, rather than requiring students with allergies to bring in their own autoinjectors. Ultimately, this represents a more proactive approach to treating anaphylaxis, particularly in settings where treatment is urgently needed, such as when students are away from campus and participating in a school-designated trip or event.
 

Expert perspectives

Jennifer A. Dantzer, MD, MHS, allergist-immunologist and assistant professor of pediatrics at Johns Hopkins University, Baltimore, told this news organization via email that the practice guidelines offer an important starting point for ensuring quality of life of students, parents, and other school personnel.

While the Centers for Disease Control and Prevention published voluntary guidance for managing food allergies in schools back in 2013, there has since “been a lack of universal policies and procedures to manage the risk of allergic reactions in schools,” explained Dr. Dantzer. “The new guidelines are a good first step of using available evidence and all the key stakeholders, clinicians, school personnel, and families to figure out the best way to keep children with food allergies safe at school.”

Dr. Dantzer wasn’t involved in the creation of the new practice guidelines, but she shared how her clinical experience reinforces the need for the evidence-based recommendations. “Every single week we talk with families, both in clinic and in our research studies, about living with food allergies, and we recognize that every child is different,” she said. “We constantly work to advocate for each individual child with food allergies.”

Pediatric allergist Malika Gupta, MBBS, MD, said in an interview via email that the guidelines could assist in the creation of new nationwide policies for food allergy management at schools. “Also, the guidelines are labeled ‘conditional,’ which gives policymakers the ability to adapt to their specific circumstances and individuals, as well as make modifications according to regional trends,” she added.

Dr. Gupta, a clinical assistant professor in the Division of Allergy and Clinical Immunology at the University of Michigan, Ann Arbor, echoed the guideline panel’s sentiments regarding food bans, explaining that prohibiting certain foods could lend a “false sense of security” and could also “promote bullying and a sense of isolation for the food-allergic child.” In spite of the lack of evidence supporting food bans, Dr. Gupta noted that these bans can give families a sense of control and security. Ideally, more research should be performed to determine whether food bans actually work, she added.

In addition to promoting the new guidelines, allergists and pediatricians can also implement proactive allergy reaction mitigation strategies that work with school systems, according to Dr. Gupta. “In-clinic, we ensure all families have food allergy action plans for school and current epinephrine auto-injectors,” she said. “We also often have our food allergy nurses educate schools when food allergy awareness is a concern.”

Many of the 25 authors of the food allergy guidelines disclosed relevant financial relationships. The full list is with the original article. According to a footnote within the guidelines, “Panel members who were deemed to have a real, perceived, or potential conflict of interest were asked to abstain from voting on recommendations related to that interest.”  

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