Immunology

LOS ANGELES – A sublingual immunotherapy tablet for house dust mite–induced allergic rhinitis achieved clinically meaningful improvement in symptoms along with less use of rescue medications and a favorable safety profile in a pivotal phase III trial, Dr. Hendrik Nolte reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The double-blind, 52-week randomized trial included 1,482 North American adults and adolescents.

“This was the largest clinical trial ever conducted with sublingual therapy in North America, and the first successful North American trial of a house dust mite sublingual immunotherapy tablet. It confirms results from previous large European trials,” noted Dr. Nolte of Merck, which is collaborating with the Danish company ALK in developing this therapy.

The sublingual immunotherapy (SLIT) tablet, known for now as the 12 SQ HDM SLIT-tablet, has been approved by European regulatory authorities for treatment of adults with house dust mite (HDM) allergic rhinitis or HDM allergic asthma. Based upon the positive findings in the phase III U.S. trial, Merck applied in February 2016 to the U.S. Food and Drug Administration for approval of the tablet as a biologic agent in patients aged 12 years or older.

HDM is the most common indoor allergen in the world. Unlike pollen and ragweed allergies, it’s not a seasonal problem. Moreover, HDM-induced allergic rhinitis is associated with increased risk of asthma. Although HDM allergic rhinitis can be treated symptomatically with oral antihistamines and nasal steroids, allergy immunotherapy has the appeal of addressing the underlying disease mechanism and potentially altering the long-term course. SLIT using a highly standardized HDM allergen extract offers a major advantage over traditional allergy immunotherapy via a lengthy program of subcutaneous injections – namely, the convenience of home self-administration.

The primary endpoint in the U.S. pivotal trial was the total combined rhinitis score (TCRS), which is the sum of the daily rhinitis symptom score and the daily rescue medication usage score averaged over the last 8 weeks of the year-long study. The FDA has set the bar for establishing clinically meaningful improvement: it requires demonstration of a reduction in the TCRS of at least 15%, compared with placebo. The 12 SQ HDM SLIT-tablet trial exceeded this standard, achieving a 17% reduction. The study also met its key prespecified secondary endpoints, including a 16% reduction in the daily rhinosinusitis symptom score and an 18% decrease in the daily medication score, compared with placebo.

©Eraxion/Thinkstock

Participants in the trial had a mean 18-year history of allergic rhinitis with or without conjunctivitis. Seventy-five percent of them were sensitized to other common allergens in addition to HDM, and 31% of subjects had comorbid asthma. The HDM SLIT therapy was equally effective in asthmatics and nonasthmatics, in patients allergic only to HDM and those who were polysensitized, and in subjects with and without conjunctivitis, according to Dr. Nolte.

There were no serious adverse events related to the 12 SQ HDM SLIT-tablet. A total of 9.8% of patients discontinued SLIT because of treatment-emergent adverse events, chiefly mild-to-moderate throat irritation, mouth swelling, or itchiness of the mouth or ears.

“Importantly, these events were very transient. They occurred typically within the first 8 days and lasted 14-67 hours, with a median 1-day duration of rescue medication,” he said.

Symptomatic improvement was typically seen beginning at 8-12 weeks. Adults were free to take the once-daily tablet anytime during the day. The pediatric patients were advised not to do so in the morning because they wouldn’t be under observation while on a school bus.

The tablet is based upon a formulation of allergen extracts from the two major species of HDM: Dermatophagoides pterornyssinus and D. farinae. More than 90% of HDM-sensitized patients are sensitized to both. A highly standardized manufacturing process ensures that the tablet contains 50 mcg of the four major HDM allergens in equal ratio – Der f1, Der p2, Der p1, and Der f 2 – plus other components.

In response to audience questions, Dr. Nolte said the company had tried incorporating an antihistamine into the tablet to block adverse reactions but it didn’t work. Adverse events typically occur within a couple of minutes after taking the tablet, and antihistamines are far too slow-acting to help.

“You can premedicate with antihistamines. We know European investigators and clinicians who are doing it. But I would not recommend it personally, because these tablets are taken at home after the first administration in the office, and I think it’s important that the patient has a good feel for what happens over the following days. There is a potential risk of masking side effects with premedication, which could be a concern,” Dr. Nolte said.

Merck already has two FDA-approved SLIT tablets developed with ALK on the U.S. market: Grastek, for treatment of grass pollen–induced allergic rhinitis in children and adults, and Ragwitek, for ragweed-induced allergic disease in adults.

The trial was sponsored by Merck and presented by a full-time company employee.

LOS ANGELES – A sublingual immunotherapy tablet for house dust mite–induced allergic rhinitis achieved clinically meaningful improvement in symptoms along with less use of rescue medications and a favorable safety profile in a pivotal phase III trial, Dr. Hendrik Nolte reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The double-blind, 52-week randomized trial included 1,482 North American adults and adolescents.

“This was the largest clinical trial ever conducted with sublingual therapy in North America, and the first successful North American trial of a house dust mite sublingual immunotherapy tablet. It confirms results from previous large European trials,” noted Dr. Nolte of Merck, which is collaborating with the Danish company ALK in developing this therapy.

The sublingual immunotherapy (SLIT) tablet, known for now as the 12 SQ HDM SLIT-tablet, has been approved by European regulatory authorities for treatment of adults with house dust mite (HDM) allergic rhinitis or HDM allergic asthma. Based upon the positive findings in the phase III U.S. trial, Merck applied in February 2016 to the U.S. Food and Drug Administration for approval of the tablet as a biologic agent in patients aged 12 years or older.

HDM is the most common indoor allergen in the world. Unlike pollen and ragweed allergies, it’s not a seasonal problem. Moreover, HDM-induced allergic rhinitis is associated with increased risk of asthma. Although HDM allergic rhinitis can be treated symptomatically with oral antihistamines and nasal steroids, allergy immunotherapy has the appeal of addressing the underlying disease mechanism and potentially altering the long-term course. SLIT using a highly standardized HDM allergen extract offers a major advantage over traditional allergy immunotherapy via a lengthy program of subcutaneous injections – namely, the convenience of home self-administration.

The primary endpoint in the U.S. pivotal trial was the total combined rhinitis score (TCRS), which is the sum of the daily rhinitis symptom score and the daily rescue medication usage score averaged over the last 8 weeks of the year-long study. The FDA has set the bar for establishing clinically meaningful improvement: it requires demonstration of a reduction in the TCRS of at least 15%, compared with placebo. The 12 SQ HDM SLIT-tablet trial exceeded this standard, achieving a 17% reduction. The study also met its key prespecified secondary endpoints, including a 16% reduction in the daily rhinosinusitis symptom score and an 18% decrease in the daily medication score, compared with placebo.

©Eraxion/Thinkstock

Participants in the trial had a mean 18-year history of allergic rhinitis with or without conjunctivitis. Seventy-five percent of them were sensitized to other common allergens in addition to HDM, and 31% of subjects had comorbid asthma. The HDM SLIT therapy was equally effective in asthmatics and nonasthmatics, in patients allergic only to HDM and those who were polysensitized, and in subjects with and without conjunctivitis, according to Dr. Nolte.

There were no serious adverse events related to the 12 SQ HDM SLIT-tablet. A total of 9.8% of patients discontinued SLIT because of treatment-emergent adverse events, chiefly mild-to-moderate throat irritation, mouth swelling, or itchiness of the mouth or ears.

“Importantly, these events were very transient. They occurred typically within the first 8 days and lasted 14-67 hours, with a median 1-day duration of rescue medication,” he said.

Symptomatic improvement was typically seen beginning at 8-12 weeks. Adults were free to take the once-daily tablet anytime during the day. The pediatric patients were advised not to do so in the morning because they wouldn’t be under observation while on a school bus.

The tablet is based upon a formulation of allergen extracts from the two major species of HDM: Dermatophagoides pterornyssinus and D. farinae. More than 90% of HDM-sensitized patients are sensitized to both. A highly standardized manufacturing process ensures that the tablet contains 50 mcg of the four major HDM allergens in equal ratio – Der f1, Der p2, Der p1, and Der f 2 – plus other components.

In response to audience questions, Dr. Nolte said the company had tried incorporating an antihistamine into the tablet to block adverse reactions but it didn’t work. Adverse events typically occur within a couple of minutes after taking the tablet, and antihistamines are far too slow-acting to help.

“You can premedicate with antihistamines. We know European investigators and clinicians who are doing it. But I would not recommend it personally, because these tablets are taken at home after the first administration in the office, and I think it’s important that the patient has a good feel for what happens over the following days. There is a potential risk of masking side effects with premedication, which could be a concern,” Dr. Nolte said.

Merck already has two FDA-approved SLIT tablets developed with ALK on the U.S. market: Grastek, for treatment of grass pollen–induced allergic rhinitis in children and adults, and Ragwitek, for ragweed-induced allergic disease in adults.

The trial was sponsored by Merck and presented by a full-time company employee.

LOS ANGELES – A sublingual immunotherapy tablet for house dust mite–induced allergic rhinitis achieved clinically meaningful improvement in symptoms along with less use of rescue medications and a favorable safety profile in a pivotal phase III trial, Dr. Hendrik Nolte reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The double-blind, 52-week randomized trial included 1,482 North American adults and adolescents.

“This was the largest clinical trial ever conducted with sublingual therapy in North America, and the first successful North American trial of a house dust mite sublingual immunotherapy tablet. It confirms results from previous large European trials,” noted Dr. Nolte of Merck, which is collaborating with the Danish company ALK in developing this therapy.

The sublingual immunotherapy (SLIT) tablet, known for now as the 12 SQ HDM SLIT-tablet, has been approved by European regulatory authorities for treatment of adults with house dust mite (HDM) allergic rhinitis or HDM allergic asthma. Based upon the positive findings in the phase III U.S. trial, Merck applied in February 2016 to the U.S. Food and Drug Administration for approval of the tablet as a biologic agent in patients aged 12 years or older.

HDM is the most common indoor allergen in the world. Unlike pollen and ragweed allergies, it’s not a seasonal problem. Moreover, HDM-induced allergic rhinitis is associated with increased risk of asthma. Although HDM allergic rhinitis can be treated symptomatically with oral antihistamines and nasal steroids, allergy immunotherapy has the appeal of addressing the underlying disease mechanism and potentially altering the long-term course. SLIT using a highly standardized HDM allergen extract offers a major advantage over traditional allergy immunotherapy via a lengthy program of subcutaneous injections – namely, the convenience of home self-administration.

The primary endpoint in the U.S. pivotal trial was the total combined rhinitis score (TCRS), which is the sum of the daily rhinitis symptom score and the daily rescue medication usage score averaged over the last 8 weeks of the year-long study. The FDA has set the bar for establishing clinically meaningful improvement: it requires demonstration of a reduction in the TCRS of at least 15%, compared with placebo. The 12 SQ HDM SLIT-tablet trial exceeded this standard, achieving a 17% reduction. The study also met its key prespecified secondary endpoints, including a 16% reduction in the daily rhinosinusitis symptom score and an 18% decrease in the daily medication score, compared with placebo.

©Eraxion/Thinkstock

Participants in the trial had a mean 18-year history of allergic rhinitis with or without conjunctivitis. Seventy-five percent of them were sensitized to other common allergens in addition to HDM, and 31% of subjects had comorbid asthma. The HDM SLIT therapy was equally effective in asthmatics and nonasthmatics, in patients allergic only to HDM and those who were polysensitized, and in subjects with and without conjunctivitis, according to Dr. Nolte.

There were no serious adverse events related to the 12 SQ HDM SLIT-tablet. A total of 9.8% of patients discontinued SLIT because of treatment-emergent adverse events, chiefly mild-to-moderate throat irritation, mouth swelling, or itchiness of the mouth or ears.

“Importantly, these events were very transient. They occurred typically within the first 8 days and lasted 14-67 hours, with a median 1-day duration of rescue medication,” he said.

Symptomatic improvement was typically seen beginning at 8-12 weeks. Adults were free to take the once-daily tablet anytime during the day. The pediatric patients were advised not to do so in the morning because they wouldn’t be under observation while on a school bus.

The tablet is based upon a formulation of allergen extracts from the two major species of HDM: Dermatophagoides pterornyssinus and D. farinae. More than 90% of HDM-sensitized patients are sensitized to both. A highly standardized manufacturing process ensures that the tablet contains 50 mcg of the four major HDM allergens in equal ratio – Der f1, Der p2, Der p1, and Der f 2 – plus other components.

In response to audience questions, Dr. Nolte said the company had tried incorporating an antihistamine into the tablet to block adverse reactions but it didn’t work. Adverse events typically occur within a couple of minutes after taking the tablet, and antihistamines are far too slow-acting to help.

“You can premedicate with antihistamines. We know European investigators and clinicians who are doing it. But I would not recommend it personally, because these tablets are taken at home after the first administration in the office, and I think it’s important that the patient has a good feel for what happens over the following days. There is a potential risk of masking side effects with premedication, which could be a concern,” Dr. Nolte said.

Merck already has two FDA-approved SLIT tablets developed with ALK on the U.S. market: Grastek, for treatment of grass pollen–induced allergic rhinitis in children and adults, and Ragwitek, for ragweed-induced allergic disease in adults.

The trial was sponsored by Merck and presented by a full-time company employee.

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

[email protected]

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

[email protected]

LOS ANGELES – Food doses as low as 300 mg every other day are enough to retain tolerance in the maintenance phase of pediatric oral immunotherapy for food allergies, according to an investigation involving 62 children over 4 years of age.

The flexibility “to take smaller doses and still maintain desensitization” is why “a lot of our patients continued to do regular dosing of their oral immunotherapy” for up to 6 years, said Dr. Sharon Chinthrajah, a pediatric allergist and immunologist at Stanford (Calif.) University.

The children were originally involved in phase I testing of desensitization for multiple food allergies with omalizumab (Xolair). By reducing the risk of anaphylaxis, the biologic facilitated rapid escalation: 30 children on omalizumab tolerated 2-g food challenges by 9 months. It took about 2 years for 43 children to reach that level without omalizumab.

Subjects had up to five allergies from a list of 15, including egg, milk, and peanut. When tolerance was achieved, they stayed on daily 2-g dosing of each of their food allergens for 4-6 months. They and their parents were then given the option of 2-g daily maintenance dosing or dropping down to as low as 300 mg – about the equivalent of one tree nut – every other day.

The investigators reported follow-up data for 62 subjects at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. Nine children on omalizumab and 22 who did not get omalizumab stuck with 2 g–daily dosing, while 18 omalizumab and 13 no-omalizumab children opted for lower maintenance dosing.

They all remained largely tolerant to 2-g challenges every 6 months for up to 46 months in the omalizumab group and 73 months in the no-omalizumab group, the end of follow-up in each group. There were no differences in immunologic parameters and no differences in tolerance testing between the two groups, and tolerance was maintained regardless of the food allergen. Only about 0.5% of reactions in either group were severe.

“We were excited to find that going down to 300 mg was just as protective” and that long-term maintenance dosing is safe, said Dr. Kari Nadeau, professor of pediatric immunology and allergy at the university. “These are important messages. There’s not a lot of follow-up data on food [oral immunotherapy]. Patient flexibility is key to long-term outcomes,” she added.

“I think people who had milk, egg, and wheat allergies probably didn’t reduce their intake during maintenance, since these are the ones they tend to enjoy,” Dr. Chinthrajah said, but the risk of severe reactions remains, “so we still require patients to carry reaction medication, and review autoinjector use when they come back to our center for testing and food challenges.”

There was no industry funding for the work, and the investigators said they have no relevant disclosures.

[email protected]

Findings on the use of hydrolyzed formula in place of standard cows’ milk formula to prevent allergy in high-risk infants do not support current guidelines, according to Dr. Robert J Boyle of Imperial College London and his associates.

A review and meta-analysis were performed on 28 randomized control trials, 6 quasirandomized trials, and 3 controlled clinical trials describing allergic or autoimmune outcomes, with more than 19,000 participants. Among 13 studies reporting on the risk of food allergy, no significant difference was found in the risk of any food allergy with partially hydrolyzed formula (risk ratio, 1.73; 95% confidence interval, 0.79-3.80) and extensively hydrolyzed formula (RR, 0.86; CI, 0.26-2.82), compared with standard formula at age 0-4 years, and for extensively hydrolyzed formula at age 5-14 years.

©patrisyu/Thinkstock

The review also examined and found no significant evidence favoring the use of hydrolyzed formula in place of standard cows’ milk formula to avert the risk of eczema, wheeze, allergic rhinitis, or type 1 diabetes mellitus.

The researchers suggest that guidelines be updated and revised to reflect these new findings.

“We found no consistent evidence to support the current recommendations and found evidence of publication bias, methodological biases, and conflict of interest in those studies reporting allergic outcomes,” Dr. Boyle and his associates concluded. “We suggest that any future trials on hydrolyzed formula should be prospectively registered, independently funded, and include adequate oversight to ensure that they do not negatively impact on breastfeeding in study participants”.

Read the full study at the British Medical Journal (doi: 10.1136/bmj.i974)

Findings on the use of hydrolyzed formula in place of standard cows’ milk formula to prevent allergy in high-risk infants do not support current guidelines, according to Dr. Robert J Boyle of Imperial College London and his associates.

A review and meta-analysis were performed on 28 randomized control trials, 6 quasirandomized trials, and 3 controlled clinical trials describing allergic or autoimmune outcomes, with more than 19,000 participants. Among 13 studies reporting on the risk of food allergy, no significant difference was found in the risk of any food allergy with partially hydrolyzed formula (risk ratio, 1.73; 95% confidence interval, 0.79-3.80) and extensively hydrolyzed formula (RR, 0.86; CI, 0.26-2.82), compared with standard formula at age 0-4 years, and for extensively hydrolyzed formula at age 5-14 years.

©patrisyu/Thinkstock

The review also examined and found no significant evidence favoring the use of hydrolyzed formula in place of standard cows’ milk formula to avert the risk of eczema, wheeze, allergic rhinitis, or type 1 diabetes mellitus.

The researchers suggest that guidelines be updated and revised to reflect these new findings.

“We found no consistent evidence to support the current recommendations and found evidence of publication bias, methodological biases, and conflict of interest in those studies reporting allergic outcomes,” Dr. Boyle and his associates concluded. “We suggest that any future trials on hydrolyzed formula should be prospectively registered, independently funded, and include adequate oversight to ensure that they do not negatively impact on breastfeeding in study participants”.

Read the full study at the British Medical Journal (doi: 10.1136/bmj.i974)

Findings on the use of hydrolyzed formula in place of standard cows’ milk formula to prevent allergy in high-risk infants do not support current guidelines, according to Dr. Robert J Boyle of Imperial College London and his associates.

A review and meta-analysis were performed on 28 randomized control trials, 6 quasirandomized trials, and 3 controlled clinical trials describing allergic or autoimmune outcomes, with more than 19,000 participants. Among 13 studies reporting on the risk of food allergy, no significant difference was found in the risk of any food allergy with partially hydrolyzed formula (risk ratio, 1.73; 95% confidence interval, 0.79-3.80) and extensively hydrolyzed formula (RR, 0.86; CI, 0.26-2.82), compared with standard formula at age 0-4 years, and for extensively hydrolyzed formula at age 5-14 years.

©patrisyu/Thinkstock

The review also examined and found no significant evidence favoring the use of hydrolyzed formula in place of standard cows’ milk formula to avert the risk of eczema, wheeze, allergic rhinitis, or type 1 diabetes mellitus.

The researchers suggest that guidelines be updated and revised to reflect these new findings.

“We found no consistent evidence to support the current recommendations and found evidence of publication bias, methodological biases, and conflict of interest in those studies reporting allergic outcomes,” Dr. Boyle and his associates concluded. “We suggest that any future trials on hydrolyzed formula should be prospectively registered, independently funded, and include adequate oversight to ensure that they do not negatively impact on breastfeeding in study participants”.

Read the full study at the British Medical Journal (doi: 10.1136/bmj.i974)

LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.

“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.

Bruce Jancin/Frontline Medical News

A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.

The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.

In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).

Bruce Jancin/Frontline Medical News

The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.

Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.

These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.

“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.

The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.

Bruce Jancin/Frontline Medical News

“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.

“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”

Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.

The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.

Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).

LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.

LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.

“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.

Bruce Jancin/Frontline Medical News

A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.

The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.

In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).

Bruce Jancin/Frontline Medical News

The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.

Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.

These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.

“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.

The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.

Bruce Jancin/Frontline Medical News

“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.

“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”

Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.

The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.

Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).

LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.

LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.

“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.

Bruce Jancin/Frontline Medical News

A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.

The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.

In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).

Bruce Jancin/Frontline Medical News

The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.

Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.

These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.

“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.

The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.

Bruce Jancin/Frontline Medical News

“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.

“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”

Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.

The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.

Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).

LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.