Therapy helps peanut-allergic kids tolerate tablespoons of peanut butter
NIH trial informs potential treatment strategy for kids who already tolerate half a peanut or more
image:
Container of peanut butter with a spoon.
view moreCredit: NIAID
Eating gradually increasing doses of store-bought, home-measured peanut butter for about 18 months enabled 100% of children with peanut allergy who initially could tolerate the equivalent of at least half a peanut to consume three tablespoons of peanut butter without an allergic reaction, researchers report. This easy-to-implement treatment strategy could potentially fulfill an unmet need for about half of children with peanut allergy, who already can tolerate the equivalent of at least half a peanut, considered a high threshold. The findings come from a trial sponsored and funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and published today in the journal NEJM Evidence.
“Children with high-threshold peanut allergy couldn’t participate in previous food allergy treatment trials, leaving them without opportunities to explore treatment options,” said NIAID Director Jeanne Marrazzo, M.D., M.P.H. “Today’s report focuses on this population and shows that a very safe and accessible form of therapy could be liberating for many of these children and their families.”
The food allergy treatments currently approved by the Food and Drug Administration were tested in children with low-threshold peanut allergy, who cannot tolerate the equivalent of even half a peanut. These treatments are designed to decrease the likelihood of a reaction to a small amount of peanut despite efforts to avoid it, as might occur with accidental exposure. This approach is not relevant to the estimated 800,000 U.S. children who may have high-threshold peanut allergy, leaving them with only one management strategy prior to the new report: peanut avoidance.
To address this need, researchers tested whether a low-cost, convenient treatment strategy could help children with high-threshold peanut allergy tolerate a much greater amount of peanut protein than they already did. The mid-stage trial involved 73 children ages 4 to 14 years. Based on parent or guardian report, nearly 60% of the children were white, 19% were Asian, 1.4% were Black, and 22% were more than one race. The study team assigned the children at random to either test the new treatment strategy or continue avoiding peanut.
Those in the peanut-ingestion group began with a minimum daily dose of 1/8 teaspoon of peanut butter. They gradually increased their dose every eight weeks up to 1 tablespoon of peanut butter or an equivalent amount of a different peanut product, such as peanut flour or candies. Dose increases took place under medical supervision at the study site. None of the children in the peanut-ingestion group needed epinephrine to treat severe allergic reactions during home dosing, and only one child needed epinephrine during a supervised dosing visit at the study site.
After undergoing the treatment regimen, the peanut-consuming children participated in an oral food challenge carefully supervised by the study team to see how much peanut butter they could eat without an allergic reaction. All 32 children who participated in the challenge could tolerate the maximum amount of 9 grams of peanut protein, the equivalent of 3 tablespoons of peanut butter. By contrast, only three of the 30 children in the avoidance group who underwent the oral food challenge after a similar amount of time in the trial could tolerate 9 grams of peanut protein. Three additional children in the avoidance group tolerated a challenge dose at least two doses greater than the amount they could tolerate at the start of the study.
The trial took place during the COVID-19 pandemic, and some families preferred to avoid indoor close contact with others at that time, so some children did not return to the study site for the oral food challenge. Using a common statistical technique to account for those missing challenge results, 100% of the ingestion group and 21% of the avoidance group tolerated at least two doses greater than they could at the outset.
Children in the peanut-ingestion group who could tolerate 9 grams of peanut protein during the oral food challenge consumed at least 2 tablespoons of peanut butter weekly for 16 weeks, then avoided peanut entirely for eight weeks. At that point, they were asked to return to the study site for a final oral food challenge.
Twenty-six of the 30 treated children (86.7%) who participated in the final challenge continued to tolerate 9 grams of peanut protein, indicating they had achieved sustained unresponsiveness to peanut. The three children in the avoidance group who could eat 9 grams of peanut protein without a reaction at the earlier challenge were considered to have developed natural tolerance to peanut. Analyzing these outcomes and including all 73 children who began the trial, regardless of whether they participated in the final challenge, investigators found that 68.4% of the peanut-ingestion group achieved sustained unresponsiveness, while only 8.6% of the avoidance group developed natural tolerance.
Based on these encouraging results, the investigators want to learn if the same treatment strategy would work for food allergens other than peanuts. Future follow-up is needed to determine the therapy’s effectiveness at inducing long-lasting tolerance of peanut.
Scott H. Sicherer, M.D., and Julie Wang, M.D., led the trial, which took place at the Elliot and Roslyn Jaffe Food Allergy Institute in Mount Sinai Kravis Children’s Hospital, New York. Dr. Sicherer is director of the Institute and the Elliot and Roslyn Jaffe Professor of Pediatric Allergy and Immunology. He is also chief of the Division of Allergy and Immunology in the Department of Pediatrics and medical director of the Clinical Research Unit in the ConduITS Institute for Translational Sciences at Icahn School of Medicine at Mount Sinai. Dr. Wang is a professor of pediatric allergy and immunology in the Elliot and Roslyn Jaffe Food Allergy Institute.
More information about the clinical trial, called the CAFETERIA study, is available at ClinicalTrials.gov under study identifier NCT03907397.
Reference: SH Sicherer et al. Randomized trial of high dose, home measured peanut oral immunotherapy in children with high threshold peanut allergy. NEJM Evidence DOI: 10.1056/EVIDoa2400306 (2025).
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov/.
NIH...Turning Discovery Into Health®
Journal
NEJM Evidence
DOI
Eating gradually increasing doses of store-bought peanut butter enables children with high-threshold allergy to safely consume peanuts
The Mount Sinai Hospital / Mount Sinai School of Medicine
image:
peanut butter
view moreCredit: rusvaplauke on flickr (https://www.flickr.com/photos/7440954@N05/488467362)
Children with high-threshold peanut allergy who ate gradually larger doses of store-bought peanut butter achieved significantly higher and long-lasting rates of desensitization compared to those who avoided peanuts, according to a new study led by researchers at the Icahn School of Medicine at Mount Sinai.
Results of the trial, sponsored and funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, appear in the Monday, February 10 issue of NEJM Evidence [https://doi.org/10.1056/EVIDoa2400306].
“Our study results suggest a safe, inexpensive and effective pathway for allergists to treat children with peanut allergy who can already tolerate the equivalent of at least half a peanut, considered a high-threshold peanut allergy,” said Scott Sicherer, MD, Director of the Elliot and Roslyn Jaffe Food Allergy Institute at Mount Sinai Kravis Children’s Hospital, Chief of the Division of Allergy and Immunology in Mount Sinai’s Department of Pediatrics, and lead author of the paper. “Our findings open the gateway to personalized threshold-based treatments of food allergy and will encourage additional studies that delve deeper into peanut and other foods for this approach that might be a game-changer for the majority of people with food allergies.”
The most common approach to a food allergy is to avoid the food, but in recent years peanut oral immunotherapy—medically supervised, very gradual daily feeding of increasing amounts of pharmaceutical-grade peanut protein—has become an option for individuals with peanut allergies.. However, studies that led to Food and Drug Administration approval of an injected biologic and oral peanut immunotherapy have specifically focused on people who react to very small amounts of food allergens, such as half a peanut or less (considered a low-thershold peanut allergy). There are an estimated 800,000 children in the United States with high threshold peanut allergy who might benefit from the treatment strategy examined in this study.
“Years ago, when people with milk and egg allergies were advised to undertake strict avoidance, our team initiated studies that found most people with milk and egg allergies could tolerate these foods in baked goods, which changed the global approach to these allergies,” said Julie Wang, MD, Professor of Pediatrics at the Icahn School of Medicine, clinical researcher at the Jaffe Food Allergy Institute, and co-senior author of the paper. “The research team recognized that more than half of people with peanut allergy can tolerate half a peanut or more, and thought that this group of people might be treatable if we took a different approach to peanut oral immunotherapy. We were thrilled to find that this treatment strategy was even more successful than we had anticipated.”
To test this hypothesis, the study team recruited 73 children ages 4 to 14 years old. Study participants were assigned, at random, to either test the new treatment strategy or continue avoiding peanuts. The children in the peanut-ingestion group began with a minimum daily dose of 1/8 teaspoon of peanut butter and gradually increased their dose every eight weeks over the course of 18 months, ending at one tablespoon of peanut butter or an equivalent amount of a different peanut product. All dose increases took place under medical supervision. None of the study participants in the peanut-ingestion group had severe reactions or needed epinephrine during home dosing and only one received epinephrine during a supervised dosing visit.
Following the treatment regimen, children from the peanut-consuming cohort participated in a feeding test, carefully supervised by the study team, to evaluate how much peanut they could eat without an allergic reaction. All 32 children from the peanut-consuming group who participated in the feeding test could tolerate the maximum amount of nine grams of peanut protein, or three tablespoons of peanut butter. By contrast, only three of the 30 children from the avoidance group who underwent the feeding test after avoiding peanuts for the duration of the study could tolerate this amount.
Because the trial took place during the COVID-19 pandemic and some families preferred avoiding close encounters indoors, some did not return to the study site for the feeding test. Using a common statistical technique to account for the children who missed the feeding test, the team reported that 100 percent of the ingestion group and 21 percent of the avoidance group tolerated an oral food challenge that was at least two doses more than they could tolerate at the beginning of the study.
To test if the response to treatment was durable, children in the peanut-ingestion group who could tolerate nine grams of protein during the feeding test went on to consume at least two tablespoons of peanut butter weekly for 16 weeks and then avoided peanuts entirely for eight weeks. Twenty-six of the 30 treated children who participated in a final feeding test after the eight-week abstinence period continued to tolerate nine grams of peanut protein, indicating that they had achieved sustained unresponsiveness to peanuts. The three participants from the avoidance group who could eat nine grams of peanut protein without reaction at the earlier food test were considered to have developed natural tolerance to peanuts. A comprehensive analysis of data collected from all 73 study participants revealed that 68.4 percent of the peanut-ingestion group achieved sustained unresponsiveness, while only 8.6 percent of the avoidance group developed a natural tolerance.
“These study results are very exciting and a huge step forward in personalizing food allergy treatment,” concluded Dr. Sicherer, the Elliot and Roslyn Jaffe Professor in Pediatric Allergy and Immunology at Mount Sinai. “My hope is that this study will eventually change practice to help these children and encourage additional research that includes this approach for more foods.”
In addition to expanding the work to more foods and validation studies of their approach, the Mount Sinai study team aims to determine a better way of identifying individuals with higher thresholds, because the best way to do so currently requires a feeding test that is bound to cause an allergic reaction.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.
###
Journal
NEJM Evidence
Method of Research
Experimental study
Subject of Research
People
Article Title
Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy
Article Publication Date
10-Feb-2025
