Small Doses Of Peanut Protein Turns Allergies Around – Clinical Trial

by NCN Health And Science Team Posted on November 19th, 2018

Houston, Texas, USA : Carefully calibrated doses of peanut protein can turn extreme allergies around. At the end of a year of slowly increasing exposure, most children who started off severely allergic could eat the equivalent of two peanuts.

That reversal, reported November 18 in the New England Journal of Medicine, “will be considered life-transforming for many families with a peanut allergy,” says pediatric allergist Michael Perkin of St. George’s, University of London, who wrote an accompanying editorial in the same issue of NEJM. The findings were also presented on the same day at the annual meeting of the American College of Allergy, Asthma and Immunology in Seattle.

Peanut exposure came in the form of a drug called AR101, described in the study as a “peanut-derived investigational biologic oral immunotherapy drug,” or, as Perkin puts it, “peanut flour in a capsule.” Unlike a sack of peanut flour, AR101 is carefully meted out, such that the smallest doses used in the study contained precisely 0.5 milligrams of peanut protein — the equivalent of about one six-hundredth of a large peanut.

In the clinical trial, 372 children ages 4 to 17 years began taking the lowest dose of AR101. The doses increased in peanut protein every two weeks until the kids topped out at 300 milligrams, which is about that of a single peanut.

For the next 24 weeks, participants, located in the United States, Canada and Europe, took that dose daily. When the trial ended, all of the participants were challenged with increasing doses of peanut protein under close supervision. Two-thirds of the 372 children who received the peanut protein regimen, or 250 participants, could tolerate a peanut protein dose of at least 600 milligrams, comparable to about two peanuts. In contrast, only five of the 124 children who received placebos, or 4 percent, could tolerate the same dose. (A smaller number of adults ages 18 to 55 were enrolled in the study, but didn’t show big improvements.)

That improved tolerance “can really change the lives of patients who are peanut allergic,” says study coauthor Daniel Adelman, an allergist and immunologist at Aimmune Therapeutics, a company based in Brisbane, Calif., that makes AR101 and sponsored the trial.

The goal of the therapy is to guard against the potentially dangerous effects of accidental peanut exposures, such as a child mistakenly taking a bite of a friend’s PB&J. “What we’re trying to do is free people up from the fear and anxiety associated with the potential bad things that can happen with minute quantities of peanut exposure,” Adelman says.

During the study, nearly all of the participants who received the drug had allergic reactions to it — reactions that were expected, since “you’re giving people the thing they’re allergic to,” Adelman says. Most of those reactions weren’t severe, such as a rash or slight abdominal pain.

Although the drug is made of peanut protein, parents, or even doctors, shouldn’t attempt a similar treatment by measuring peanut protein themselves, experts say. Without exact measurements, peanut exposure could be dangerous. “This is treating peanut like a medicine, not a food,” says pediatric allergist Scott Sicherer of the Icahn School of Medicine at Mount Sinai in New York City. “Don’t try this at home.”

Schicher also cautions that, while the regimen is promising, it is not a cure. It’s not yet clear how long people would need consistent peanut protein exposure to maintain their tolerance, but regular use is probably needed. “It has to be a routine,” he says.

Citation : The Palisade Group of Clinical Investigators. AR101 oral immunotherapy for peanut allergy. New England Journal of Medicine. doi: 10.1056/NEJMe1813314.

Peanut Allergy: Early Exposure Is Key to Prevention

With peanut allergy on the rise in the United States, you’ve probably heard parents strategizing about ways to keep their kids from developing this potentially dangerous condition. But is it actually possible to prevent peanut allergy, and, if so, how do you go about doing it?

There’s an entirely new strategy emerging now! A group representing 26 professional organizations, advocacy groups, and federal agencies, including the National Institutes of Health (NIH), has just issued new clinical guidelines aimed at preventing peanut allergy [1]. The guidelines suggest that parents should introduce most babies to peanut-containing foods around the time they begin eating other solid foods, typically 4 to 6 months of age. While early introduction is especially important for kids at particular risk for developing allergies, it is also recommended that high-risk infants—those with a history of severe eczema and/or egg allergy—undergo a blood or skin-prick test before being given foods containing peanuts. The test results can help to determine how, or even if, peanuts should be introduced in the youngsters’ diets.

This recommendation is turning older guidelines on their head. In the past, pediatricians often advised parents to delay introducing peanuts and other common causes of food allergies into their kids’ diets. But in 2010, the thinking began shifting when a panel of food allergy experts concluded insufficient evidence existed to show that delaying the introduction of potentially problematic foods actually protected kids [2]. Still, there wasn’t a strategy waiting to help prevent peanut or other food allergies.

As highlighted in a previous blog entry, the breakthrough came in 2015 with evidence from the NIH-funded Learning Early about Peanut Allergy (LEAP) trial [3]. That trial, involving hundreds of babies under a year old at high risk for developing peanut allergy, established that kids could be protected by regularly eating a popular peanut butter-flavored Israeli snack called Bamba. A follow-up study later showed those kids remained allergy-free even after avoiding peanuts for a year [4].

Under the new recommendations, published simultaneously in six journals including the Journal of Allergy and Clinical Immunology, all infants who don’t already test positive for a peanut allergy are encouraged to eat peanut-enriched foods soon after they’ve tried a few other solid foods. The guidelines are the first to offer specific recommendations for allergy prevention based on a child’s risk for peanut allergy:

  • Infants at high risk for peanut allergy—based on severe eczema and/or egg allergy—are suggested to begin consuming peanut-enriched foods between 4 to 6 months of age, but only after parents check with their health care providers. Infants already showing signs of peanut sensitivity in blood and/or skin-prick tests should try peanuts for the first time under the supervision of their doctor or allergist. In some cases, test results indicating a strong reaction to peanut protein might lead a specialist to recommend that a particular child avoid peanuts.
  • Infants with mild to moderate eczema should incorporate peanut-containing foods into their diets by about 6 months of age. It’s generally OK for them to have those first bites of peanut at home and without prior testing.
  • Infants without eczema or any other food allergy aren’t likely to develop an allergy to peanuts. To be on the safe side, it’s still a good idea for them to start eating peanuts from an early age.

Once peanut-containing foods have been consumed safely, regular exposure is key to allergy prevention. The guidelines recommend that infants—and particularly those at the greatest risk of allergies—eat about 2 grams of peanut protein (the amount in 2 teaspoons of peanut butter) 3 times a week.

Of course, it’s never a good idea to give infants whole peanuts, which are a choking hazard. Infants should instead get their peanuts in prepared peanut-containing foods or by stirring peanut powder into other familiar foods. They might also try peanut butter spread on bread or crackers.

In recent years, peanut allergy in the U.S. has nearly quadrupled, making it the leading cause of death due to severe, food-related allergic reactions. The hope is that, with widespread implementation of these new guidelines, many new cases of peanut allergy can now be prevented.

LEAP Study

Given its severe nature and the absence of a cure, prevention remains our best hope to reduce peanut allergy in children. But how exactly can peanut allergy be prevented? Does eating peanuts during infancy make the immune system tolerant or sensitive to peanuts consumed later on? Does one approach work better than the other in preventing peanut allergy in children? These are the important questions the LEAP Study seeks to answer.

LEAP (Learning Early About Peanut allergy) is a randomized controlled clinical trial designed and conducted by the Immune Tolerant Network (ITN) to determine the best strategy to prevent peanut allergy in young children. 640 children between 4 and 11 months of age who were identified as high risk for peanut allergy, based on an existing egg allergy and/or severe eczema, were enrolled in the study.

The children were randomly assigned to two groups – avoidance or consumption:

Study Group Instructions until the age of 5
Consumption Consume a peanut containing snack with three or more meals (equivalent to 6 grams of peanut protein each week)
Avoidance Do not ingest peanut-containing foods

The proportion of each group that develops peanut allergy by 5 years of age will be used to determine which approach – avoidance or consumption – works best for preventing peanut allergy.

All participants received allergy testing, dietary counselling, physical examinations and were asked to provide occasional blood samples for use in examining differences in immune system development in each of the study groups.

LEAP Study Results

In 2008, NIAID established a coordinating committee composed of professional organizations, federal agencies, and patient advocacy groups to oversee development of concise clinical guidelines on the diagnosis and management of food allergy and the treatment of acute food allergy reactions. Developed over two years, the 2010 Guidelines for the Diagnosis and Management of Food Allergy in the United States offer evidence-based recommendations for health care professionals.

In 2015, findings from a landmark NIAID-funded clinical trial called the Learning Early About Peanut (LEAP) study showed that introducing peanut-containing foods to infants at high risk for developing peanut allergy was safe and led to an 81 percent relative reduction in the subsequent development of peanut allergy. Based on the strength of these results, NIAID established another coordinating committee, which convened an expert panel to update the 2010 Guidelines to specifically address the prevention of peanut allergy. The Addendum Guidelines for the Prevention of Peanut Allergy in the United States were published in January 2017.

The results of the Immune Tolerance Network’s (ITN) “Learning Early About Peanut” (LEAP), discussed on February 23, 2015 at the American Academy of Allergy, Asthma & Immunology Annual Meeting and published in the New England Journal of Medicine, demonstrate that consumption of a peanut-containing snack by infants who are at high-risk for developing peanut allergy prevents the subsequent development of allergy. The LEAP study, designed and conducted by the ITN with additional support from FARE and led by Professor Gideon Lack at Kings College London, is the first randomized trial to prevent food allergy in a large cohort of high-risk infants.

Peanut allergy is an aberrant response by the body’s immune system to harmless peanut proteins in the diet. The prevalence of peanut allergy has doubled over the past 10 years in the US and other countries that advocate avoidance of peanuts during pregnancy, lactation, and infancy. The LEAP study was based on a hypothesis that regular eating of peanut-containing products, when started during infancy, will elicit a protective immune response instead of an allergic immune reaction.

Over 600 children between 4 and 11 months of age at high risk for peanut allergy were randomized to either consume or avoid peanut until age 5 in order to compare the incidence of peanut allergy between the two groups. Children in the peanut consumption arm of the trial ate a peanut-containing snack-food at least three times each week, while children in the peanut avoidance arm did not ingest peanut-containing foods.

Of the children who avoided peanut, 17% developed peanut allergy by the age of 5 years. Remarkably, only 3% of the children who were randomized to eating the peanut snack developed allergy by age 5. Therefore, in high-risk infants, sustained consumption of peanut beginning in the first 11 months of life was highly effective in preventing the development of peanut allergy.

“For decades allergists have been recommending that young infants avoid consuming allergenic foods such as peanut to prevent food allergies,” notes Professor Lack, the lead investigator for the LEAP study. “Our findings suggest that this advice was incorrect and may have contributed to the rise in the peanut and other food allergies.”

LEAP-ON Study Results

The results of the Immune Tolerance Network’s (ITN) “Persistence of Oral Tolerance to Peanut” (LEAP-ON), discussed on March 4, 2016 at the American Academy of Allergy, Asthma & Immunology Annual Meeting and published in the New England Journal of Medicine, demonstrate that peanut allergy prevention achieved from early peanut consumption in at-risk infants persists after a one-year period of avoiding peanut.

The LEAP-ON Study, designed and conducted by the ITN and led by Professor Gideon Lack at Kings College London was an extension of the ITN’s landmark LEAP Study (Learning Early About Peanut Allergy), which demonstrated that regular peanut consumption begun in early infancy and continued until age 5 reduced the rate of peanut allergy in at-risk infants by 80% compared to non-peanut-consumers.

LEAP-ON examined the question of whether participants who had consumed peanut for more than four years were protected long-term against peanut allergy when they stopped eating peanut. The study followed 556 of the original 640 children in LEAP (both consumers and avoiders) for a one-year period of peanut avoidance. This cohort included 274 previous peanut consumers and 282 previous peanut avoiders.

After 12 months of peanut avoidance, only 4.8% of the original peanut consumers were found to be allergic, compared to 18.6% of the original peanut avoiders, a highly significant difference.

“This study offers reassurance that eating peanut-containing foods as part of a normal diet—with occasional periods of time without peanut—will be a safe practice for most children following successful tolerance therapy,” said Dr. Gerald Nepom, Director of the Immune Tolerance Network. “The immune system appears to remember and sustain its tolerant state, even without continuous regular exposure to peanuts.”

Peanut allergy

Peanut allergies are very similar to other allergies, which are abnormal responses by the body’s immune system to otherwise harmless substances. In a peanut allergic child, when the immune system detects peanut protein, antibodies are produced that trigger an inappropriate immune response.

Over the past several decades, faced with the growing problem of peanut allergy, health authorities in the UK, Canada, and US recommended that children at high risk for peanut allergy should not eat any peanut-containing foods under the age of three. More recently however, scientists have begun calling this strategy into question. Many scientists now believe that by repeatedly exposing the child’s immune system to peanut at an early age, their body learns to tolerate the peanut proteins. Evidence for this theory comes from several other countries whose children typically consume high levels of peanut protein from infancy onwards, yet fail to show the high rates of peanut allergy observed in Western countries where peanut is generally avoided in early life.

There is currently no cure for peanut allergy. Children who are allergic to peanuts must take great care to be vigilant in avoiding all traces of peanut from their diet. In addition, peanut allergic children often need to wear a Medic-Alert bracelet and, at all times, carry a pre-loaded adrenaline (epinephrine) injection kit with them for use in event of a severe reaction.

What happens during an allergic reaction to peanut?

The allergic reaction to peanut occurs soon after exposure (usually through ingestion). Typical immediate allergic reactions include the development of hives on the face or body; blotching around the mouth (which may spread to the rest of the body); immediate runny nose, sneezing and itchy-watery eyes; coughing; choking or gagging; wheezing and trouble breathing; and cramps, vomiting and diarrhea. Although allergic reactions are usually mild to moderate in severity and usually terminate spontaneously or after the administration of an antihistamine, severe reactions – known as anaphylaxis – can occur. Anaphylaxis is a severe allergic reaction which involves several parts of the body and can be fatal if not treated immediately.

Why is peanut allergy a problem?

The prevalence of peanut allergy has doubled over the past 10 years in countries that advocate avoidance of peanuts during pregnancy, lactation and infancy. Peanut allergy now affects approximately 1.5% of young children and is often diagnosed in children less than 2 years old.

While there are many types of food allergies, peanut allergies are particularly troublesome, for a number of reasons. Foremost is the fact that peanut allergy often results in more severe reactions than other food allergies, up to and including sudden death. In addition, other than the complete avoidance of peanut, there is currently no available therapy for the treatment of peanut allergy. Importantly, symptoms can occur following exposure to only very tiny (or ‘trace’) amounts of peanut protein. Because peanuts are used in a wide variety of food products, trace amounts of peanut protein can be found in many foods – from chocolate bars to fruit snacks, making avoidance difficult.

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