麻豆传媒

Children originally part of a peanut consumption trial maintained long-lasting peanut tolerance by age 12, a follow-up of the LEAP trial found.

At 12 years of age, just 4.4% of high-risk kids given early introduction of peanut allergens from infancy to age 5 years reported a peanut allergy compared with 15.4% among peers in a peanut avoidance arm, representing a 71% reduction in allergy prevalence (P<0.001), reported Gideon Lack, MBBCh, of King's College London, and coauthors.

Importantly, peanut consumption patterns after age 5 were not associated with development of peanut allergy.

"Our trial provides clinical evidence that induction of tolerance by early introduction of peanut led to a sustained tolerance to oral intake of peanut," the group wrote in . "The duration of protection, which persisted in the vast majority of participants in the LEAP trial, from at least age 6 to age 13 years, is consistent with the notion that true tolerance was achieved through this intervention."

In a , National Institute of Allergy and Infectious Diseases (NIAID) Director Jeanne Marrazzo, MD, MPH, said the "findings should reinforce parents' and caregivers' confidence that feeding their young children peanut products beginning in infancy according to established guidelines can provide lasting protection from peanut allergy."

"If widely implemented, this safe, simple strategy could prevent tens of thousands of cases of peanut allergy among the 3.6 million children born in the United States each year," Marrazzo added.

The clinical trial originally included infants who were considered to be high-risk for peanut allergies -- having severe eczema, egg allergy, or both. These patients were then randomized to either avoid or consume peanut products until they reached 5 years of age. Early introduction was found to reduce the risk of developing a peanut allergy at 5 years by about 81%. Patients in both groups developed peanut-specific IgE antibodies.

Later, the continuation trial had pediatric participants avoid peanut products for an additional year, until they reached 6 years old. Many children who had previously consumed peanuts stayed protected from peanut allergy risk; nonallergic individuals were allowed to eat peanuts as they wished, while the allergic individuals at the end of LEAP-On were instructed to continue peanut avoidance.

In both peanut eating and abstinence groups, there was a wide range of average weekly peanut consumption since their last LEAP or LEAP-on visit and in the 4 weeks preceding the 12-year assessment. However, concentrations of peanut protein on an assay at the 12-year visit showed differences between groups -- 34.8 ug/g vs 10.6 ug/g in the peanut consumption and control groups, respectively.

Researchers noted that greater levels of ad libitum consumption among original peanut consumption patients in LEAP-Trio trial could have provided ongoing protection through what they describe as "ad hoc desensitization."

This, plus the risk of recall bias, may have potentially limited the findings of the study.

The current analysis provided long-term follow-up of 508 of the original 640 LEAP trial children. In addition, researchers assessed siblings and parents of LEAP participants for peanut allergies and parental characteristics that may predict food allergy development, respectively. Younger siblings of LEAP participants were shown to have levels of peanut allergen sensitization in a prior report.

In order to be eligible for the present follow-up, former LEAP participants needed to be ages 9.5 years or older.

Of the 470 children who participated in the LEAP-Trio trial per-protocol analysis, 15.1% of avoidance patients and 0.8% of consumption patients presented with an established peanut allergy.

The impacts of peanut consumption on the primary endpoint of peanut allergy rates among the population was also observed in patients who originally had a negative skin-prick test. Of those with negative skin-prick tests who avoided peanut consumption, 12.7% reported a manifestation of peanut allergies, compared to 2.8% of that same group who consumed peanuts.

Among participants with positive skin-prick test results, 29.3% of participants who avoided peanuts and 13.2% of participants who consumed peanuts reported manifestations of peanut allergies. Skin-prick findings were consistent when race and ethnic identity were included in analyses; consumption was associated with a 75% decrease in the lifetime peanut allergy prevalence.

After 12 years, the average wheal sizes in the peanut consumption group were 1.4 mm and 4.7 mm in the peanut avoidance group.

Lack and colleagues reported that at age 12, the peanut consumption patients had average Ara h2-specific IgE levels of 0.03 kU/L and levels of peanut-specific immunoglobulin (Ig) G4 of 535.5 μg/L, while avoidance patients had average Ara h2-specific IgE levels of 0.06 kU/L and levels of peanut-specific IgG4 of 209.3 μg/L.

"Clinically, LEAP-Trio demonstrates that early introduction of peanuts in high-risk children results in long-lived tolerance. That long-lasting tolerance to peanuts is induced by ingestion during an early developmental window suggests that gastrointestinal exposure is important, though the underlying immunological mechanisms of protection from allergy remain unclear," commented Michael Dougan, MD, PhD, of Massachusetts General Hospital in Boston, and coauthors, in an .

"The few children who did develop peanut allergy between LEAP and LEAP-Trio showed a decrease in peanut-specific IgG4 with an increase in IgE. Together, these data support an important role of peanut-specific IgG4 in tolerance established by early peanut consumption," they added.

The editorialists urged further research regarding the mechanisms of the tolerance observed in the LEAP-Trio study.

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