Consuming peanut products from infancy through age 5 years provided lasting tolerance into adolescence without the need to regularly upkeep consumption, according to a study published in NEJM Evidence.Findings come from the LEAP-Trio study, which builds on the results from the LEAP study and the following LEAP-On study, both of which were sponsored by the National Institute of Allergy and Infectious Diseases.
“The results from the original LEAP study, which was published almost 10 years ago now, showed that introducing peanut products to infants before the first year of life resulted in protection from peanut allergy developing later,” Patricia Fulkerson, MD, PhD, chief of NIAID’s Food Allergy, Atopic Dermatitis, and Allergic Mechanisms Section, told Healio. “The last time they checked on these kids, it was around 6 years of age and so, they wanted to see if it was durable. This protection was durable all the way into adolescence,” Fulkerson, who was not an author on the study, continued.
The trial examined the durability of peanut tolerance at 144 months (12 years) of age with at-will peanut consumption, eating or avoiding peanuts as desired. Enrollment took place from July 2018 to August 2022. In the original LEAP study, 640 infants aged 4 to 11 months with severe eczema, egg allergy or both were randomly assigned to consume or avoid peanuts until reaching age 60 months. In the current study, researchers evaluated 508 (79.4%; mean age, 13 years) of these children, including 253 from the original peanut avoidance group and 255 from the original peanut consumption group.
The primary outcome of the LEAP-Trio study was the number of participants with a peanut allergy at 144 months of age. This was determined by either an oral food challenge or self-reporting from participants who consumed at least 2 g of peanut protein during a single occasion without a reaction in the prior year. Allergy status for the remaining participants was determined by a prediction model using biomarker data. From the 508 participants, 497 had sufficient data to determine peanut allergy, 400 (80.5%) of which underwent an OFC to establish allergic status.
Within the intention-to-treat analysis, 15.4% of 246 children in the peanut avoidance group and 4.4% of 251 children in the peanut consumption group at 144 months had peanut allergy (P < 0.001), showing a 71% reduction in the prevalence of peanut allergy with consumption. Among early peanut consumption participants who originally had a negative skin prick test, 2.8% of 213 children manifested a peanut allergy in the consumption group at 144 months compared with 12.7% of 205 children in the avoidance group. Among participants who initially had a positive SPT, 29.3% of 41 children were allergic in the avoidance group compared with 13.2% of 38 children in the consumption group. Researchers show that overall, there was a 75% reduction in the prevalence of peanut allergy during the lifespan of the LEAP-Trio participants.
“The most important findings were that the kids are still well protected,” Fulkerson said. “When they were babies, they were at high risk for developing food allergies, and peanut allergy is not an allergy that’s often outgrown. It’s persistent to adulthood. And so, when we checked, when they were around 13 years of age, they were still well protected.” In the LEAP-Trio per-protocol analysis, which included 470 children, peanut allergy was present in 15.1% of 232 participants in the avoidance group and 0.8% of 238 participants in the consumption group, showing a 14.2 (95% CI, 9.5-19) percentage point difference between groups. The effect size was similar in SPT negative and positive groups with an 11.1% difference (95% CI, 6.3%-15.9%) and 29.3% difference (95% CI, 15.3%-43.2%) between the avoidance and consumption groups. Peanut consumption varied widely among both groups in the 4 weeks before the 144-month assessment. The consumption group participants ate a geometric mean of 2.9 ± 12 g, and the avoidance group participants ate 0.2 ± 20.6 g (ratio of geometric means, 12.2; 95% CI, 7.2-20.5).
Researchers also reported significant diversity in peanut consumption in both the avoidance and consumption groups in years following their last LEAP or LEAP-On visits. Among yearly intervals, 26.8% to 33.1% of the consumption group reported eating 50 g or less of peanuts per year, and 13.3% to 15.1% reported avoiding any consumption for more than 6 months at a time. “The most surprising finding was that it didn't really matter how much peanut they ate,” Fulkerson said. “So, they had to ingest peanut in order to avoid developing the peanut allergy. But once that protection was set in place, they didn't have to keep ingesting it. So many of these kids stopped eating peanut for months at a time and they were still well protected from developing food allergies.”
At 144 months, mean SPT wheals were 1.4 ± 2.6 mm in the consumption group and 2.8 ± 4.7 mm in the avoidance group, for a –1.4 mm mean difference (95% CI, –2.1 to –0.7 mm). The geometric mean levels of Ara h 2-specific IgE were 0.03 ± 3.42 µg/L in the consumption group and 0.06 ± 11.2 µg/L in the avoidance group (ratio of geometric means, 0.4; 95% CI, 0.3-0.7). Ara h 6-specific peanut IgE levels included 0.03 ± 3.04 µg/L in the consumption group and 0.06 ± 10.75 µg/L in the avoidance group, demonstrating a ratio of geometric means of 0.4 (95% CI, 0.3-0.6) For peanut-specific IgG4, geometric mean levels were 535.5 ± 5 µg/L in the consumption group and 209.3 ± 3.8 µg/L in the avoidance group (ratio of geometric means, 2.6; 95% CI, 1.9 to 3.4).
Fulkerson said that these findings can assuage parents and doctors about the feasibility of early introduction and its long-term effects. “This isn’t something that has to be done for their entire lifetime,” she said. “They can only do it for a short period of time in these early years and they’ll be protected for at least until the 13-year mark.” In the future, researchers hope to expand their study into other food groups. “The evidence is clear for peanuts,” Fulkerson said. “But, what about early introduction of other foods? We don’t really have good, strong data to support the introduction of these other allergens. But that’s something that we want to build on as well.”
Reference: Du Toit G, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1414850.
Dr. Sara Dever from Allergy & Asthma Care of Fairfield County, LLC comments: "We've known since the LEAP study that early introduction of peanut into the diet reduces the risk of peanut allergy. This study demonstrates that tolerance of peanut persists into teenage years and likely beyond, even if the child stops eating peanut regularly. The benefits of early introduction of other foods will likely be found to similar, but we await further data on other foods."
