Randomized trial of peanut consumption in infants at risk for peanut allergy

Abstract

Background: The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy.

Methods: We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test--one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age.

Results: Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy.

Conclusions: The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.).

Figure 1. Enrollment and Randomization

Baseline visits occurred when participants were at least 4 months of age but younger than 11 months of age. Participants randomly assigned to peanut consumption who had a positive response to the oral food challenge administered at baseline were instructed not to eat peanuts but were included in the intentionto-treat analysis. Only participants who adequately adhered to treatment were included in the per-protocol analysis. Adequate adherence to treatment was defined in the peanut-avoidance group as consumption of less than 0.2 g of peanut protein (the equivalent of one peanut) on any occasion and less than 0.5 g over a single week in the first 2 years of life. In the peanut-consumption group, adequate adherence was defined as consumption of at least 2 g of peanut protein on at least one occasion in both the first and second years of life and of at least 3 g of peanut protein (25 g of Bamba [a snack food made from peanut butter and puffed maize] or 12 g of peanut butter) per week for at least 50% of the weeks during which data were recorded. SPT denotes skin-prick test.

Figure 2. Primary Outcome

The prevalence of peanut allergy at 60 months of age is shown among participants who had a negative result on the skin-prick test at baseline, among those who had a positive result at baseline, and in both groups combined, in the intention-to-treat analysis (Panel A) and the per-protocol analysis (Panel B). Among the 640 participants who underwent randomization, peanut-allergy status was determined by means of an oral food challenge in 617 (96.4%) and by means of a diagnostic algorithm in 11 (1.7%). Peanut allergy could not be evaluated with the use of the diagnostic algorithm in 2 participants (0.3%). A total of 10 participants (1.6%) voluntarily withdrew or were lost to follow-up. The worst-case imputation analysis (Panel C) assumes that participants with missing data in the peanut-consumption group would have been allergic to peanuts and that participants with missing data in the peanut-avoidance group would have been nonallergic. P values are based on chi-square analyses.

Figure 3. Immunologic Outcomes for the Peanut-Avoidance and Peanut-Consumption Groups at Baseline (4 to <11 Months of Age) and at 12, 30, and 60 Months of Age

Panel A shows wheal sizes after the peanut-specific skin-prick test and the levels of peanut-specific IgE in participants in the avoidance and consumption groups who met the per-protocol criteria. The solid black lines show the group mean over the course of the study period; the mean wheal size after the peanut-specific skinprick test differed significantly between the randomized groups at all time points after baseline (P = 0.002 at 12 months and P<0.001 at 30 months and 60 months). The thin red lines represent the trajectory of the development of allergic responses among participants who were allergic at 60 months of age. Panel B shows the levels of peanut-specific IgG and IgG4 and the peanutspecific IgG4:IgE ratio over the course of the study period. The means of each of these measures differed significantly between the two study groups at all postbaseline time points (P<0.001). The log₁₀ of the ratio of peanut-specific IgG4:IgE was calculated after peanut-specific IgG4 levels were converted from milligrams per liter to nanograms per milliliter and the peanut-specific IgE levels were converted from kilo unit per liter to nanograms per milliliter with the use of the formula (IgG4 × 1000) ÷ (IgE × 2.4).