Effect of Avoidance on Peanut Allergy after Early Peanut Consumption

Abstract

Background: In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group).

Methods: At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age.

Results: We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio.

Conclusions: Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.).

Figure 1.. Primary Outcome.

The prevalence of peanut allergy at 72 months of age is shown among participants who had a negative result on the skin-prick test (SPT) at the baseline visit in the primary trial, among those who had a positive result at the baseline visit, and in both groups combined. In the primary trial, participants at high risk for allergy had been randomly assigned to consume peanuts beginning in the first 11 months of life (peanut-consumption group) or avoid peanuts (peanut-avoidance group). Panel A shows the prevalence of peanut allergy at 60 months of age among only the participants in the primary trial who enrolled in the follow-up study. Panel B shows the prevalence of peanut allergy at 72 months of age among participants in the follow-up study who were included in the intention-to-treat analysis (i.e., all enrolled participants in the follow-up study who had a peanut-allergy outcome that could be evaluated). Panel C shows the prevalence of peanut allergy at 72 months of age among participants who met the per-protocol criteria in both the primary trial and the follow-up study. The main per-protocol criterion in the primary trial was adequate adherence to the randomized assignment to consume or avoid peanuts; the main per-protocol criterion in the follow-up study was adequate adherence to avoidance of peanut protein over a period of 12 months.

Figure 2.. Immunologic Outcomes in the Peanut-Avoidance and Peanut-Consumption Groups, from Baseline to 72 Months of Age.

Data are shown for participants who met the per-protocol criteria for both the primary trial and the follow-up study. Panel A shows the Ara h2–specific and peanut-specific IgE titers and wheal sizes on skin-prick testing for peanut. (Ara h2 is a component of peanut protein.) The level of Ara h2–specific IgE was assessed in all available participants who had a peanut-specific IgE level that was greater than or equal to 0.1 kU per liter at any visit (approximately 60% of the participants). Panel B shows peanut-specific IgG4 levels and IgG4:IgE ratios. The solid black lines show the group mean over the course of the study period. The thin red lines represent the trajectory among participants who had a peanut allergy at 72 months of age. Dots represent individual participants (blue indicates that the participant did not have peanut allergy, and red indicates allergy at 72 months). The gray shading represents the density of the distribution of the dots for participants who met the per-protocol criteria for both the primary trial and the follow-up study. The density of the distribution facilitates visual comparisons over time and between groups, which is not easily achievable with display of the individual dots alone, owing to a large amount of over-plotting. The log₁₀ of the ratio of peanut-specific IgG4:IgE was calculated after peanut-specific IgE levels were converted from kilo unit per liter to nanograms per milliliter with the use of the formula (IgG4 ÷ [IgE × 2.4]).

Figure 3.. Immunologic Outcomes According to Differing or Stable Allergy Status between Months 60 and 72.

Participants were categorized as “stayed allergic,” “stayed tolerant,” “became allergic,” or “no longer allergic.” Shown are the Ara h2–specific IgE antibody levels, peanut-specific IgE level, wheal size on skin-prick testing for peanut, peanut-specific IgG4 level, and IgG4:IgE ratios at the five assessments during the primary trial and the follow-up study. Data are shown only for participants who met the per-protocol criteria in both the primary trial and the follow-up study. At month 72, a total of 46 participants in the peanut-avoidance group and 1 in the peanut-consumption group were determined by the investigators to be still allergic, 202 in the peanut-avoidance group and 186 in the peanut-consumption group were still not allergic, 3 in the peanut-avoidance group and 3 in the peanut-consumption group became allergic, and 4 in the peanut-avoidance group and 0 in the peanut-consumption group no longer had allergy. Lines represent population means. The log₁₀ of the ratio of peanut-specific IgG4:IgE was calculated after peanut-specific IgE levels were converted from kilo unit per liter to nanograms per milliliter with the use of the formula (IgG4 ÷ [IgE × 2.4]).