Early Exposure of Peanuts to Reduce Risk of Peanut Allergy

Christopher Ling, Mercer University College of Pharmacy

Peanut allergy is one of the most common food allergies, and is represented as nearly a quarter of all allergies in children. It is suggested the allergy is least likely to be outgrown, and is associated with more severe reactions in children. [1] Due to the prevalence and severity of reaction, some recommend introducing peanut-containing products as early as four months old in those at risk of developing a peanut allergy. Moreover, if the infant has severe eczema, egg allergy, or both, specific immunoglobulin E (sIgE) measurements, skin prick test (SPT), and/or oral food challenge (OFC) are recommended before the exposure. [2] This recommendation is based on the Learning Early About Peanut Allergy (LEAP) trial results that show higher risk of peanut allergy in infants with severe eczema and/or egg allergy. [3]

In a study analyzing the data from the LEAP trial, children that consumed peanut products early had less prevalence of a peanut allergy than those that avoided peanut products in both SPT negative (1.9% vs. 13.7%; p< 0.001)  and SPT positive (10.6% vs. 35.3%; p= 0.004) groups. [4] The same authors then did a follow up study (LEAP-ON) consisting of all the eligible patients from the LEAP trial. A summary of the study is provided below. [5]

 

Effect of Avoidance on Peanut Allergy after Early Peanut Consumption
Design Randomized, follow-up study; N= 550
Objective To evaluate whether participants who had consumed peanuts in the Learning Early about Peanut Allergy (LEAP) trial would remain protected against peanut allergy after stopping peanut consumption for 12 months
Study Groups Peanut-avoidance group (n= 282)

Peanut-consumption group (n= 274)

Methods This was a follow-up to the LEAP trial where all eligible participants in the two groups of the primary trial were compared at 72 months of age. Participants were eligible for inclusion if they were a part of the intent-to treat-analysis for the primary trial.  

All participants were then asked to avoid dietary consumption of peanuts for 12 months and then re-evaluated for peanut allergy with either:

  • Oral challenge (tolerance = absence of symptoms after 5 g of peanut protein)
  • Diagnostic SPT
  • SIgE measurement
Duration May 2011 to May 2015
Primary Outcome Measure Percentage of participants with peanut allergy after 12 months of peanut-avoidance
Baseline Characteristics
Negative Stratum – Peanut Avoidance Group Negative Stratum – Peanut Consumption Group Positive Stratum – Peanut Avoidance Group Positive Stratum – Peanut Consumption Group Total
Participants 235 228 47 46 556
Age in months (standard deviation) 61.0  (3.44) 61.7  (4.19) 60.6  (3.76) 61.4  (4.98) 61.3  (3.93)
Female  85 (36.2%)   102 (44.7%)   14 (29.8%)   18 (39.1%)   219 (39.4%)
Male  150 (63.8%)   126 (55.3%)   33 (70.2%)   28 (60.9%)   337 (60.6%)

Negative stratum: Participants that had negative response to a skin prick test for peanut allergen

Positive stratum:  Participants that had positive response to a skin prick test for peanut allergen

Results Peanut allergy at month 72

Peanut-avoidance (n= 280) Peanut-consumption (n= 270) p value
Peanut allergy after 12 months of peanut-avoidance, (%) 52 (18.6%) 13 (4.8%) < 0.001

Arachis Hypogaea 2 protein (Ara h2) specific IgE:

·        Peanut-consumption group: remained low up to 72 months

·        Peanut-avoidance group: stable but significantly higher than the peanut-consumption group

·        p< 0.001

Wheal size on SPT:

·        Wheal size remained smaller in the peanut-consumption group than peanut– avoidance group at 72 months

·        p< 0.001

Adverse Events Common Adverse Events:

  • Overall (LEAP avoiders vs. LEAP consumers):
  • 252 of 282 participants [89.4%] vs. 221 of 274 [80.7%]; relative risk (RR) 1.108; p< 0.05
  • Specific ADEs with p < 0.05: eczema (RR 1.429), lower respiratory tract infection (RR 1.781), myopia (5 vs 0 events), gastroenteritis (RR 1.640) infections and infestation (RR 1.081), and immune system disorders (RR 1.590)
Serious Adverse Events: not disclosed
Percentage that Discontinued due to Adverse Events: not disclosed
Study Author Conclusions Those who had early peanut exposure during the first 60 months of life appeared to be able to maintain their “unresponsiveness” to peanut even after extended period of avoiding peanuts (12 months).  

 

This study shows that infants who had consumed peanut products in the first 60 months of their life remained unaffected to peanuts even after 12 months of avoiding peanuts. In the peanut-avoidance group, 18.6% developed peanut allergies in the following 12 months compared to 4.8% in the peanut-consumption group. Amongst the participants in the peanut-consumption group that did not develop a peanut allergy, the results (small wheal SPT, low levels of Ara h2-specific IgE, and high ratios of peanut-specific IgG4:IgE) showed that their non allergic status remained stable throughout the 12 month follow up period. One possible limitation of the study was the different rates in the overall adherence between the peanut-consumption group (90.4%) and the avoidance group (69.3%); however, the per-protocol analysis was adequately powered. Further additional studies need to be done to see if this “unresponsiveness” to peanuts continues years after the early introduction of peanuts.

 

 

References

[1] Dyer AA, Rivkina V, Perumal D, Smeltzer BM, Smith BM, Gupta RS. Epidemiology of childhood peanut allergy. Allergy Asthma Proc. 2015;36(1):58-64.

[2] Togias A, Cooper SF, Acebal ML, et al. Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. Ann Allergy Asthma Immunol. 2017;118(2):166-173.e7.

[3] Du toit G, Roberts G, Sayre PH, et al. Identifying infants at high risk of peanut allergy: the Learning Early About Peanut Allergy (LEAP) screening study. J Allergy Clin Immunol. 2013;131(1):135-43.e1-12.

[4] Toit GD, Roberts G, Sayre PH, et al. Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy. N Engl J Med. 2015;372(9):803-813.

[5] Toit GD, Sayre PH, Roberts G, et al. Effect of Avoidance on Peanut Allergy after Early Peanut Consumption. N Engl J Med. 2016;374(15):1435-43.

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