Improving the management of peanut allergy in children and young people
File(s)
Author(s)
Patel, Nandinee
Type
Thesis
Abstract
BACKGROUND
Peanut allergy affects approximately 2% of UK children, with a rate of spontaneous resolution of about 20%. It is the most common cause of fatal food anaphylaxis in children in the UK. Currently there is no widely available treatment for peanut allergy in routine clinical practice. Management relies on socially restrictive allergen avoidance and the prompt administration of adrenaline to treat accidental exposures which result in anaphylaxis.
Peanut immunotherapy is a new approach to management, where allergic individuals are desensitised and thus able to tolerate exposure without clinical reaction. Clinical efficacy has been demonstrated in a number of studies, but safety concerns remain. Modified food allergens have been shown to reduce in vitro allergenicity and may therefore be more suitable for widespread use in oral immunotherapy, if efficacy can be maintained.
METHODS
This thesis involved two approaches. The first was a clinical trial of peanut desensitisation using modified peanut as a hypoallergenic allergen.
In the Boiled Oral Peanut Immunotherapy (BOPI) study, 47 children with peanut allergy (confirmed by double-blind, placebo-controlled food challenge (DBPCFC)) were randomised (2:1) to receive either oral immunotherapy with boiled peanut or standard allergy management (allergen avoidance). Participants underwent repeat DBPCFC at 12 months to assess response, following which peanut oral immunotherapy (OIT) was stopped, and sustained unresponsiveness (SU) assessed after 4 weeks OFF-OIT.
The second approach was to evaluate the rate of anaphylaxis responding to a single dose of intramuscular adrenaline, through a systematic review and meta-analysis of published literature. To better understand the factors why some reactions may need more than a single dose for resolution, a randomised, crossover phase IV pilot study was undertaken to compare the pharmacokinetic and pharmacodynamic effects of intramuscular adrenaline (at 2 different doses, using different devices) in 12 young people at risk of food-induced anaphylaxis.
RESULTS
Boiled peanut-OIT resulted in efficacy of 75% (by intention-to-treat analysis) as determined by tolerance at DBPCFC to 1.443g (~6 roasted peanuts) after 12 months of OIT, compared to 0% in the control group. Fifty one percent of participants achieved SU (per-protocol). Only 0.2% of OIT doses resulted in anaphylaxis. A statistically significant improvement in health-related quality of life was reported in participants and parents within the first year of OIT.
In evaluating the rate of anaphylaxis responding to a single dose of adrenaline, in a meta-analysis of 86 studies (36,557 anaphylaxis events), 7.7% (95% CI 6.4-9.1%) of all-cause anaphylaxis were treated with more than a single dose of adrenaline. When assessing only adrenaline-treated reactions due to food where a second dose was administered by a healthcare professional, 11.1% (95%CI 9.4-13.2%) of reactions required at least one further dose of adrenaline. The pilot study of pharmacokinetics/ pharmacodynamics of intramuscular adrenaline demonstrated that injection of 500mcg adrenaline resulted in a more favourable plasma adrenaline profile compared to 300mcg, with no difference in adverse events. However, clear differences in pharmacodynamics were seen between the two devices tested.
CONCLUSIONS
OIT using boiled peanut is pragmatic and effective after 1 year of treatment, with a favourable safety profile. These results justify a head-to-head comparison of OIT using roasted versus boiled peanut in a randomised control trial.
Around 10% of anaphylaxis reactions do not resolve to a single adrenaline dose, which potentially justifies current guidance from multiple regulators for individuals at risk of anaphylaxis to carry two adrenaline autoinjectors at all times. More work is needed to understand the differences in effect between different autoinjector devices, to support future guidelines.
Peanut allergy affects approximately 2% of UK children, with a rate of spontaneous resolution of about 20%. It is the most common cause of fatal food anaphylaxis in children in the UK. Currently there is no widely available treatment for peanut allergy in routine clinical practice. Management relies on socially restrictive allergen avoidance and the prompt administration of adrenaline to treat accidental exposures which result in anaphylaxis.
Peanut immunotherapy is a new approach to management, where allergic individuals are desensitised and thus able to tolerate exposure without clinical reaction. Clinical efficacy has been demonstrated in a number of studies, but safety concerns remain. Modified food allergens have been shown to reduce in vitro allergenicity and may therefore be more suitable for widespread use in oral immunotherapy, if efficacy can be maintained.
METHODS
This thesis involved two approaches. The first was a clinical trial of peanut desensitisation using modified peanut as a hypoallergenic allergen.
In the Boiled Oral Peanut Immunotherapy (BOPI) study, 47 children with peanut allergy (confirmed by double-blind, placebo-controlled food challenge (DBPCFC)) were randomised (2:1) to receive either oral immunotherapy with boiled peanut or standard allergy management (allergen avoidance). Participants underwent repeat DBPCFC at 12 months to assess response, following which peanut oral immunotherapy (OIT) was stopped, and sustained unresponsiveness (SU) assessed after 4 weeks OFF-OIT.
The second approach was to evaluate the rate of anaphylaxis responding to a single dose of intramuscular adrenaline, through a systematic review and meta-analysis of published literature. To better understand the factors why some reactions may need more than a single dose for resolution, a randomised, crossover phase IV pilot study was undertaken to compare the pharmacokinetic and pharmacodynamic effects of intramuscular adrenaline (at 2 different doses, using different devices) in 12 young people at risk of food-induced anaphylaxis.
RESULTS
Boiled peanut-OIT resulted in efficacy of 75% (by intention-to-treat analysis) as determined by tolerance at DBPCFC to 1.443g (~6 roasted peanuts) after 12 months of OIT, compared to 0% in the control group. Fifty one percent of participants achieved SU (per-protocol). Only 0.2% of OIT doses resulted in anaphylaxis. A statistically significant improvement in health-related quality of life was reported in participants and parents within the first year of OIT.
In evaluating the rate of anaphylaxis responding to a single dose of adrenaline, in a meta-analysis of 86 studies (36,557 anaphylaxis events), 7.7% (95% CI 6.4-9.1%) of all-cause anaphylaxis were treated with more than a single dose of adrenaline. When assessing only adrenaline-treated reactions due to food where a second dose was administered by a healthcare professional, 11.1% (95%CI 9.4-13.2%) of reactions required at least one further dose of adrenaline. The pilot study of pharmacokinetics/ pharmacodynamics of intramuscular adrenaline demonstrated that injection of 500mcg adrenaline resulted in a more favourable plasma adrenaline profile compared to 300mcg, with no difference in adverse events. However, clear differences in pharmacodynamics were seen between the two devices tested.
CONCLUSIONS
OIT using boiled peanut is pragmatic and effective after 1 year of treatment, with a favourable safety profile. These results justify a head-to-head comparison of OIT using roasted versus boiled peanut in a randomised control trial.
Around 10% of anaphylaxis reactions do not resolve to a single adrenaline dose, which potentially justifies current guidance from multiple regulators for individuals at risk of anaphylaxis to carry two adrenaline autoinjectors at all times. More work is needed to understand the differences in effect between different autoinjector devices, to support future guidelines.
Version
Open Access
Date Issued
2022-02-01
Date Awarded
2023-02-11
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Turner, Paul
Sponsor
National Institute for Health Research (Great Britain)
Imperial College London
Grant Number
MR/K010468/1
Publisher Department
National Heart and Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)