Cochrane Database of Systematic Reviews

Allergen-specific oral immunotherapy for peanut allergy

(Review)

Nurmatov U, Venderbosch I, Devereux G, Simons FER, Sheikh A

Nurmatov U, Venderbosch I, Devereux G, Simons FER, Sheikh A.

Allergen-specific oral immunotherapy for peanut allergy.
Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD009014.
DOI: 10.1002/14651858.CD009014.pub2.

www.cochranelibrary.com

Allergen-specific oral immunotherapy for peanut allergy (Review)

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]

Allergen-specific oral immunotherapy for peanut allergy

Ulugbek Nurmatov1 , Iris Venderbosch2 , Graham Devereux3 , F Estelle R Simons4 , Aziz Sheikh5

1 Allergy& Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK.
2 Radboud University Nijmegen Medical Center, Nijmegen, Netherlands. 3 Department of Child Health, Royal Aberdeen Children’s
Hospital, The University of Aberdeen, Aberdeen, UK. 4 Department of Pediatrics & Child Health; Department of Immunology, Faculty
of Medicine, University of Manitoba, Winnipeg, Canada. 5 Centre for Population Health Sciences, The University of Edinburgh,
Edinburgh, UK

Contact address: Aziz Sheikh, Centre for Population Health Sciences, The University of Edinburgh, Medical School, Doorway 3,
Teviot Place, Edinburgh, EH8 9AG, UK. Aziz.Sheikh@ed.ac.uk.

Editorial group: Cochrane Tobacco Addiction Group.

Publication status and date: New, published in Issue 9, 2012.

Citation: Nurmatov U, Venderbosch I, Devereux G, Simons FER, Sheikh A. Allergen-specific oral immunotherapy for peanut allergy.
Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD009014. DOI: 10.1002/14651858.CD009014.pub2.

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

Background

Peanut allergy is one of the most common forms of food allergy encountered in clinical practice. In most cases, it does not spontaneously
resolve; furthermore, it is frequently implicated in acute life-threatening reactions. The current management of peanut allergy centres
on meticulous avoidance of peanuts and peanut-containing foods. Allergen-specific oral immunotherapy (OIT) for peanut allergy
aims to induce desensitisation and then tolerance to peanut, and has the potential to revolutionise the management of peanut allergy.
However, at present there is still considerable uncertainty about the effectiveness and safety of this approach.

Objectives

To establish the effectiveness and safety of OIT in people with IgE-mediated peanut allergy who develop symptoms after peanut
ingestion.

Search methods

We searched in the following databases: AMED, BIOSIS, CAB, CINAHL, The Cochrane Library, EMBASE, Global Health, Google
Scholar, IndMed, ISI Web of Science, LILACS, MEDLINE, PakMediNet and TRIP. We also searched registers of on-going and
unpublished trials. The date of the most recent search was January 2012.

Selection criteria

Randomised controlled trials (RCTs), quasi-RCTs or controlled clinical trials involving children or adults with clinical features indicative
of IgE-mediated peanut allergy treated with allergen-specific OIT, compared with control group receiving either placebo or no treatment,
were eligible for inclusion.

Data collection and analysis

Two review authors independently checked and reviewed titles and abstracts of identified studies and assessed risk of bias. The full text
of potentially relevant trials was assessed. Data extraction was independently performed by two reviewers with disagreements resolved
through discussion.
Allergen-specific oral immunotherapy for peanut allergy (Review)
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Main results
We found one small RCT, judged to be at low risk of bias, that enrolled 28 children aged 1 to 16 years with evidence of sensitisation
to peanut and a clinical history of reaction to peanut within 60 minutes of exposure. The study did not include children who had
moderate to severe asthma or who had a history of severe peanut anaphylaxis. Randomisation was in a 2:1 ratio resulting in 19 children
being randomised to the intervention arm and nine to the placebo arm. Intervention arm children received OIT with peanut flour and
control arm participants received placebo comprising of oat flour. The primary outcome was assessed using a double-blind, placebo
controlled oral food challenge (OFC) at approximately one year. No data were available on longer term outcomes beyond the OFC
conducted at the end of the study.
Because of adverse events, three patients withdrew from the intervention arm before the completion of the study. Therefore, only 16
participants received the full course of peanut OIT, whereas all nine patients receiving placebo completed the trial. The per-protocol
analysis found a significant increase in the threshold dose of peanut allergen required to trigger a reaction in those in the intervention
arm with all 16 participants able to ingest the maximum cumulative dose of 5000 mg of peanut protein (which the authors equate as
being equivalent to approximately 20 peanuts) without developing symptoms, whereas in the placebo group they were able to ingest
a median cumulative dose of 280 mg (range: 0 to 1900 mg, P < 0.001) before experiencing symptoms. Per-protocol analyses also
demonstrated that peanut OIT resulted in reductions in skin prick test size (P < 0.001), interleukin-5 (P = 0.01), interleukin-13 (P =
0.02) and an increase in peanut-specific immunoglobulin G4 (IgG4 ) (P < 0.01).
Children in the intervention arm experienced more adverse events during treatment than those in the placebo arm. In the initial day
escalation phase, nine (47%) of the 19 participants initially enrolled in the OIT arm experienced clinically-relevant adverse events
which required treatment with H1 -antihistamines, two of which required additional treatment with epinephrine (adrenaline).
Authors’ conclusions
The one small RCT we found showed that allergen-specific peanut OIT can result in desensitisation in children, and that this is
associated with evidence of underlying immune-modulation. However, this treatment approach was associated with a substantial risk
of adverse events, although the majority of these were mild. In view of the risk of adverse events and the lack of evidence of long-
term benefits, allergen-specific peanut OIT cannot currently be recommended as a treatment for the management of patients with IgE-
mediated peanut allergy. Larger RCTs are needed to investigate the acceptability, long-term effectiveness and cost-effectiveness of safer
treatment regimens, particularly in relation to the induction of clinical and immunological tolerance.

PLAIN LANGUAGE SUMMARY

Oral immunotherapy for the treatment of peanut allergy
Allergy to peanut can result in potentially life-threatening reactions and, on occasions, death. Unlike many other forms of food allergy,
allergy to peanut is typically life-long. There is currently no cure for peanut allergy and people with this allergy must constantly be
careful to avoid accidentally eating peanut or peanut-containing foods. If a person with a peanut allergy accidentally ingests peanut,
he or she may develop serious allergic reactions necessitating emergency treatment with epinephrine (adrenaline).
The overall goal of allergen-specific oral immunotherapy (OIT) for peanut allergy is to reduce and, if possible, eliminate the risk
of further reactions associated with exposure to peanuts. Most people who have reactions to peanut have an immediate type (also
sometimes known as IgE-mediated) reaction in which symptoms typically develop within minutes of exposure to peanut protein and
it is for this group that allergen-specific OIT is a potential treatment approach. It is not considered suitable for those who experience
more delayed (also sometimes known as non-IgE mediated) reactions. Treatment involves giving people with peanut allergy very small
doses of peanut protein by mouth and gradually increasing the amount being administered (the build-up phase). Once the desired
dose has been achieved, this is followed by the patient taking the same dose of peanut every day for a set period of time (maintenance
phase). As giving doses of peanut to someone with a peanut allergy has the potential to introduce allergic reactions, participants’ safety
needs to be carefully monitored during studies of peanut OIT.
We found one small trial undertaken in 28 children aged 1 to 16 years with confirmed peanut allergy. The study did not include children
who had moderate to severe asthma or who had had severe anaphylaxis (a severe allergic reaction that may result in death) because
of their peanut allergy. The authors randomised children to intervention or placebo in a 2:1 ratio. Intervention arm children received
peanut flour whereas control arm participants received oat flour. The 48-week trial showed that treatment with peanut OIT enabled
children receiving OIT to substantially increase the amount of peanut flour they ate in comparison with those in the placebo arm
Allergen-specific oral immunotherapy for peanut allergy (Review)
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
without having an allergic reaction. However, almost half of the children (nine out of 19) receiving OIT had an allergic reaction due to
the OIT which required antihistamines, and two had more serious reactions to the treatment which required adrenaline (epinephrine).
Although promising, based on the findings of this one small trial, we cannot recommend that peanut OIT be used routinely for
people with peanut allergy. There is a need for further larger studies investigating safer OIT regimens and establishing the long-term
effectiveness of OIT after treatment is stopped.

Allergen-specific oral immunotherapy for peanut allergy (Review)

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.