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expert reaction to study on peanut allergy oral immunotherapy and allergic reactions

Research published in The Lancet demonstrates that immunotherapy for peanut allergies increased allergic reactions.

Dr Alexandra Santos, MRC Clinician Scientist at King’s College London specialising in paediatric allergy, said:

“This is a very interesting study, which results from a systematic review and meta-analyses of 12 published randomised-controlled trials of peanut oral immunotherapy and shows that this treatment increases the risk and frequency of allergic reactions to peanut.

“Previous studies have shown that peanut oral immunotherapy induces desensitisation, reflected by an increase in the dose of allergen tolerated in the context of a supervised consumption in hospital (so-called peanut challenges) while on treatment, which is accompanied by typical immunological changes. There has been no evidence, however, that peanut oral immunotherapy enables patients to eat peanut ad libitum in the long-term and treated patients often remain peanut allergic, as evidenced by allergic reactions during peanut challenges after a period of discontinuation of treatment. In this systematic review, the frequency of allergic reactions in everyday life out of the controlled environment of a hospital setting was assessed and showed to be higher compared to standard practice of avoiding the allergen.

“Although exposure to the allergen during peanut oral immunotherapy may reportedly reduce anxiety in some patients and their families and give a sense of proactive management of their condition, differences in quality of life have not been shown in the published study. These findings raise the question as to whether peanut oral immunotherapy is protective and constitutes a disease-modifying treatment for peanut allergy.”

Dr Louisa James, British Society for Immunology spokesperson and Lecturer in Immunology at Queen Mary University of London:

“Allergic reactions can occur because the patient’s immune system produce IgE antibodies against peanut proteins, these antibodies can trigger allergic reactions when they come into contact with peanut. The aim of oral immunotherapy is to override this IgE-driven reaction by changing the way the immune system responds to peanut. The allergic reactions that occur during oral immunotherapy tend to happen during the early stages of treatment which reflects the fact that it takes several weeks or months of continuous exposure to peanut to overcome this IgE response.

“Peanut allergy affects around 1 in 50 children and has been steadily increasing in incidence over recent decades. Life threatening reactions are extremely rare but the likelihood and severity of allergic reactions to peanut are unpredictable, negatively affecting the everyday lives of patients and their carers.

“Over recent years several different research groups have carried out clinical trials to test whether oral immunotherapy could reduce or even remove the risk of allergic reactions to peanut. Peanut oral immunotherapy involves eating precise doses of peanut (usually as peanut flour) every day in increasing doses up to a ‘maintenance’ dose which typically contains the equivalent of around 4 peanuts.

“This study analysed the combined results of 12 separate randomised controlled trials of peanut oral immunotherapy in young children. Combining the results of several independent studies allows more confident evaluation of the results than looking at each study individually.  The analysis found that patients treated with oral immunotherapy were less likely to react to peanut at the end of the study but were more likely to experience allergic reactions during the treatment. Both the risk and the frequency of severe reactions was increased in patients receiving oral immunotherapy and their occurrences were unpredictable.

“The long-term effects of oral immunotherapy for peanut allergy are yet to be fully evaluated and it is unclear if the benefits of current approaches translate into a cure. Different approaches are being developed which aim to improve the safety of oral immunotherapy but these will require testing in randomised controlled trials. As highlighted by this study, tests that can accurately predict the likelihood and severity of allergic reactions to peanut are imperative.”

Dr Andrew Clark, Consultant Paediatric Allergist, Cambridge Peanut Allergy Clinic, Cambridge University Hospitals NHS Foundation Trust, said:

“We welcome the new research paper by Chu et al which contributes to the science of food oral immunotherapy. The researchers claim that the systematic review of 12 randomised controlled trials of peanut oral immunotherapy (POIT) shows an increased chance of allergic reactions when compared to just avoiding peanuts.

“Peanut allergy affects 1 in 50 children and is the commonest cause of food allergy deaths. Quality of life is reduced by fear of reactions whenever food is eaten, leading to constant worry and limitation of lifestyle.

“We at the Cambridge Group are pioneers in the POIT area having performed the world’s first published controlled trial and treated nearly 200 patients in an expanded access programme in the Cambridge Peanut Allergy Clinic.

“The risks of reacting during POIT are already well described but reduce substantially over time – a point missed in the Chu et al paper, where studies mostly followed patients during only the early phase of treatment. Reactions occur most often during up-dosing (where Chu et al focused) but are rare during long-term maintenance. Treatment offers exceptional protection against accidental ingestion of large amounts of peanut protein – shown in the study by Chu et al by a relative risk of passing an oral peanut challenge, of 12·4 [95% CI 6·82–22·61]. Controlled trials of POIT consistently show 60-70% of patients are able to tolerate doses of peanut >1000mg (approximately 10 peanuts) following treatment. For patients, achieving a negative challenge to even 300mg of protein provides a 95% reduction in the risk of accidentally reacting to peanut found in commonly consumed snacks.

“Having experience from clinical trials and our early access programme at Cambridge University Hospitals NHS Foundation Trust (CUH), we have unique insight into how patients weigh up these risks and benefits. The main burden of peanut allergy occurs in children.

“A key motivation for families is gaining protection against the effects of accidental peanut ingestion when their child becomes more independent and begins to choose their own food outside the home. Many are willing to take that risk of an allergic reaction to a medicine in a controlled environment, with a defined dose, that they have administered themselves, whilst the child is in their care, and whilst they have emergency medication available, in order to prevent uncontrolled reactions occurring to accidental ingestion.

“The paper by Chu et al presents only one part of the story of POIT. The other significant story is the substantial benefit patients gain from protection against reacting to peanut eaten without warning or control. We do agree that further research is required, and with the emergence of licensed products we expect that quality of life and health economics questions will be addressed, leading to focused use of POIT in the patients who the most to benefit from treatment.”

Dr Louisa James, British Society for Immunology spokesperson and Lecturer in Immunology at Queen Mary University of London:

“Peanut allergy affects around 1 in 50 children and has been steadily increasing in incidence over recent decades. Life threatening reactions are extremely rare but the likelihood and severity of allergic reactions to peanut are unpredictable, negatively affecting the everyday lives of patients and their carers.

“Over recent years several different research groups have carried out clinical trials to test whether oral immunotherapy could reduce or even remove the risk of allergic reactions to peanut. Peanut oral immunotherapy involves eating precise doses of peanut (usually as peanut flour) every day in increasing doses up to a ‘maintenance’ dose which typically contains the equivalent of around 4 peanuts.

“This study analysed the combined results of 12 separate randomised controlled trials of peanut oral immunotherapy in young children. Combining the results of several independent studies allows more confident evaluation of the results than looking at each study individually.  The analysis found that patients treated with oral immunotherapy were less likely to react to peanut at the end of the study but were more likely to experience allergic reactions during the treatment. Both the risk and the frequency of severe reactions was increased in patients receiving oral immunotherapy and their occurrences were unpredictable.

“The long-term effects of oral immunotherapy for peanut allergy are yet to be fully evaluated and it is unclear if the benefits of current approaches translate into a cure. Different approaches are being developed which aim to improve the safety of oral immunotherapy but these will require testing in randomised controlled trials. As highlighted by this study, tests that can accurately predict the likelihood and severity of allergic reactions to peanut are imperative.”

Dr Glenis Scadding, Consultant Physician In Allergy & Rhinology, Royal National Throat, Nose and Ear Hospital*, said:

Is this good quality research?  Are the conclusions backed up by solid data?

“Yes, but the grade of anaphylaxis is not specified. How many children needed to go to A&E or were admitted to hospital? There were no fatalities – whereas fatalities occur in those avoiding peanuts then eating them accidentally. Bigger and longer-term studies are needed.”

How does this work fit with the existing evidence? Where does this leave the desensitization theory for peanut allergy and other allergies?

“In all allergen desensitisation there is usually a period when reactions to the allergen occur before desensitization is achieved – these are controlled by gradual dose increases in the case of peanut desensitization. However, reactions are modified by other factors such as other allergens, exercise, viral infections, hormones, medication etc so a dose tolerated one time may not be the next. It is safer to have a reaction at home where it can be rapidly dealt with. In fact, having anaphylaxis and dealing with it correctly is an important lesson – it should make the subject and their family more confident at their ability to cope. All subjects/carers need rapidly available contact with the supervising doctor for advice throughout the procedure.

Other possible avenues would be the use of anti- IgE to cover the initial period of desensitization- this reduces allergic reactions.

What are the implications in the real world?

“The subjects and their families need to be fully informed about the problems with desensitization and balance these against the increased safety conferred by it (as demonstrated by the major improvement in the dose tolerated). They can then make an informed choice – which can be altered if necessary during desensitization.

“Prevention of food allergy by using emollients on all babies, avoiding soap (to reduce eczema) and early feeding of allergenic foods is a better way of reducing peanut allergy, esp in families with one sufferer.”

*Please note that Dr Scadding research area is aspirin desensitization, not peanut.

Professor George du Toit, children’s allergy consultant at Evelina London, said:

“This meta-analysis assesses the benefits and harms of oral immunotherapy to treat peanut allergy. A safe, simple and symptom-free peanut allergy treatment currently remains elusive. We therefore need to determine what degree of risk and discomfort peanut allergic patients are willing to accept and which clinical outcomes are important to patients and their families.

“Through participation in the Palisade trial, Guy’s and St Thomas’ is proud to have contributed to the evidence in this meta-analysis. This trial showed that patients taking the immunotherapy could tolerate significantly higher amounts of peanut protein – enough to protect against most accidental exposures, and that the severity of repeat peanut reactions decreased over time. The trial continues to follow up patients and it may be that the full benefits of the therapy become apparent over the longer term.”

‘Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety’ by Chu et al. was published in The Lancet at 23:30 UK time on Thursday 25 April 2019.

Declared interests

Dr Andrew Clark: “Co-founder and shareholder at Cambridge Allergy Ltd”

Dr Louisa James: “No conflict of interest to declare.”

Dr Glanis Scadding: “No relevant COI.”

None others received.

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