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Peanut immunotherapy increases allergic and anaphylactic reactions, finds review

BMJ 2019; 365 doi: (Published 25 April 2019) Cite this as: BMJ 2019;365:l1912
  1. Susan Mayor
  1. London, UK

Oral immunotherapy for peanut allergy, in which patients are exposed to gradually increasing doses of allergen over time, increases the risk of allergic and anaphylactic reactions despite inducing desensitisation, a review has found.1

“Our study synthesises all randomised clinical trials comparing peanut oral immunotherapy with no immunotherapy,” said lead author Derek Chu, from McMaster University, Hamilton, Canada.

“It shows that current peanut oral immunotherapy regimens can achieve the immunological goal of desensitisation, but that this outcome does not translate into less allergic reactions and anaphylaxis over time. Instead, the opposite occurs, with more allergic and adverse reactions with oral immunotherapy compared with avoidance or placebo.”

Peanut allergy is common, affecting 2% of children and 1% of adults in high income countries, and is a leading cause of food associated allergic reactions, anaphylaxis, and deaths. There is growing interest in peanut oral immunotherapy following clinical trials which showed that it induces desensitisation, but there had been no comprehensive review of the available evidence.

The review combined results from 12 trials of peanut oral immunotherapy, including a total of 1041 patients with peanut allergy with a median age of 8.7 years (interquartile range 5.9-11.2 years).

Results, reported in the Lancet, showed that the risk of anaphylaxis in patients given oral immunotherapy was just over three times higher than in those given no oral immunotherapy, increasing from 7.1% without immunotherapy to 22.2% with immunotherapy (risk ratio 3.12, 95% confidence interval 1.76-5.55). The researchers calculated that this gave a number needed to treat to harm of seven (3-19).

The frequency of anaphylaxis was more than doubled with oral immunotherapy compared with no immunotherapy (incidence risk ratio 2.72, 95% CI 1.57-4.72), as was epinephrine use (RR 2.21, 95% CI 1.27-3.83).

Oral immunotherapy was associated with increased serious adverse events compared with no immunotherapy (RR 1.92, 95% CI 1.00-3.66) and non-anaphylactic reactions including vomiting, angioedema, and upper respiratory tract reactions were also increased.

In terms of desensitisation, patients given oral immunotherapy were over 12 times more likely to pass a supervised challenge of exposure to peanut than those not given immunotherapy (RR 12.42, 95% CI 6.82-22.61). Quality of life showed no difference between the two groups in the small number of trials that assessed it.

“Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient important outcomes are needed,” concluded the authors of the study, which received no funding.

In an accompanying comment,2 Graham Roberts and Elizabeth Angier, from the University of Southampton, UK, said, “Although oral immunotherapy undoubtedly reduces the likelihood of reacting to peanuts in a controlled clinic setting, its overall side effect profile means that patients seem to have more allergic reactions while on therapy.”

They added, “Trading treatment related side effects at home for allergic reactions to accidental exposures out of the house (such as in social situations) might be beneficial for some patients.”

Roberts and Angier consider that the method used for the systematic review, in which studies of different design were grouped together, was a key limitation. Most trials compared oral immunotherapy with placebo but three used avoidance as the comparator and one compared oral immunotherapy with sublingual immunotherapy.

They also noted that the review showed minimal heterogeneity despite use of different preparations of peanut products and a wide range of different maintenance doses. In addition, there was no association between maintenance dose and risk of anaphylaxis.

Looking to the future, Roberts and Angier concluded, “We should not forget that we now know that the introduction of peanut products into the infant diet can prevent most cases of peanut allergy. We need to develop implementation strategies to reduce the number of patients with peanut allergy.”


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