Peanut immunotherapy may be increasing allergic reactions

Despite effectively inducing desensitisation in the clinic, oral immunotherapy for peanut allergies appears to considerably increase allergic and anaphylactic reactions, compared with avoidance or placebo.

That’s according to a systematic review including 12 studies and more than 1000 patients, published in The Lancet. The findings of the review thus highlight the gap between outcomes measured in the clinic and the allergy relief outcomes that patients desire.

Food allergy is a growing global problem, with peanut allergies affecting 2% of children and 1% of adults in high-income countries. There is no treatment for allergies, other than avoidance and medication to treat allergic reactions or anaphylaxis.

Immunotherapy is an investigational therapy for allergies that involves repeated exposure over time to gradually increasing doses of the allergen, with the aim of reducing allergic reactions. Studies of oral immunotherapy currently measure treatment success by whether a treated patient can pass a supervised food challenge, but this cannot predict a patient’s future risk and frequency of allergic reactions in the real world.

“Numerous studies of varying quality have been published on oral immunotherapy, but its effectiveness and reliability remains unclear,” said lead author Dr Derek Chu, from McMaster University.

Dr Chu and his co-authors combined results from 12 randomised controlled trials from the USA, UK, Europe and Australia (including three unpublished trials) including 1041 patients to compare outcomes after oral immunotherapy with those after no oral immunotherapy. The trials compared oral immunotherapy against placebo, avoidance or other types of immunotherapy, and used different peanut products and doses.

The average age of participants in the studies was around nine years of age, and participants were followed for a year on average. The study measured anaphylaxis (data for this was available in nine trials), allergic or adverse reactions (10 trials), epinephrine use (nine trials) and quality of life (three trials).

The results suggest that, compared with no oral immunotherapy, peanut oral immunotherapy increases the risk and frequency of anaphylaxis (by around three times, from 7.1% without oral immunotherapy to 22.2% with oral immunotherapy), epinephrine use (by around two times, from 3.7% without to 8.2% with) and serious adverse events (by around two times, from 6.2% without to 11.9% with) to a similar extent during build-up and maintenance. Allergic reactions involving the gastrointestinal tract (vomiting, abdominal pain, mouth itching), skin and mucous membranes (hives or urticaria and swelling or angioedema), nose (congestion or rhinitis) and lungs (wheeze or asthma) also increased.

“Our study … shows that current peanut oral immunotherapy regimens can achieve the immunological goal of desensitisation, but that this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis over time,” said Dr Chu. “Instead, the opposite outcome occurs, with more allergic and adverse reactions with oral immunotherapy compared with avoidance or placebo.”

The researchers did find that quality of life was no better in people receiving oral immunotherapy compared to those that did not. The authors note that this is in contrast to observational studies, and this may be due to those studies not being controlled for confounding and bias. They note that large, well-done randomised controlled trials are required to clarify the effect, if any, of peanut oral immunotherapy on quality of life.

The authors conclude that their findings favour avoidance over current forms of oral immunotherapy if a patient wishes to avoid peanut-induced anaphylaxis and allergic reactions, and that the increased risk of reactions associated with these regimens might be a substantial barrier to widespread adoption by patients with peanut allergies. They say that in future research, it will be important to clarify patient values and preferences regarding food allergy therapies in general — understanding what patients expect from treatment, and what outcomes are desirable and undesirable.

“Our results do not denounce current research in oral immunotherapy, but the method needs to be more carefully considered, improvements in safety made and measures of success need to be aligned with patients’ wishes,” said Dr Chu.

Writing in a linked Comment, Graham Roberts and Elizabeth Angier from the University of Southampton noted that it might be useful to compare oral with epicutaneous immunotherapy.

“Although epicutaneous immunotherapy is less effective, it has a better safety profile than oral immunotherapy, which some patients might find more acceptable,” they wrote. “Finally, we should not forget that we now know that the early introduction of peanut products into the infant diet can prevent most cases of peanut allergy. Moving forward we need to develop implementation strategies to reduce the number of patients with peanut allergy.”

Image credit: ©stock.adobe.com/au/glisic_albina

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