Peanut immunotherapy trialled in preschool-aged children

A trial by US researchers has found that the majority of young peanut-allergic children treated with peanut immunotherapy achieved desensitisation after two and a half years of treatment, and one in five remained in remission 26 weeks after treatment ended. The results were published in The Lancet.

Peanut allergy affects 2% of children in Western countries and most remain allergic across their lifetime. The current standard of care for children with peanut allergy is dietary avoidance and access to self-injectable epinephrine, but the risk of peanut-induced anaphylaxis from accidental exposures persists, highlighting the need for safe and effective therapies.

Immunotherapy involves repeated exposure over time to gradually increasing doses of the allergen, to reduce allergic reactions. Previous studies in school-aged children and young adults have demonstrated that peanut oral immunotherapy can achieve desensitisation (an increased allergic reaction threshold while on therapy) in most participants, but success in achieving remission (lack of reactivity after discontinuing therapy over a prolonged period) has been limited.

“As a developing therapy, researchers are looking for ways to improve and prolong effects of peanut oral immunotherapy,” said Dr Stacie Jones, corresponding author on the new study, from the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital. “It has been suggested that intervening in early life when the immune system is still developing may prove more effective than intervening in later life.”

The study recruited 146 one- to three-year-olds, whose average tolerated dose of peanut protein was 25 mg at study entry, across five medical centres in the United States. 96 children were randomly assigned to peanut oral immunotherapy treatment and 50 children were randomly assigned to a placebo group. Over two and a half years, the treatment group received a daily dose of peanut protein powder that was gradually increased from 0.1 to 2000 mg (equivalent to roughly six peanuts), while the placebo group received an oat flour substitute.

At the end of treatment, desensitisation was tested by a supervised blinded food challenge to see if children could safely consume 5000 mg of peanut protein powder, equivalent to approximately 16 peanuts, without experiencing significant symptoms. To test remission, the food challenge was repeated after 26 weeks after treatment ended. The children were asked to avoid peanut consumption in between the two challenges.

The study found that 71% of children treated with peanut oral immunotherapy achieved desensitisation, compared to 2% in the placebo group. Significantly, 21% of children treated with peanut oral immunotherapy achieved remission compared to 2% in the placebo group — which provides a better indication of a lasting treatment effect than desensitisation, the researchers noted. Remission was more common the younger the child was at the start of therapy: 71% of those aged one year old, 35% of those aged two years old and 19% of those aged three years old achieved remission.

In addition, 20 children who did not achieve the threshold for remission could still tolerate 1755–3755 mg (roughly 6–12 peanuts) 26 weeks after the end of treatment. Therefore, a total of 57% of children who completed treatment could safely consume 1755–3755 mg peanuts, compared to 4% in the placebo group.

Most participants experienced at least one dosing reaction, which were predominantly mild to moderate and more frequent in peanut oral immunotherapy participants (98% peanut oral immunotherapy versus 80% placebo). The most common reactions were skin-related including hives, skin rashes, skin flushing (88% peanut oral immunotherapy group versus 58% placebo); gastrointestinal including stomach pain and itching in the mouth (78% peanut oral immunotherapy group versus 54% placebo); and respiratory including rhinitis, coughing and wheezing (75% peanut oral immunotherapy group versus 44% placebo). Epinephrine was used to treat 21 participants for 35 allergic reactions to the peanut oral immunotherapy over the daily dosing period.

The authors noted that direct comparisons between this study and other studies looking at oral peanut immunotherapy in older aged children cannot be made because lengths of treatment vary, as do the thresholds used to measure desensitisation and remission. They do note that a previous study has suggested that roughly 20% of peanut-allergic children may develop tolerance without treatment, but that study included children who were less sensitive to peanuts compared to this trial.

The authors also noted some limitations of their study. The food challenges were conducted under supervised study conditions, so they may not reflect how participants will react to consuming peanuts in real-world settings. There was a high dropout rate between the end of treatment and the remission test after 26 weeks of avoidance, which differed substantially between the placebo and treatment group and could have impacted the accuracy of the treatment efficacy results. Furthermore, 27% of children in the treatment group and 20% in the placebo group did not reach the 2000 mg maximum dose of treatment, potentially leading to an underestimation of the treatment response.

Study co-author Dr Wesley Burks, from the University of North Carolina at Chapel Hill, concluded, “The serious and unpredictable nature of food allergic reactions can be worrisome for affected children and their parents. Other than avoidance and medication to treat allergic reactions or anaphylaxis, there are no treatment options, resulting in a considerable burden on allergic children and their caregivers to avoid accidental exposure.

“Exploring safe and effective therapy options for children with peanut allergy is crucial to improving quality of life for this group of patients, particularly as most children remain allergic for their lifetime.”

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

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