A SLOW, low-dose peanut oral immunotherapy (OIT) regimen enabled most peanut-allergic preschool children to achieve sustained unresponsiveness after three years of treatment, according to findings from the SMACHO randomised controlled trial conducted in Sweden.
The study evaluated whether gradual up-dosing combined with a relatively low maintenance dose could improve the safety profile of peanut OIT in very young children while maintaining efficacy.
Peanut allergy affects up to 2% of children in many Western countries and is associated with a risk of severe allergic reactions and reduced quality of life. Although OIT has emerged as a promising treatment strategy, concerns remain regarding treatment-related adverse events, particularly with protocols involving rapid escalation or high maintenance doses.
SMACHO Trial Evaluates Low-Dose Peanut OIT in Toddlers
In the SMACHO trial, 75 peanut-allergic children aged 1–3 years were randomised in a 2:1 ratio to receive peanut OIT or continue peanut avoidance. Eligible participants reacted to no more than 278 mg of peanut protein during baseline food challenge testing.
Children assigned to OIT underwent dose increases every 4–6 weeks before reaching a maintenance dose of 285 mg peanut protein daily. After three years of therapy, participants completed a 4–6 week peanut-free period before repeat challenge testing.
The primary endpoint was sustained unresponsiveness, defined as tolerating at least 750 mg of peanut protein after the avoidance phase. Researchers found that 82% of treated children achieved this outcome. Before the peanut-free interval, 84% tolerated at least 750 mg, compared with just 12% in the avoidance group.
Median cumulative tolerated dose after treatment reached 5000 mg peanut protein, versus only 3 mg among children who avoided peanut throughout the study.
Safety outcomes were favourable overall. Adverse reactions occurred during 0.7% of administered doses, and most events were mild. Six children experienced eight severe dose-related reactions, including breathing difficulties, reduced general wellbeing, or anaphylaxis. Epinephrine was administered on three occasions in two children, all during the up-dosing phase.
Early Intervention May Help Reduce Peanut Allergy Burden
The investigators concluded that slow up-dosing with a low maintenance dose may offer a safer alternative to more intensive OIT protocols and could be feasible for wider clinical implementation. Combined with early dietary peanut introduction, the approach may help reduce the future burden of peanut allergy.
Reference
Klevebro S et al. Safety and efficiency of peanut oral immunotherapy in preschool children with slow up-dosing and low maintenance dosing: a randomised controlled trial. Lancet Reg Health Eur. 2026; DOI: 10.1016/j.lanepe.2026.101690.
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