Safety and efficiency of peanut oral immunotherapy in preschool children with slow up-dosing and low maintenance dosing: a randomised controlled trial.

Background: Oral immunotherapy (OIT) is an emerging treatment for peanut allergy. A variety of protocols have been investigated, and accumulating evidence suggests that younger children may benefit from greater immune plasticity. The aim of the Small Children Oral Immunotherapy (SMACHO) study was to investigate the efficacy and safety of 3 years of peanut OIT with slow up-dosing and a low maintenance dose followed by 4-6 weeks of peanut-free diet in peanut-allergic toddlers. Methods: SMACHO is an open-labelled randomised controlled trial in Stockholm, Sweden (NCT04511494). After a positive peanut challenge to a cumulative dose of maximum 278 mg peanut protein, 75 allergic children, aged 1-3 years, were randomised 2:1 to peanut OIT, with slow up-dosing every 4-6 weeks and a low maintenance dose of 285 mg peanut protein, or to avoidance. Primary outcome was the proportion of children achieving sustained unresponsiveness, defined as tolerating a cumulative dose of ≥750 mg peanut protein in a challenge after 3 years of OIT followed by 4-6 weeks of a peanut-free diet. Findings: After OIT, 82% (41 of 50) achieved sustained unresponsiveness to a cumulative dose of ≥750 mg peanut protein. Before the peanut-free period, 84% (42 of 50) tolerated ≥750 mg peanut protein, compared with 3 of 25 children (12%) without treatment: difference 72% (95% confidence interval (CI) 56-88), p < 0·0001. Median cumulative tolerated dose after treatment was 5000 mg peanut protein compared with 3 mg after 3 years of peanut avoidance: difference 4997 mg (95% CI 4867-5127), p < 0·0001. Adverse events occurred in 0·7% of administered peanut doses, and most were mild. Six children reported eight severe dose-related events, with affected breathing, affected general well-being, or anaphylaxis. Epinephrine was administered at home three times in two children for dose-related reactions, all during up-dosing. Interpretation: Peanut OIT for young children, using slow up-dosing and a low maintenance dose, may be safer than protocols that escalate more rapidly or involve a higher maintenance dose. Our protocol can be implemented in clinical practice. When combined with early dietary introduction of peanut; this strategy has potential to contribute to a future decline in the prevalence of peanut allergy. Funding: This work was supported by a private non-commercial donation through Karolinska Institutet. Additionally by the Swedish Asthma and Allergy Association's Research Foundation; the Ellen, Walter and Lennart Hesselman Foundation for Scientific Research; Karolinska Institutet; Region Stockholm (ALF (FoUI-961605 and FoUI-973325) and clinical research appointments for Asarnoj, Nilsson, Konradsen and Klevebro); HRH Crown Princess Lovisa's association for child healthcare; the Samariten foundation for paediatric research; the Swedish Association for Allergology; the Freemasons of Sweden; the Swedish Society of Medicine; the Swedish Paediatric Society's Section for Allergy and Asthma, the Swedish Research Council (Dnr 2020-01839; 2023-02616); the Cancer and Allergy Foundation; the association Mjölkdroppen in Sweden; the Golden Jubilee Memorial Foundation; the Magnus Bergvall Foundation.