Safety and Efficacy of Very Low-Dose Multi-Nut Oral Immunotherapy in Children

Background: Oral immunotherapy (OIT) is a management strategy for food allergies, typically one at a time, with maintenance doses ≥ 300 mg protein. However, 30% of allergic children have multiple trigger foods, and large maintenance doses are associated with side effects. If efficacious, Very Low-Dose OIT (VLOIT) may enhance safety in multi-OIT. Methods: Eighteen children with allergies to 2–5 nuts (tree nuts, peanuts) were enrolled (NCT03799328). Oral food challenge (OFC)-confirmed allergies to their nut mix at ≤ 444 mg protein each nut followed by initiation of an open-label mix of 4 mg protein/nut with dose increases every 2 months up to a maintenance dose of 30 mg protein/nut. After 18 months, an exit-OFC assessed allergic threshold changes, with a maximum of 2040 mg protein/nut. Efficacy was evaluated using pre-post treatment and proportional analyses (Wilcoxon signed-ranks, two-tailed Fisher's test). Results: The median age at enrollment was 5.0 years (IQR 3.13–9.62). The baseline median tolerated dose was 10 mg protein/nut (IQR 3–100 mg). Three withdrew, one did not reach the target maintenance but was invited for the exit OFC, resulting in 15/18 eligible for exit OFC. The median tolerated dose at exit OFC was 1000 mg (IQR 300–1000 mg), with a significant difference from baseline (p < 0.0001). Ten out of 15 participants tolerated the maximum dose (p < 0.0001). Intention-to-treat analysis showed that 14/18 children met pre-defined efficacy measures: tolerated 5X their baseline dose or ≥ 300 mg (p < 0.001). No patients required epinephrine during treatment. Conclusions: VLOIT led to a significant increase in the tolerated dose to multiple nuts.