Scientific Study

Background: Studies are limited on the efficacy of peanut sublingual immunotherapy (SLIT). The durability of desensitization after SLIT has not been well described. Objective: To evaluate the efficacy and safety of 4 mg peanut SLIT and persistence of desensitization after SLIT discontinuation. Methods: Challenge proven peanut-allergic 1-11 year old children were treated with open-label 4 mg peanut SLIT for 48 months. Desensitization after peanut SLIT was assessed by 5000 mg double-blind, placebo-controlled food challenge (DBPCFC). A novel randomly assigned avoidance period between 1-17 weeks was followed by a DBPCFC. Skin prick testing (SPT), immunoglobulins, basophil activation testing (BAT), T_H1, T_H2, and IL-10 cytokines were measured longitudinally. Safety was assessed through patient-reported home diaries. Results: Fifty-four participants were enrolled and 47 (87%) completed peanut SLIT and the 48-month DBPCFC per protocol. Mean successfully consumed dose (SCD) during DBPCFC increased from 48 mg to 2723 mg peanut protein after SLIT (p<0.0001), with 70% achieving clinically significant desensitization (SCD >800 mg) and 36% full desensitization (SCD = 5000 mg). Modeled median time to loss of clinically significant desensitization was 22 weeks. Peanut SPT; peanut-specific IgE, IgG4, IgG4/IgE ratio; and peanut-stimulated BAT, IL-4, IL-5, IL-13, IFN-gamma, and IL-10 changed significantly compared to baseline with changes seen as early as 6 months. Median rate of reaction per dose was 0.5% with transient oropharyngeal itching most common and no dosing symptoms requiring epinephrine. Conclusion: In this open-label, prospective study, peanut SLIT was safe and induced clinically significant desensitization in the majority of children lasting more than 17 weeks after discontinuation of therapy. https://doi.org/10.1016/j.jaci.2023.01.036