Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective

Abstract

Background Oral immunotherapy (OIT) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted. Newly-diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment. Objective To test the safety, effectiveness, and feasibility of early OIT (E-OIT) in the treatment of peanut allergy. Methods We enrolled 40 children aged 9–36 months with suspected or known peanut allergy. Qualifying subjects reacted to peanut during an entry food challenge and were block-randomized 1:1 to receive E-OIT at goal maintenance doses of 300 or 3000 mg/day in a double-blinded fashion. The primary endpoint, sustained unresponsiveness at four weeks after stopping E-OIT (4-SU), was assessed by DBPCFC either upon achieving four pre-specified criteria, or after three maintenance years. Peanut-specific immune responses were serially analyzed. Outcomes were compared to 154 matched standard-care controls. Results Of 40 consented subjects, three (7.5%) did not qualify. Overall, 29/37 (78%) in the intent-to-treat analysis achieved 4-SU (300 mg arm, 17/20 [85%]; 3000 mg, 12/17 [71%], p=0.43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29/32 (91%). Peanut-specific IgE levels significantly declined in E-OIT-treated children, who were 19 times more likely to successfully consume dietary peanut than matched standard-care controls, in whom peanut-specific IgEs significantly increased (RR 19.42 [95%CI 8.7 – 43.7], p<0.001). Allergic side effects during E-OIT were common but all were mild-moderate. Conclusion At both doses tested, E-OIT had an acceptable safety profile and was highly successful in rapidly suppressing allergic immune responses and achieving safe dietary reintroduction.

Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy

“…3), which likely corresponds to the reduction of the numbers of IgEproducing cells. This result was concordant with the results based on serum peanut-specific IgE levels (P = 0.034 and 0.62, respectively, in OIT and placebo groups), and also several reports demonstrating that serum peanut-specific IgE levels were significantly decreased by the treatment of OIT [13,21,24,25]. We observed one common IGHE clone among two pre-treated OIT and five pre-treated placebo samples (Supplementary Table 5), but this clone was still retained in the samples after OIT and placebo treatment.…”

“…Among them, 12 patients received peanut flour and the remaining 5 patients received a placebo until the final oral food challenges. In this analysis, we focused on IGHA, IGHE, and IGHG, which have been reported to associate with food allergy [13,[21][22][23][24][25]. In the expression analysis using real-time qPCR, we observed the tendency of Table 1 Mapping pattern of BCR reads in a healthy donor Number of reads (%) -not mapped decrease of IGHE expression after OIT compared to before OIT (P = 0.052) but not in placebo group (P = 0.63) (Fig.…”

Low-Dose Oral Immunotherapy Using Low-Egg-Allergen Cookies for Severe Egg-Allergic Children Reduces Allergy Severity and Affects Allergen-Specific Antibodies in Serum

“…Although egg OIT generally uses EW powder [2][3][4], Yanagida et al [8] reported that low-dose (i.e., 1/100-1/32 of a whole egg [62-192 mg of egg protein] in scrambled form once a day) OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg in scrambled form, with no severe symptoms. Vickery et al [11] reported that sustained unresponsiveness was achieved at high rates with OIT, both low-dose (300 mg) and high-dose (3,000 mg) peanut flour once a day, in young peanut-allergic children. However, in an allergic mouse model, the intake of a small amount of allergen did not induce oral desensitization [12].…”

Oral Immunotherapy for Food Allergy

“…In a more recent open-label RCT analyzing peanut OIT in a population aged 9 to 36 months [25], patients were randomized to goal maintenance doses of 300 mg/d or 3000 mg/d. In the intentto-treat analysis, 29 of 37 patients (78%) achieved SU 4 weeks after completing treatment, with similar rates in the 300-mg group (85%) and the 3000-mg group (71%) after a median treatment period of 29 months.…”