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: We sought 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 to 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/d in a double-blinded fashion. The primary end point, sustained unresponsiveness at 4 weeks after stopping early intervention oral immunotherapy (4-SU), was assessed by double-blinded, placebo-controlled food challenge either upon achieving 4 prespecified criteria, or after 3 maintenance years. Peanut-specific immune responses were serially analyzed. Outcomes were compared with 154 matched standard-care controls.

Results: Of 40 consented subjects, 3 (7.5%) did not qualify. Overall, 29 of 37 (78%) in the intent-to-treat analysis achieved 4-SU (300-mg arm, 17 of 20 [85%]; 3000 mg, 12 of 17 [71%], P = .43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29 of 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 IgE levels significantly increased (relative risk, 19.42; 95% CI, 8.7-43.7; P < .001). Allergic side effects during E-OIT were common but all were mild to moderate.

Conclusions: 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.

Keywords: Oral immunotherapy; desensitization; early intervention; peanut allergy; randomized clinical trial; sustained unresponsiveness.

Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Progression of subjects through the study. DBPCFC, double-blinded, placebo-controlled food challenge; EoE, eosinophilic esophagitis; OFC, oral food challenge; SU, sustained unresponsiveness.

Figure 2

Outcomes of E-OIT and standard-care treatment. (A) Clinical outcomes of E-OIT. The proportion of overall subjects, and those in each treatment arm, achieving sustained unresponsiveness are shown for both intent-to-treat and per-protocol analyses.(B) The distributions of peanut-specific IgE among E-OIT participants and matched controls practicing allergen avoidance at baseline and end-of study periods (median 29 and 43 months, respectively). Note all peanut-specific IgE levels > 100 were transformed to 101 for these analyses because dilutional analysis was not available for all high-titer samples. (C) The proportions of E-OIT and control participants able to reintroduce peanut-containing foods in the diet at the end of study period. (D) The imputed proportions able to reintroduce peanut-containing foods in the diet with evidence-based worst-case assumptions.

Figure 2

Outcomes of E-OIT and standard-care treatment. (A) Clinical outcomes of E-OIT. The proportion of overall subjects, and those in each treatment arm, achieving sustained unresponsiveness are shown for both intent-to-treat and per-protocol analyses.(B) The distributions of peanut-specific IgE among E-OIT participants and matched controls practicing allergen avoidance at baseline and end-of study periods (median 29 and 43 months, respectively). Note all peanut-specific IgE levels > 100 were transformed to 101 for these analyses because dilutional analysis was not available for all high-titer samples. (C) The proportions of E-OIT and control participants able to reintroduce peanut-containing foods in the diet at the end of study period. (D) The imputed proportions able to reintroduce peanut-containing foods in the diet with evidence-based worst-case assumptions.

Figure 2

Outcomes of E-OIT and standard-care treatment. (A) Clinical outcomes of E-OIT. The proportion of overall subjects, and those in each treatment arm, achieving sustained unresponsiveness are shown for both intent-to-treat and per-protocol analyses.(B) The distributions of peanut-specific IgE among E-OIT participants and matched controls practicing allergen avoidance at baseline and end-of study periods (median 29 and 43 months, respectively). Note all peanut-specific IgE levels > 100 were transformed to 101 for these analyses because dilutional analysis was not available for all high-titer samples. (C) The proportions of E-OIT and control participants able to reintroduce peanut-containing foods in the diet at the end of study period. (D) The imputed proportions able to reintroduce peanut-containing foods in the diet with evidence-based worst-case assumptions.

Figure 2

Outcomes of E-OIT and standard-care treatment. (A) Clinical outcomes of E-OIT. The proportion of overall subjects, and those in each treatment arm, achieving sustained unresponsiveness are shown for both intent-to-treat and per-protocol analyses.(B) The distributions of peanut-specific IgE among E-OIT participants and matched controls practicing allergen avoidance at baseline and end-of study periods (median 29 and 43 months, respectively). Note all peanut-specific IgE levels > 100 were transformed to 101 for these analyses because dilutional analysis was not available for all high-titer samples. (C) The proportions of E-OIT and control participants able to reintroduce peanut-containing foods in the diet at the end of study period. (D) The imputed proportions able to reintroduce peanut-containing foods in the diet with evidence-based worst-case assumptions.

Figure 3

Association of baseline peanut-specific IgE characteristics and outcomes. (A) Both the baseline peanut-specific IgE, and the ratio of peanut-specific to total IgE, are significantly lower among successes than failures in the ITT population. (B) Length of treatment broken down by tertiles of baseline peanut-specific IgE. Significance testing by one-way ANOVA.

Figure 3

Association of baseline peanut-specific IgE characteristics and outcomes. (A) Both the baseline peanut-specific IgE, and the ratio of peanut-specific to total IgE, are significantly lower among successes than failures in the ITT population. (B) Length of treatment broken down by tertiles of baseline peanut-specific IgE. Significance testing by one-way ANOVA.

Figure 4

Immunoregulation during E-OIT at both doses tested. Log-transformed peanut-specific IgE (A) and IgG4 (B), and raw data for mean wheal diameter of peanut skin tests (C) are plotted separately by group, with data from individuals connected by colored lines and the fitted time trajectory curve displayed with the raw data for these models. P-values comparing the parameter estimates for the two groups for each outcome are also provided.

Figure 4

Immunoregulation during E-OIT at both doses tested. Log-transformed peanut-specific IgE (A) and IgG4 (B), and raw data for mean wheal diameter of peanut skin tests (C) are plotted separately by group, with data from individuals connected by colored lines and the fitted time trajectory curve displayed with the raw data for these models. P-values comparing the parameter estimates for the two groups for each outcome are also provided.

Figure 4

Immunoregulation during E-OIT at both doses tested. Log-transformed peanut-specific IgE (A) and IgG4 (B), and raw data for mean wheal diameter of peanut skin tests (C) are plotted separately by group, with data from individuals connected by colored lines and the fitted time trajectory curve displayed with the raw data for these models. P-values comparing the parameter estimates for the two groups for each outcome are also provided.