A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response

Abstract

Background: Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.

Objective: To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind, placebo-controlled study.

Methods: In this multicenter study, children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge (OFC) at approximately 1 year. Titrated skin prick tests (SPTs) and laboratory studies were performed at regular intervals.

Results: Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study because of allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (n = 16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), whereas placebo subjects (n = 9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg; P < .001). In contrast with the placebo group, the peanut OIT group showed reductions in SPT size (P < .001), IL-5 (P = .01), and IL-13 (P = .02) and increases in peanut-specific IgG(4) (P < .001). Peanut OIT subjects had initial increases in peanut-specific IgE (P < .01) but did not show significant change from baseline by the time of OFC. The ratio of forkhead box protein 3 (FoxP3)(hi): FoxP3(intermediate) CD4+ CD25+ T cells increased at the time of OFC (P = .04) in peanut OIT subjects.

Conclusion: These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance.

Figure 1. Cumulative amount of peanut protein ingested at OFC by peanut OIT and placebo subjects (*p<0.001) following 12 months of therapy

Individual subjects are shown as diamonds (peanut OIT) or squares (placebo); lines designate median values.

Figure 2. Titrated skin prick testing

Change in median wheal size from baseline to time of OFC in peanut OIT and placebo subjects (*p<0·001). Boxes represent 25-75% quartiles; whiskers represent range. Lines designate median values.

Figure 3. Changes in serum immunoglobulin levels during treatment with peanut OIT and placebo

(a) Peanut-specific IgE. (*p≤0.01). (b) Peanut-specific IgG. (*p<0.05). (c) Peanut-specific IgG₄. (*p≤0.001). Boxes represent 25-75% quartiles; whiskers represent range. Lines designate median values.

Figure 3. Changes in serum immunoglobulin levels during treatment with peanut OIT and placebo

(a) Peanut-specific IgE. (*p≤0.01). (b) Peanut-specific IgG. (*p<0.05). (c) Peanut-specific IgG₄. (*p≤0.001). Boxes represent 25-75% quartiles; whiskers represent range. Lines designate median values.

Figure 3. Changes in serum immunoglobulin levels during treatment with peanut OIT and placebo

(a) Peanut-specific IgE. (*p≤0.01). (b) Peanut-specific IgG. (*p<0.05). (c) Peanut-specific IgG₄. (*p≤0.001). Boxes represent 25-75% quartiles; whiskers represent range. Lines designate median values.

Figure 4. Changes in secreted cytokine responses for subjects receiving peanut OIT and placebo

PBMCs were cultured with peanut protein for 72 hours; cytokines were measured via ELISA. (a) IL-5. (*p≤0·02). (b) IL-13. (*p≤0·03).

Figure 4. Changes in secreted cytokine responses for subjects receiving peanut OIT and placebo

PBMCs were cultured with peanut protein for 72 hours; cytokines were measured via ELISA. (a) IL-5. (*p≤0·02). (b) IL-13. (*p≤0·03).

Figure 5. Change in FoxP3 ^hi: FoxP3 ^intermediate CD4+CD25+ T cells from baseline to time of OFC

PBMCs were stimulated with crude peanut extract and tetanus toxin for 7 days, and then stained for Treg markers. Individual subjects are shown for (a) peanut OIT and (b) placebo groups. *p=0.04.

Figure 5. Change in FoxP3 ^hi: FoxP3 ^intermediate CD4+CD25+ T cells from baseline to time of OFC

PBMCs were stimulated with crude peanut extract and tetanus toxin for 7 days, and then stained for Treg markers. Individual subjects are shown for (a) peanut OIT and (b) placebo groups. *p=0.04.