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

• Published in: Journal of allergy and clinical immunology Vol. 139; no. 1; pp. 173 - 181.e8
• Main Authors: Vickery, Brian P., Berglund, Jelena P., Burk, Caitlin M., Fine, Jason P., Kim, Edwin H., Kim, Jung In, Keet, Corinne A., Kulis, Michael, Orgel, Kelly G., Guo, Rishu, Steele, Pamela H., Virkud, Yamini V., Ye, Ping, Wright, Benjamin L., Wood, Robert A., Burks, A. Wesley
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017; Elsevier Limited
• Subjects: Allergens - immunology; Allergy and Immunology; Antigens, Plant - immunology; Arachis - immunology; Asthma; Child, Preschool; Clinical trials; desensitization; Desensitization, Immunologic; Double-Blind Method; Early intervention; Female; Food; Food allergies; Humans; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunotherapy; Infant; Male; Oral immunotherapy; peanut allergy; Peanut Hypersensitivity - blood; Peanut Hypersensitivity - therapy; Peanuts; Pediatrics; Plant Proteins - immunology; Proteins; randomized clinical trial; sustained unresponsiveness; SU; 4-SU; AE; early intervention; ITT; randomized clinical trial; IQR; LEAP; OFC; Oral immunotherapy; desensitization; peanut allergy; E-OIT; SPT; sustained unresponsiveness; psIgG4; OIT; psIgE; DBPCFC; psIgG 4; Learning Early About Peanut Allergy; Intent-to-treat; Peanut-specific IgG 4; Oral food challenge; Adverse event; Skin prick test; Interquartile range; Double-blinded, placebo-controlled food challenge; Early intervention oral immunotherapy; Peanut-specific IgE; Sustained unresponsiveness at 4 weeks after stopping early intervention oral immunotherapy
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2016.05.027

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. We sought to test the safety, effectiveness, and feasibility of early OIT (E-OIT) in the treatment of peanut allergy. 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. 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. 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.